ABSTRACT
Amino acids, metabolized by host cells as well as commensal gut bacteria, have signaling effects on host metabolism. Oral supplementation of the essential amino acid histidine has been shown to exert metabolic benefits. To investigate whether dietary histidine aids glycemic control, we performed a case-controlled parallel clinical intervention study in participants with type 2 diabetes (T2D) and healthy controls. Participants received oral histidine for seven weeks. After 2 weeks of histidine supplementation, the microbiome was depleted by antibiotics to determine the microbial contribution to histidine metabolism. We assessed glycemic control, immunophenotyping of peripheral blood mononucelar cells (PBMC), DNA methylation of PBMCs and fecal gut microbiota composition. Histidine improves several markers of glycemic control, including postprandial glucose levels with a concordant increase in the proportion of MAIT cells after two weeks of histidine supplementation. The increase in MAIT cells was associated with changes in gut microbial pathways such as riboflavin biosynthesis and epigenetic changes in the amino acid transporter SLC7A5. Associations between the microbiome and MAIT cells were replicated in the MetaCardis cohort. We propose a conceptual framework for how oral histidine may affect MAIT cells via altered gut microbiota composition and SLC7A5 expression in MAIT cells directly and thereby influencing glycemic control. Future studies should focus on the role of flavin biosynthesis intermediates and SLC7A5 modulation in MAIT cells to modulate glycemic control.
Subject(s)
Diabetes Mellitus, Type 2 , Gastrointestinal Microbiome , Histidine , Mucosal-Associated Invariant T Cells , Humans , Histidine/metabolism , Diabetes Mellitus, Type 2/microbiology , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/immunology , Gastrointestinal Microbiome/drug effects , Middle Aged , Male , Female , Mucosal-Associated Invariant T Cells/immunology , Mucosal-Associated Invariant T Cells/metabolism , Glycemic Control , Dietary Supplements , Case-Control Studies , Feces/microbiology , Blood Glucose/metabolism , Aged , Adult , Bacteria/classification , Bacteria/metabolism , Bacteria/genetics , Administration, Oral , DNA MethylationABSTRACT
The phenomenon of microbial resistance and its resulting biofilms to traditional antibiotics is worsening over time. Therefore, the discovery of alternative substances that inhibit microbial activities through mechanisms different from those of known antibiotics requires attention. So, chitosan was crosslinked using different amounts of oxalyl dihydrazide yielding four novel hydrogels; ODHCs-I, ODHCs-II, ODHCs-III, and ODHCs-IV of crosslinking degree 12.17, 20.67, 31.67, and 43.17, respectively. Different amounts of CuO nanoparticles were impregnated into ODHCs-IV, obtaining ODHCs-IV/CuONPs-1 %, ODHCs-IV/CuONPs-3 % and ODHCs-IV/CuONPs-5 % composites. Their structure was emphasized using FTIR, SEM, XRD, TEM, EDX and elemental analysis. Their in vitro antimicrobial and anti-biofilm activities improved with increasing ODH and CuONPs content. ODHCs-IV exhibited minimal inhibition concentration (2 µg/mL) against S. pyogenes that was much lower than Vancomycin (3.9 µg/mL). ODHCs-IV/CuONPs-5 % displayed better inhibition performance than Vancomycin and Amphotericin B against Gram-positive-bacteria and fungi, respectively, and comparable one to that of Vancomycin against Gram-negative-bacteria. ODHCs-IV/CuONPs-5 % displayed much lower minimal biofilm inhibition concentrations (1.95 to 3.9 µg/mL) as compared with those of ODHCs-IV (7.81 and 15.63 µg/mL), against C. albicans, S. pyogenes, and K. pneumonia. ODHCs-IV/CuONPs-5 % composite is safe on normal human cells. Oxalyl dihydrazide and CuONPs amalgamated into chitosan in one formulation promoted its antimicrobial efficiency.
