Search Results (28)

Neurodegenerative diseases (NDs) pose a major challenge to global healthcare systems owing to their devastating effects and limited treatment options. These disorders are characterized by progressive loss of neuronal structure and function, resulting in cognitive and motor impairments. Current therapies primarily focus on symptom management rather than on targeting the underlying causes. However, clustered regularly interspaced short palindromic repeat (CRISPR) technology offers a promising alternative by enabling precise genetic modifications that could halt or even reverse ND progression. CRISPR-Cas9, the most widely used CRISPR system, acts as a molecular scissor targeting specific DNA sequences for editing. By designing guide RNAs (gRNAs) to match sequences in genes associated with NDs, researchers can leverage CRISPR to knockout harmful genes, correct mutations, or insert protective genes. This review explores the potential of CRISPR-based therapies in comparison with traditional treatments for NDs. As research advances, CRISPR has the potential to revolutionize ND treatment by addressing its genetic underpinnings. Ongoing clinical trials and preclinical studies continue to expand our understanding and application of this powerful tool to fight debilitating conditions. Full article

Intracanal medicaments are an important adjunct to the effective disinfection of the root canal system. However, conventional intracanal medicaments do not provide adequate protection against Enterococcus faecalis, which is the organism of interest in many cases of root canal failures. This study aimed to evaluate the influence of biosynthesized calcium oxide nanoparticles (CaO NPs) on the antibacterial activity, pH, microleakage and cytotoxicity of intracanal medicaments. CaO NPs were biosynthesized by the direct thermal decomposition of eggshells (EGS) and the reduction of calcium nitrate with papaya leaf extract (PLE). These nanoparticles were mixed with a proprietary calcium hydroxide powder in 10% and 25% (w/w) concentrations and blended in analytical-grade coconut oil to formulate the experimental medicaments. These were then evaluated for antibacterial activity, pH, microleakage and cytotoxicity at 1 day, 7 days and 15 days. A proprietary calcium hydroxide paste formulation (MX) was used as the control. Means and standard deviations were calculated and analyzed using repeated-measures ANOVA for pH and three-way ANOVA for the antibacterial effect, microleakage and cytotoxicity, followed by LSD post hoc analysis. Significant antibacterial activity was noted against Enterococcus faecalis at all times, with zones of inhibition (ZOI) up to 19.60 ± 2.30 mm. pH levels up to 13.13 ± 0.35 were observed for the experimental groups. Microleakage remained comparable to the control, while cytotoxicity was not observed in any of the groups at any time. Intracanal medicaments formulated with 10% and 25% (w/w) of biosynthesized CaO NPs could be promising candidates for the disinfection of the root canal system compared to conventional counterparts. Full article

Reverse logistics is a known supply chain practice and has been proven effective in recent decades. In developing countries, these practices are already employed and considered beneficial for the business or firms. The reverse logistics concept creates value for customers and firms. Considering this, this study intends to highlight reverse logistics practices in Pakistan and examine the reverse logistics impacts on competitive advantage with the mediating role of the firm’s organizational performance in Pakistan’s manufacturing industries. In this study, plastic bottle manufacturing firms working in Pakistan were selected to collect the data. Hence, to collect the data from these firms, a survey technique was sought to determine the impact of reverse logistic practices on competitive advantage with the mediating role of organizational performance. A structured and adapted questionnaire was used in this regard. Organizational performance was assumed as the operational and financial performance of these firms. Data were collected using a convenience sampling technique, and the targeted population was the middle-level employees of bottle manufacturing firms. The statistical tool was adopted as the study was quantitative, and results were extracted numerically. IBM SPSS and AMOS version 24 were used as supporting statistical analysis and interpretation tools. Data analysis demonstrated that out of 219 respondents, 68 were supervisors, and others were middle managers. Statistics show that most females were supervisors, and most males were middle managers. “Confirmatory Factor Analysis (CFA)” was performed to examine the fit of the three-factor model, showing good fit indices (Chi-square/df = 2.71, CFI = 0.902, TLI = 0.896, RMSEA = 0.081), which indicates that the model fits the data well. According to the study’s findings, a significant impact was examined between reverse logistics and competitive advantage, and a mediating role was confirmed between those variables. This study poses unique strengths in theoretical and practical ways and helped enrich the available literature and findings. Full article