Subject(s)
Biofilms , Chitosan , Copper , Hydrogels , Microbial Sensitivity Tests , Nanocomposites , Chitosan/chemistry , Chitosan/pharmacology , Copper/chemistry , Hydrogels/chemistry , Hydrogels/pharmacology , Hydrogels/chemical synthesis , Nanocomposites/chemistry , Biofilms/drug effects , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Anti-Infective Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Chemistry Techniques, Synthetic , HumansABSTRACT
Sonchus oleraceus L. is a leafy vegetable that is usually consumed in the area of the Mediterranean and is a frequently used traditional herb to treat a variety of ailments. Previous studies deduced the potent antioxidant and cytotoxic functions of the different extracts and isolated compounds from S. oleraceus. The current study represents the first instance of chemical profiling and bioactivities of the extracted essential oil (EO) of S. oleraceus. The present investigation set out to identify the chemical components of this EO by means of Gas Chromatography with Flame Ionization Detector (GC-FID) and Gas Chromatography-Mass Spectrometry (G004-MS) techniques; assess the oil's antioxidant potencies through 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate (ABTS) assays; and evaluate the oil's cytotoxic impact against HepG2 cancer cell lines. The GC-MS chemical profiling revealed the identification of 23 components representing 97.43% of the total oil mass within abundant cyclic ketones (20.15%), nonterpenoidial hydrocarbons (28.77%), and sesquiterpenes (42.19%). The main components were n-nonadecane (28.77%), trans-caryophyllene (23.73%), trans-methyl dihydrojasmonate (19.55%), and cis-cadina-1,4-diene (9.44%). In a dose-dependent manner, this EO demonstrated antioxidant capacities on DPPH and ABTS, with IC50 values of 609.35 and 804.16 µg/mL, respectively, compared to ascorbic acid. Using doxorubicin as a reference therapy, the MTT assay findings revealed that this oil had remarkable inhibitory effects on the proliferation of HepG2 cancer cell lines, with an IC50 of 136.02 µg/mL. More studies were recommended for further investigation of new biological roles for this oil and its main components, along with the construction of action mechanisms based on chemical components.
ABSTRACT
Although various approaches exist for treating cancer, chemotherapy continues to hold a prominent role in the management of this disease. Besides, microtubules serve as a vital component of the cellular skeleton, playing a pivotal role in the process of cell division making it an attractive target for cancer treatment. Hence, the scope of this work was adapted to design and synthesize new anti-tubulin tetrabromophthalimide hybrids (3-17) with colchicine binding site (CBS) inhibitory potential. The conducted in vitro studies showed that compound 16 displayed the lowest IC50 values (11.46 µM) at the FaDu cancer cell lines, whereas compound 17 exhibited the lowest IC50 value (13.62 µM) at the PC3 cancer cell line. However, compound 7b exhibited the lowest IC50 value (11.45 µM) at the MDA-MB-468 cancer cell line. Moreover, compound 17 was observed to be the superior antitumor candidate against all three tested cancer cell lines (MDA-MB-468, PC3, and FaDu) with IC50 values of 17.22, 13.15, and 13.62 µM, respectively. In addition, compound 17 showed a well-established upregulation of apoptotic markers (Caspases 3, 7, 8, and 9, Bax, and P53). Moreover, compound 17 induced downregulation of the antiapoptotic markers (MMP2, MMP9, and BCL-2). Furthermore, the colchicine binding site inhibition assay showed that compounds 15a and 17 exhibited particularly significant inhibitory potentials, with IC50 values of 23.07 and 4.25 µM, respectively, compared to colchicine, which had an IC50 value of 3.89 µM. Additionally, cell cycle analysis was conducted, showing that compound 17 could prompt cell cycle arrest at both the G0-G1 and G2-M phases. On the other hand, a molecular docking approach was applied to investigate the binding interactions of the examined candidates compared to colchicine towards CBS of the ß-tubulin subunit. Thus, the synthesized tetrabromophthalimide hybrids can be regarded as outstanding anticancer candidates with significant apoptotic activity.
Subject(s)
Antineoplastic Agents , Apoptosis , Drug Design , Phthalimides , Tubulin Modulators , Humans , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor , Molecular Docking Simulation , Phthalimides/chemical synthesis , Phthalimides/pharmacology , Structure-Activity Relationship , Tubulin/metabolism , Tubulin Modulators/chemical synthesis , Tubulin Modulators/pharmacologyABSTRACT
The catalytic activity of chitosan (Cs) and grafted Cs led to the preparation of terephthalohydrazide Cs Schiff's base hydrogel (TCsSB), which was then investigated as an eco-friendly biocatalyst for synthesizing novel thiazole derivatives. TCsSB exhibited greater surface area and higher thermal stability compared to Cs, making it a promising eco-friendly biocatalyst. We synthesized two novel series of thiazoles via the reaction of 2-(2-oxo-1,2-diphenylethylidene) hydrazine-1-carbothioamide with various hydrazonoyl chlorides and 2-bromo-1-arylethan-1-ones, employing ultrasonic irradiation and using TCsSB as a catalyst. A comparative study between Cs and TCsSB revealed higher yields than TCsSB. The methodology offered advantages such as mild reaction conditions, quick reaction times, and high yields. TCsSB could be reused multiple times without a significant loss of potency. The chemical structures of the newly synthesized compounds were verified through IR, 1H NMR, 13C NMR, and MS analyses. Six synthesized compounds were assessed for their in vitro antibacterial effectiveness by establishing the minimum inhibitory concentration against four distinct bacterial strains. The docking analyses revealed favorable binding scores against several amino acids within the selected protein (PDB Code-1MBT) for these compounds, with compound 4c exhibiting particularly noteworthy binding properties. Additionally, the in silico ADME parameter estimation for all compounds indicated favorable pharmacological properties for these compounds.
ABSTRACT
Background: Interprofessional education (IPE) and interprofessional collaborative practice (IPCP) were developed to address the health needs of communities through collaborative practice across healthcare disciplines. The impact of IPE on IPCP and clinical service delivery in South Africa is not evident, possibly because of the lack of IPCP experiences among healthcare professionals. Aim: International literature reports facilitators and barriers of IPCP implementation, but there was a need to filter the evidence to identify literature from the South African context regarding the perceptions of healthcare workers' perceived barriers and facilitators of IPCP. Setting: South African literature. Methods: A systematic review was conducted to synthesise evidence from articles published between January 2017 and December 2021. Only qualitative studies targeting health professionals in South Africa who had been exposed to IPCP were included. Consistent with Preferred Reporting Items for Systematic reviews and Meta-Analysis, a multi-database search yielded 424 articles, which were screened for relevance and appraised for quality using the Critical Appraisal Skills Programme (CASP) tool. A thematic synthesis of the findings was conducted by applying ethical principles. Results: Synthesis of barriers and enablers for IPCP implementation in the South African context included key aspects of healthcare systems, management and team leadership. Conclusion: The integration of IPCP into clinical practice in South Africa is still limited as healthcare professionals operate in silos. Contribution: Recommendations of this study include greater integration of services combined with competent management and visionary leadership, together with the incorporation of IPE into undergraduate professional training programmes.
ABSTRACT
INTRODUCTION: Antiandrogen therapy can reduce the expression of transmembrane protease 2, which is essential for severe acute respiratory syndrome coronavirus-2 to enter the host cells. Prior trials suggested the efficacy of antiandrogen agents in patients with COVID-19. We investigated whether antiandrogen agents reduce mortality compared to placebo or usual care. EVIDENCE ACQUISITION: We searched for randomized controlled trials comparing antiandrogen agents with placebo or usual care alone in adults with COVID-19 in PubMed, EMBASE, the Cochrane Library, the reference lists of retrieved articles, and publications by manufacturers of antiandrogen agents. The primary outcome was mortality at the longest follow-up available. The secondary outcomes included clinical worsening, the need for invasive mechanical ventilation, admission to the intensive care unit, hospitalization, and thrombotic events. We registered this systematic review and meta-analysis in PROSPERO International Prospective Register of Systematic Reviews (CRD42022338099). EVIDENCE SYNTHESIS: We included 13 randomized controlled trials enrolling 1934 COVID-19 patients. We found that antiandrogen agents reduced mortality at the longest follow-up available (91/1021 [8.9%] vs. 245/913 [27%]; risk ratio =0.40; 95% confidence interval, 0.25-0.65; P=0.0002; I2=54%). Antiandrogen therapy also reduced clinical worsening (127/1016 [13%] vs. 298/911 [33%]; risk ratio =0.44; 95% confidence interval, 0.27-0.71; P=0.0007; I2=70%) and hospitalization (97/160 [4.4%] vs. 24/165 [15%]; risk ratio =0.24; 95% confidence interval, 0.10-0.58; P=0.002; I2=44%). There was no significant difference in the other outcomes between the two treatment groups. CONCLUSIONS: Antiandrogen therapy reduced mortality and clinical worsening in adult patients with COVID-19.