Water monitor lizards (WMLs) reside in unhygienic and challenging ecological surroundings and are routinely exposed to various pathogenic microorganisms. It is possible that their gut microbiota produces substances to counter microbial infections. Here we determine whether selected gut bacteria of water monitor lizards (WMLs) possess anti-amoebic properties using Acanthamoeba castellanii of the T4 genotype. Conditioned media (CM) were prepared from bacteria isolated from WML. The CM were tested using amoebicidal, adhesion, encystation, excystation, cell cytotoxicity and amoeba-mediated host cell cytotoxicity assays in vitro. Amoebicidal assays revealed that CM exhibited anti-amoebic effects. CM inhibited both excystation and encystation in A. castellanii. CM inhibited amoebae binding to and cytotoxicity of host cells. In contrast, CM alone showed limited toxic effects against human cells in vitro. Mass spectrometry revealed several antimicrobials, anticancer, neurotransmitters, anti-depressant and other metabolites with biological functions. Overall, these findings imply that bacteria from unusual places, such as WML gut, produce molecules with anti-acanthamoebic capabilities. Full article

The emergence of drug-resistant bacterial strains that reduce the effectiveness of antimicrobial agents has become a major ongoing health concern in recent years. It is therefore necessary to find new antibacterials with broad-spectrum activity against both Gram-positive and Gram-negative bacteria, and/or to use nanotechnology to boost the potency of already available medications. In this research, we examined the antibacterial efficacy of sulfamethoxazole and ethacridine lactate loaded two-dimensional glucosamine functionalized graphene-based nanocarriers against a range of bacterial isolates. Graphene oxide was first functionalized with glucosamine, which as a carbohydrate moiety can render hydrophilic and biocompatible characters to the GO surface, and subsequently loaded with ethacridine lactate and sulfamethoxazole. The resulting nanoformulations had distinct, controllable physiochemical properties. By analyzing the formulation using Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (PXRD), a thermogravimetric analysis (TGA), zetasizer, and a morphological analysis using Scanning Electron Microscopy and Atomic Force Microscopy, researchers were able to confirm the synthesis of nanocarriers. Both nanoformulations were tested against Gram-negative bacteria, including Escherichia coli K1, Serratia marcescens, Pseudomonas aeruginosa, Salmonella enterica, as well as Gram-positive bacteria, including Bacillus cereus, Streptococcus pyogenes, and Streptococcus pneumoniae. Importantly, ethacridine lactate and its nanoformulations exhibited significant antibacterial properties against all bacteria tested in this study. When tested for minimum inhibitory concentration (MIC), the results were remarkable and revealed that ethacridine lactate presented MIC₉₀ at 9.7 µg/mL against S. enteric, and MIC₉₀ at 6.2 µg/mL against B. cereus. Notably, ethacridine lactate and its nanoformulations showed limited toxicity effects against human cells using lactate dehydrogenase assays. Overall, the results revealed that ethacridine lactate and its nanoformulations possess antibacterial activities against various Gram-negative and Gram-positive bacteria and that nanotechnology can be employed for the targeted delivery of effective drugs without harming the host tissue. Full article