Subject(s)
COVID-19 , Adult , Humans , Randomized Controlled Trials as Topic , Systematic Reviews as Topic , Respiration, Artificial , Androgen Antagonists/therapeutic useABSTRACT
In our previous work, three different weight ratios of chitosan/PVA (1:3, 1:1, and 3:1) were blended and then cross-linked with trimellitic anhydride isothiocyanate (TAI) at a concentration depending on their chitosan content, obtaining three hydrogels symbolized by H13, H11, and H31. Pure chitosan was cross-linked with TAI, producing a hydrogel symbolized by H10. Further, three H31-based silver nanoparticles composites (H31/AgNPs1%, H31/AgNPs3%, and H31/AgNPs5%) were also synthesized. They were investigated, for the first time in this study, as adsorbents for Congo Red (CR) and Crystal Violet (CV) dyes. The removal efficiency of CR dye increased with increasing H10 content in the hydrogels, and with increasing AgNP content in the composites, reaching 99.91% for H31/AgNPs5%. For CV dye, the removal efficiency increased with the increase in the PVA content. Furthermore, the removal efficiency of CV dye increased with an increasing AgNP content, reaching 94.7% for H31/AgNPs5%. The adsorption capacity increased with the increase in both the initial dye concentration and temperature, while with an increasing pH it increased in the case of CV dye and decreased in the case of CR dye. The adsorption of CV dye demonstrated that the Freundlich isotherm model is better suited for the experimental results. Moreover, the results were best fitted with pseudo-second-order kinetic model.
ABSTRACT
Background: Child neglect is a public health, human rights, and social problem, with potentially devastating and costly consequences. The aim of this study was to: (1) summarize the oral health profile of children across the globe; (2) provide a brief overview of legal instruments that can offer children protection from dental neglect; and (3) discuss the effectiveness of these legal instruments. Methods: We summarized and highlighted the caries profile and status of implementation of legislation on child dental neglect for 26 countries representing the World Health Organization regions: five countries in Africa (Nigeria, South Africa, Sudan, Tanzania, Zimbabwe), eight in the Americas (Argentina, Brazil, Canada, Chile, Mexico, Peru, Unites States of America, Uruguay), six in the Eastern Mediterranean (Egypt, Iran, Libya, Jordan, Qatar, Saudi Arabia), four in Europe (Italy, Latvia, Serbia, United Kingdom), two in South-East Asia (India and Indonesia) and one country (China) with its special administrative region (Hong Kong) in the Western Pacific. Results: Twenty-five of the 26 countries have legal instruments to address child neglect. Only two (8.0%) of these 25 countries had specific legal instruments on child dental neglect. Although child neglect laws can be interpreted to establish a case of child dental neglect, the latter may be difficult to establish in countries where governments have not addressed barriers that limit children's access to oral healthcare. Where there are specific legal instruments to address child dental neglect, a supportive social ecosystem has also been built to facilitate children's access to oral healthcare. A supportive legal environment, however, does not seem to confer extra protection against risks for untreated dental caries. Conclusions: The institution of specific country-level legislation on child dental neglect may not significantly reduce the national prevalence of untreated caries in children. It, however, increases the prospect for building a social ecosystem that may reduce the risk of untreated caries at the individual level. Social ecosystems to mitigate child dental neglect can be built when there is specific legislation against child dental neglect. It may be more effective to combine public health and human rights-based approaches, inclusive of an efficient criminal justice system to deal with child dental neglect.
ABSTRACT
For chemical modification, p-aminobenzoic acid was incorporated into chitosan Schiff base (ACsSB) and chitosan (ACs). Two ACs-based CuO nanoparticles composites; ACs/CuONPs-1 % and ACs/CuONPs-5 %, were also synthesized. Their structures were emphasized utilizing several analytical techniques; elemental analysis, FTIR, 1H NMR, XRD, SEM, EDX and TEM. Compared with standard cyclooxygenase (COX) inhibitor, Celecoxib, the prepared biomaterials showed in vitro selective inhibitory effectiveness against COX-2 enzyme that could be sorted, according to their MIC values that produce 50 % inhibition of COX-2 enzyme activity, as follows: Celecoxib (0.28 µg/mL) > ACs/CuONPs-5 % (4.1 µg/mL) > ACs/CuONPs-1 % (14.8 µg/mL) > ACs (38.5 µg/mL) > ACsSB (58.9 µg/mL) > chitosan (>125 µg/mL). Further, ACs/CuONPs-5 % has more in vitro inhibition efficiency towards Helicobacter pylori (H. pylori) than the other prepared biomaterials. Interestingly, the MIC value of 100 % growth inhibition of H. pylori for ACs/CuONP-5 % is equal to that of drug Clarithromycin (1.95 µg/mL). Thus, ACs/CuONPs-5 % has a promising potential as anti-H. pylori and selective anti-inflammatory agent. ACs/CuONPs-5 % is safe on the human gastric normal cells (GES-1). Therefore, amalgamation of both p-aminobenzoic acid and CuONPs into chitosan extremely promoted its anti-inflammatory and anti-H. pylori activity. This is a promising approach to achieve methods successful to compete the conventional antibiotics.
Subject(s)
Chitosan , Helicobacter pylori , Metal Nanoparticles , Nanoparticles , Humans , Chitosan/pharmacology , Chitosan/chemistry , Biocompatible Materials/pharmacology , Copper/pharmacology , Copper/chemistry , 4-Aminobenzoic Acid , Celecoxib , Cyclooxygenase 2 , Nanoparticles/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Inflammatory Agents , Oxides , Metal Nanoparticles/chemistryABSTRACT
Unintended side effects linked to the antineoplastic drug cisplatin are a major drawback in its clinical application. The underlying source of these side effects include the generation of reactive oxygen species which are toxic and damaging to tissues and organs. In the present study the anti-inflammatory and antioxidant potential of sodium salicylate was assessed against cisplatin-induced hepatotoxicity in albino rats. Sodium salicylate was used as a model drug and loading into hollow structured porous silica using ultrasound-assisted sol-gel method to produce a nanoemulsion. Transmission Electron Microscopy and Dynamic Light scattering analysis were employed to assess the structural properties and stability of this model. Liver function was assessed by measuring biomarkers including ALT, AST & GGT and oxidant/antioxidant markers including MDA, NO, PON, GSH, MCP1 & AVP in serum or liver tissue. Additionally, blood leukocyte DNA damage was evaluated. Cisplatin significantly altered the normal levels of all biomarkers confirming its hepatotoxic effects. In contrast, treatment with sodium salicylate-loaded silica nanoemulsion significantly restored the levels of these markers. The finding suggests the protective effects of this model drug in preventing cisplatin-induced hepatotoxicity, and therefore may have implications in attenuating cisplatin-induced hepatotoxicity.
Subject(s)
Antineoplastic Agents , Chemical and Drug Induced Liver Injury , Drug-Related Side Effects and Adverse Reactions , Nanoparticles , Rats , Animals , Cisplatin/toxicity , Antioxidants/pharmacology , Antioxidants/metabolism , Sodium Salicylate/metabolism , Sodium Salicylate/pharmacology , Oxidative Stress , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/prevention & control , Chemical and Drug Induced Liver Injury/drug therapy , Antineoplastic Agents/toxicity , Liver/metabolism , Drug-Related Side Effects and Adverse Reactions/metabolism , Biomarkers/metabolismABSTRACT
Two novel chemically cross-linked chitosan hydrogels were successfully prepared via insertion of oxalyl dihydrazide moieties between chitosan Schiff's base chains (OCsSB) and between chitosan chains (OCs). For more modification, two different concentrations of ZnO nanoparticles (ZnONPs) were loaded into OCs to obtain OCs/ZnONPs-1 % and OCs/ZnONPs-3 % composites. The prepared samples were recognized using elemental analyses, FTIR, XRD, SEM, EDS and TEM. Their inhibitory action against microbes and biofilms were classified as: OCs/ZnONPs-3 % > OCs/ZnONPs-1 % > OCs > OCsSB > chitosan. OCs has inhibition activity similar to Vancomycin of minimum inhibitory concentration (MIC) value of 3.9 µg/mL against P. aeruginosa. OCs exhibited minimum biofilm inhibitory concentration (MBIC) values (from 31.25 to 62.5 µg/mL) less than that of OCsSB (from 62.5 to 250 µg/mL) which lower than that of chitosan (from 500 to 1000 µg/mL) against S. epidermidis, P. aeruginosa and C. albicans. OCs/ZnNPs-3 % showed MIC value (that caused 100 % inhibition of Clostridioides difficile, C. difficile) of 0.48 µg/mL much lower than Vancomycin (1.95 µg/mL). Both OCs and OCs/ZnONPs-3 % composite were safe on normal human cells. Thus, inclusion of oxalyl dihydrazide and ZnONPs into chitosan greatly reinforced its antimicrobial activity. This is a good strategy to accomplish adequate systems for competing traditional antibiotics.