Herein, we utilized several deep eutectic solvents (DES) that were based on hydrogen donors and hydrogen acceptors for their antibacterial application. These DES were tested for their bactericidal activities against Gram-positive (Streptococcus pyogenes, Bacillus cereus, Streptococcus pneumoniae, and methicillin-resistant Staphylococcus aureus) and Gram-negative (Escherichia coli K1, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Serratia marcescens) bacteria. Using lactate dehydrogenase assays, DES were evaluated for their cytopathic effects towards human cells. Results from antibacterial tests revealed that DES prepared from the combination of methyl-trioctylammonium chloride and glycerol (DES-4) and DES prepared form methyl-trioctylammonium chloride and fructose (DES-11) at a 2 µL dose showed broad-spectrum antibacterial behavior and had the highest bactericidal activity. Moreover, DES-4 showed 40% and 68% antibacterial activity against P. aeruginosa and E. coli K1, respectively. Similarly, DES-11 eliminated 65% and 61% E. coli K1 and P. aeruginosa, respectively. Among Gram-positive bacteria, DES-4 showed important antibacterial activity, inhibiting 75% of B. cereus and 51% of S. pneumoniae. Likewise, DES-11 depicted 70% B. cereus and 50% S. pneumoniae bactericidal effects. Finally, the DES showed limited cytotoxic properties against human cell lines with the exception of the DES prepared from Methyltrioctylammonium chloride and Citric acid (DES-10), which had 88% cytotoxic effects. These findings suggest that DES depict potent antibacterial efficacies and cause minimal damage to human cells. It can be concluded that the selected DES in this study could be utilized as valuable and novel antibacterial drugs against bacterial infections. In future work, the mechanisms for bactericides and the cytotoxicity effects of these DES will be investigated. Full article

Acanthamoeba castellanii is a ubiquitous free-living amoeba capable of instigating keratitis and granulomatous amoebic encephalitis in humans. Treatment remains limited and inconsistent. Accordingly, there is a pressing need for novel compounds. Nanotechnology has been gaining attention for enhancing drug delivery and reducing toxicity. Previous work has shown that various antibiotic classes displayed antiamoebic activity. Herein, we employed two antibiotics: ampicillin and ceftriaxone, conjugated with the nanocarrier zinc oxide and β-cyclodextrin, and tested them against A. castellanii via amoebicidal, amoebistatic, encystment, excystment, cytopathogenicity, and cytotoxicity assays at a concentration of 100 μg/mL. Notably, zinc oxide β-cyclodextrin ceftriaxone significantly inhibited A. castellanii growth and cytopathogenicity. Additionally, both zinc oxide β-cyclodextrin ceftriaxone and ceftriaxone markedly inhibited A. castellanii encystment. Furthermore, all the tested compounds displayed negligible cytotoxicity. However, minimal anti-excystment or amoebicidal effects were observed for the compounds. Accordingly, this novel nanoconjugation should be employed in further studies in hope of discovering novel anti-Acanthamoeba compounds. Full article

Microbial fuel cells (MFCs) are an environmentally friendly technology and a source of renewable energy. It is used to generate electrical energy from organic waste using bacteria, which is an effective technology in wastewater treatment. The anode and the cathode electrodes and proton exchange membranes (PEM) are important components affecting the performance and operation of MFC. Conventional materials used in the manufacture of electrodes and membranes are insufficient to improve the efficiency of MFC. The use of nanomaterials in the manufacture of the anode had a prominent effect in improving the performance in terms of increasing the surface area, increasing the transfer of electrons from the anode to the cathode, biocompatibility, and biofilm formation and improving the oxidation reactions of organic waste using bacteria. The use of nanomaterials in the manufacture of the cathode also showed the improvement of cathode reactions or oxygen reduction reactions (ORR). The PEM has a prominent role in separating the anode and the cathode in the MFC, transferring protons from the anode chamber to the cathode chamber while preventing the transfer of oxygen. Nanomaterials have been used in the manufacture of membrane components, which led to improving the chemical and physical properties of the membranes and increasing the transfer rates of protons, thus improving the performance and efficiency of MFC in generating electrical energy and improving wastewater treatment. Full article

Several technical factors contribute to the flow of cuttings from the wellbore to the surface of the well, some of which are fundamentally due to the speed and inclination of the drill pipe at different positions (concentric and eccentric), the efficacy of the drilling mud considers plastic viscosity (PV) and yield point (YP), the weight of the cuttings, and the deviation of the well. Moreover, these overlaying cutting beds breed destruction in the drilling operation, some of which cause stuck pipes, reducing the rate of rotation and penetration. This current study, while it addresses the apropos of artificial intelligence (AI) with symmetry, employs a three-dimensional computational fluid dynamic (CFD) simulation model to validate an effective synthetic-based mud-drilling and to investigate the potency of the muds’ flow behaviours for transporting cuttings. Furthermore, the study examines the ratio effects of YP/PV to attain the safe transport of cuttings based on the turbulence of solid-particle suspension from the drilling fluid and the cuttings, and its velocity–pressure influence in a vertical well under a concentric and eccentric position of the drilling pipe. The resulting CFD analysis explains that the YP/PV of SBM and OBM, which generated the required capacity to suspend the cuttings to the surface, are symmetric to the experimental results and hence, the position of the drill pipe at the concentric position in vertical wells required a lower rotational speed. A computational study of the synthetic-based mud and its potency of not damaging the wellbore under an eccentric drill pipe position can be further examined. Full article