Subject(s)
Chitosan , Clostridioides difficile , Nanoparticles , Zinc Oxide , Humans , Zinc Oxide/pharmacology , Chitosan/pharmacology , Vancomycin/pharmacology , Hydrogels , Anti-Bacterial Agents/pharmacology , BiofilmsABSTRACT
A new hydrogel, based on chitosan crosslinked with 2-chlorophenyl-bis(6-amino-1,3-dimethyluracil-5-yl) methane, (2Clph-BU-Cs), has been successfully created. Various instrumental techniques such as elemental analysis, FTIR, SEM, and XRD were used to prove its structure. Its removal efficiency for anionic Congo red (CR) dye under different conditions for industrial wastewater treatment was studied. For optimizing the conditions to maximize CR dye removal, the impacts of temperature, contact time, pH, and initial concentration of the dye on adsorption capacity were investigated. The removal of the dye was pH-dependent, with a much higher value achieved at pH 4 than at pH 7 and 9. The maximum adsorption capacity of the hydrogel was 93.46 mg g-1. The model of adsorption process was fitted to the pseudo-second-order kinetic model. The intraparticle diffusion demonstrated the multi-step nature of the adsorption process. The thermodynamic results showed that the adsorption process was endothermic because of the positive value of enthalpy (43.70 kJ mol-1). The process of adsorption at high temperatures was spontaneous, according to the values of ∆G0. An increase in randomness was seen in the value of ∆S°. Generally, the investigated hydrogel has the potential to be used as a promising effective reusable adsorbent for industrial wastewater remediation.
ABSTRACT
A new series of hydrogels was successfully prepared by incorporating various substituted bisuracil (R-BU) linkages between chitosan Schiff's base chains (R-BU-CsSB) and between chitosan chains (R-BU-Cs). After protection of the amino groups of chitosan by benzaldehyde, yielding chitosan Schiff's base (CsSB), the reaction with epichlorohydrin was confined on the -OH on C6 to produce epoxy chitosan Schiff's base (ECsSB), which was reacted with R-BU to form R-BU-CsSB hydrogels, and finally, the bioactive amino groups of chitosan were restored to obtain R-BU-Cs hydrogels. Further, some R-BU-Cs-based ZnO nanoparticle (R-BU-Cs/ZnONPs) composites were also prepared. Appropriate techniques such as elemental analysis, FTIR, XRD, SEM, and EDX were used to verify their structures. Their inhibition potency against all the tested microbes were arranged as: ZnONPs bio-composites > R-BU-Cs hydrogels > R-BU-CsSB hydrogels > Cs. Their inhibition performance against Gram-positive bacteria was better than Gram-negative ones. Their minimum inhibitory concentration (MIC) values decreased as a function of the negative resonance effect of the substituents in the aryl ring of R-BU linkages in the hydrogels. Compared with Vancomycin, the ZnONPs bio-composites showed superior inhibitory effects against most of the tested Gram-negative bacteria, all inspected Gram-positive ones, and all investigated fungi.
ABSTRACT
In situ investigations of cracks propagating at up to 2.5â kmâ s-1 along an (001) plane of a silicon single crystal are reported, using X-ray diffraction megahertz imaging with intense and time-structured synchrotron radiation. The studied system is based on the Smart Cut process, where a buried layer in a material (typically Si) is weakened by microcracks and then used to drive a macroscopic crack (10-1â m) in a plane parallel to the surface with minimal deviation (10-9â m). A direct confirmation that the shape of the crack front is not affected by the distribution of the microcracks is provided. Instantaneous crack velocities over the centimetre-wide field of view were measured and showed an effect of local heating by the X-ray beam. The post-crack movements of the separated wafer parts could also be observed and explained using pneumatics and elasticity. A comprehensive view of controlled fracture propagation in a crystalline material is provided, paving the way for the in situ measurement of ultra-fast strain field propagation.
ABSTRACT
Novel hydrogels were prepared by blending chitosan and poly(vinyl alcohol), PVA, then crosslinking the resulting blends using trimellitic anhydride isothiocyanate at a concentration based on chitosan content in the blends. The weight ratios of chitosan: PVA in the blends were 1:3, 1:1, and 3:1 to produce three hydrogels symbolized as H13, H11, and H31, respectively. For a comparison, H10 was also prepared by crosslinking pure chitosan with trimellitic anhydride isothiocyanate. For further modification, three H31/silver nanocomposites (AgNPs) were synthesized using three different concentrations of silver nitrate to obtain H31/AgNPs1%, H31/AgNPs3% and H31/AgNPs5%. The structures of the prepared samples were emphasized using various analytical techniques. PVA has no inhibition activity against the tested microbes and biofilms. The antimicrobial and anti-biofilm formation activities of the investigated samples was arranged as: H31/AgNPs5% ≥ H31/AgNPs3% > H31/AgNPs1% > H10 > H31 > H11 > H13 > chitosan. H31/AgNPs5% and H31/AgNPs3% were more potent than Vancomycin and Amphotericin B against most of the tested microbes. Interestingly, H31 and H31/AgNPs3% were safe on the normal human cells. Consequently, hydrogels resulting from crosslinked blends of chitosan and PVA loaded with AgNPs in the same structure have significantly reinforced the antimicrobial and inhibition activity against the biofilms of PVA.
ABSTRACT
Cisplatin (Cisp) is a widely distributed chemotherapeutic drug for cancers. Nephrotoxicity is one of the most common side effects of the use of this drug. Carvacrol (CV) is a common natural compound in essential oils and extracts of medicinal plants with potent in vivo and in vitro bioactivities. The work was extended to achieve the target of investigation of the protective potentialities of CV and its nanoemulsion as a cytoprotective drug against Cisp-induced nephrotoxicity in albino rats. CV-nanoemulsion was prepared by a hydrophilic surfactant polysorbate 80 (Tween 80) and deionized water. The TEM image of the particle distribution prepared nanoemulsion is mainly spherical in shape with particle size varying between 14 and 30 nm. Additionally, the Cisp administration caused the increasing of the levels of urea and creatinine in the blood and serum. These increasing of urea and creatinine levels caused consequently the turbulence of the oxidative stress as well as the rising of hs-CRP, IL-6, and TNF-α levels in the serum. Also, histopathological changes of the kidney tissue were observed. These changes back to normal by treatment with CV-nanoemulsion. Expression levels of nephrotoxicity-related genes including LGALS3, VEGF, and CAV1 in kidney tissue using qRT-PCR were measured. The results revealed that the expression of LGALS3, VEGF and CAV1 genes was highly significantly increased in only Cisp treated group when compared with other treated groups. While, these genes expressions were significantly decreased in Cisp + CV treated group when compared with Cisp treated rats (P < 0.001). In addition, there were no significant differences between Cisp + nano-CV treated group and both negative control and nanoemulsion alone groups but it was not significant. In addition, the Western blot of protein analysis results showed that the LGALS3 and CAV1 are highly expressed only in Cisp + CV treated group compared with other groups. There was no significant difference between Cisp + nano-CV treated animals and negative control for both mRNA and protein expression. Based on these results, CV was combined with calcium alginate; a more stable capsule is formed, allowing for the formation of a double wall in the microcapsule. These results supported the therapeutic effect of CV and its nano-emulsion as cytoprotective agents against Cisp nephrotoxicity.