Methylene blue (MB), an organic thiazine dye, has numerous industrial and medical applications. However, MB is a wastewater contaminant that is harmful to humans and aquatic life. Hence, its removal from water bodies is essential. In this work, five novel deep eutectic solvents (DESs) were synthesized using different precursors, screened, and studied for the extraction of methylene blue (MB) from aqueous solution using liquid–liquid extraction. The first, TOP-SA, was synthesized using trioctylphosphine (TOP) as a hydrogen bond acceptor (HBA) and 2-hydroxy benzoic acid as a hydrogen bond donor (HBD). Among these, TOP-SA had the highest MB removal efficiency. The effects of pH, contact time, initial MB concentration, volumetric ratio, temperature, and ionic strength were studied and optimized. A 99.3% removal was achieved in 5 min for a 200 mg dm⁻³ MB solution mixed in a 1:10 ratio with TOP-SA at 25.0 °C. The structural properties of TOP-SA and its interactions with MB were investigated using FTIR. TOP-SA’s toxicity was investigated using human cells in vitro. TOP-SA was found to be comparatively less toxic and is a more efficient MB remover than other literature reported ionic liquids (ILs). Full article

Naegleria fowleri and Balamuthia mandrillaris are opportunistic protists, responsible for fatal central nervous system infections such as primary amoebic meningoencephalitis (PAM) and granulomatous amoebic encephalitis (GAE) with mortality rates higher than 90%. Threatening a rise in cases is the increase in temperature due to global warming. No effective treatment is currently available. Herein, nanotechnology was used to conjugate Zinc oxide with Ampicillin, Ceftrixon, Naringin, Amphotericin B, and Quericitin, and the amoebicidal activity and host cell cytotoxicity of these resulting compounds were investigated. The compounds ZnO-CD-AMPi, ZnO-CD-CFT, ZnO-CD-Nar, ZnO-CD-AMB, and ZnO-CD-QT were found to reduce N. fowleri viability to 35.5%, 39.6%, 52.0%, 50.8%, 35.9%, and 69.9%, respectively, and B. mandrillaris viability to 40.9%, 48.2%, 51.6%, 43.8%, and 62.4%, respectively, when compared with their corresponding controls. Furthermore, the compounds reduced N. fowleri-mediated and B. mandrillaris-mediated host cell death significantly. Additionally, the compounds showed limited cytotoxicity against human cells; cell toxicity was 35.5%, 36.4%, 30.9%, 36.6%, and 35.6%, respectively, for the compounds ZnO-CD-AMPi, ZnO-CD-CFT, ZnO-CD-Nar, ZnO-CD-AMB, and ZnO-CD-QT. Furthermore, the minimum inhibitory concentrations to inhibit amoeba growth by 50% were determined for N. fowleri and B. mandrillaris. The MIC₅₀ for N. fowleri were determined to be 69.52 µg/mL, 82.05 µg/mL, 88.16 µg/mL, 95.61 µg/mL, and 85.69 µg/mL, respectively; the MIC₅₀ of the compounds for B. mandrillaris were determined to be 113.9 µg/mL, 102.3 µg/mL, 106.9 µg/mL, 146.4 µg/mL, and 129.6 µg/mL, respectively. Translational research to further develop therapies based on these compounds is urgently warranted, given the lack of effective therapies currently available against these devastating infections. Full article