ABSTRACT
Two novel chitosan derivatives were prepared by incorporating salicylhydrazide into chitosan Schiff base (SCsSB) and chitosan (SCs). Two nanocomposites, SCs/TiO2-1% and SCs/TiO2-3%, were also prepared. Their structures were confirmed using elemental analyses, FTIR, XRD, SEM, EDX and TEM. Their antimicrobial and anti-biofilm activities were arranged as: SCs/TiO2-3% > SCs/TiO2-1% > SCs > SCsSB > chitosan. SCs showed minimum inhibitory concentration (MIC) value of 1.95 µg/mL against A. niger which was comparable with that of Amphotericin B. SCs/TiO2-3% showed higher inhibition against S. epidermidis, S. aureus, S. pyogenes, P. aeruginosa and E. coli than Vancomycin. While, it showed comparable inhibition activity to that of Vancomycin against B. subtilis and P. mirabilis. SCs/TiO2-3% showed MIC values equal 0.48 and 0.98 µg/mL corresponded to 0.98 and 1.95 µg/mL of Amphotericin B against C. albicans, A. fumigatus and A. niger, respectively. SCs/TiO2-3% showed much lower minimum biofilm inhibitory concentration (MBIC) values, ranged between 1.95 and 7.81 µg/mL, than those of SCs, ranged from 62.5 to 125 µg/mL. SCs/TiO2-3% was safe on normal human cells. The modifiers and TiO2 nanoparticles incorporated into chitosan in one structure developed its performance. It is approach for attaining appropriate structures which are good competitors for antimicrobial agents.
Subject(s)
Anti-Infective Agents , Chitosan , Nanoparticles , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Biofilms , Chitosan/chemistry , Chitosan/pharmacology , Escherichia coli , Humans , Microbial Sensitivity Tests , Nanoparticles/chemistry , Staphylococcus aureus , Titanium/chemistry , Titanium/pharmacologyABSTRACT
Novel Uracil-modified chitosan (UCs) adsorbent has successfully been synthesized through a four-step method during which the amino groups of chitosan have been protected, then epoxy nuclei have been incorporated, afterwards the latter have been opened using 6-amino-1,3-dimethyl uracil, and finally the amino groups have been regained via removing the protection. Its structure was checked using FTIR, XRD and SEM techniques. The adsorption capacity of UCs for anionic Congo Red (CR) dye was studied under various conditions. It decreased significantly with increasing the solution pH value and dye concentration, while increased with increasing temperature. The adsorption of UCs for CR dye at different temperatures, solution pH and dye concentrations fitted to the kinetic model of pseudo-second order and Elovich model. The intraparticle diffusion model showed that the adsorption process involves multi-step process. The isotherm of CR dye adsorption by UCs conforms to the Langmuir isotherm model indicating the monolayer nature of adsorption. The maximum monolayer coverage capacity, qmax, was 434.78 mg g-1. Studying the thermodynamic showed that the adsorption of CR dye onto UCs was endothermic as illustrated from the positive value of enthalpy (21.37 kJ mol-1). According to the values of ΔG°, the adsorption process was spontaneous at all selected temperatures. The value of ΔS° showed an increase in randomness for the adsorption of CR dye by UCs. The value of activation energy was 18.40 kJ mol-1.
ABSTRACT
OBJECTIVE: Investigation of the prevalence of oral mucosal lesions in human immunodeficiency virus (HIV)-infected children undergoing highly active antiretroviral therapy (HAART). MATERIALS AND METHODS: Cross-sectional study of 66 HIV seropositive children, comprised of 28 (42.4%) females and 38 (57.6%) males (average age of 6 years). Study participants all required data regarding CD4+ T-helper cell counts and the viral load. All participants underwent an orofacial clinical examination by calibrated clinicians. Associations between the presence of oral mucosal lesions, CD4+ cell counts, and viral load were analyzed using Poisson regression. RESULTS: The prevalence of oral manifestations was detected in 21 children (31.8%). Oral lesions were detected in 16 children with viral load copies <50 cells/mm3 and 22 children with CD4+ counts >500 cells/mm3 . Predominant lesions identified included angular cheilitis (36.7%), candidiasis (13.3%) and atypical oral ulcers (13.3%). The presence of one lesion was the most prevalent represented by 19 children. Oral lesions in relation to the CD4+ counts >500 resulted in; 14 children with one oral lesion, 5 with two lesions and 3 with three oral mucosal lesions. The other half of this CD4+ count patient group presented with no oral mucosal lesions. Oral lesions in relation Viral load copies <50 resulted in; 9 children with one oral lesion, 3 with two oral mucosal lesions and 4 with three oral mucosal lesions. The other half of this Viral load patient group presented with no oral mucosal lesions. No significant correlations were established between the presence of oral mucosal lesions and low CD4+ counts (p = 0.715) nor with high viral load counts (p = 0.638). CONCLUSION: HIV-related oral mucosal lesions still presented in the participants despite management with HAART. Based on the results, CD4+ counts and viral load does not appear to be suitable markers of orofacial involvement in children.