Produced water contaminated with oil has adverse effects on human health and aquatic life. Providing an efficient method for the removal of oil from produced water is a challenging task. In this study, the effects of carbon chain length and the cation nature of ionic liquids (ILs) on the removal efficiency of oil from produced water were investigated. For this purpose, seven ILs containing the bis (trifluoromethylsulfonyl) imide (NTf₂) anion, and various cations such as imidazolium, pyridinium, phosphonium, and ammonium, were employed for the removal of oil from produced water via liquid–liquid extraction. The effects of process parameters such as the initial concentration of oil in produced water, contact time, pH, salinity, phase ratio, and temperature on the removal efficiency of oil were studied and optimized. 1-Decyl-3-methyl-imidazolium bis(trifluoromethylsulfonyl)imide ([C₁₀mim][NTf₂]) (IL4) was found to give the highest oil extraction efficiency of 92.8% under optimum conditions. The extraction efficiency was found to increase with increasing cation alkyl chain length from C₂ to C₁₀. The extraction efficiency of ILs based on cations follows the order imidazolium > ammonium > phosphonium > anpyridinium. Fourier Transform infrared spectroscopy (FTIR) was used to explore the ILs interaction with oil using [C₁₀mim][NTf₂] as a model. In addition, ¹H and ¹³C NMR spectra were recorded to obtain a better understanding of the molecular structure of IL and to investigate the peak shifts in H and C atoms. Moreover, the cell viability of the most efficient IL, [C₁₀mim][NTf₂], in human cells was investigated. It has been concluded that this IL exhibited minimal cytotoxic effects at lower concentrations against human cell lines and is effective for the extraction of oil from aqueous media. Full article

We examined the antiamoebic effect of several imidazothiazole derivatives on Acanthamoeba castellanii of the T4 genotype. Trypan blue exclusion assays and haemocytometer counting were used to determine the reduction in A. castellanii trophozoite proliferation, in response to treatment with these compounds. To determine the effects of these compounds on host cells, lactate dehydrogenase assay was performed using HeLa cell lines. Amoebicidal assays revealed that the tested compounds at concentrations of 50 µM significantly inhibited amoebae trophozoites compared to controls. Compounds 1m and 1zb showed the highest amoebicidal effects eradicating 70% and 67% of A. castellanii, respectively. The compounds blocked both the encystation and excystation process in A. castellanii. Compounds 1m and 1zb blocked 61% and 55%, respectively, of amoeba binding to human cells. Moreover, the compounds showed minimal cytotoxic effects against host cells and considerably reduced amoeba-mediated host cell death. Overall, our study revealed that compounds 1m and 1zb have excellent antiamoebic potential, and should be considered in the development of curative antiamoebic medications in future studies. Further work is critical to determine the translational value of these findings. Full article

The free-living amoeba Acanthamoeba castellanii is responsible for the central nervous infection granulomatous amoebic encephalitis and sight-threatening infection Acanthamoeba keratitis. Moreover, no effective treatment is currently present, and a combination drug therapy is used. In this study, twelve DNA minor groove binders (MGBs) were synthesized and tested for their antiamoebic activity via amoebicidal, encystation, excystation, and cytopathogenicity assays. It was found that the compounds MGB3, MGB6, MGB22, MGB24, and MGB16 significantly reduce amoeba viability to 76.20%, 59.45%, 66.5%, 39.32%, and 43.21%, respectively, in amoebicidal assays. Moreover, the compounds MGB6, MGB20, MGB22, MGB28, MGB30, MGB32, and MGB16 significantly inhibit Acanthamoeba cysts, leading to the development of only 46.3%, 39%, 30.3%, 29.6%, 27.8%, 41.5%, and 45.6% cysts. Additionally, the compounds MGB3, MGB4, MGB6, MGB22, MGB24, MGB28, MGB32, and MGB16 significantly reduce the re-emergence of cysts to trophozoites, with viable trophozoites being only 64.3%, 47.3%, 41.4%, 52.9%, 55.4%, 40.6%, 62.1%, and 51.7%. Moreover, the compounds MGB3, MGB4, and MGB6 exhibited the greatest reduction in amoeba-mediated host-cell death, with cell death reduced to 41.5%, 49.4%, and 49.5%. With the following determined, future in vivo studies can be carried out to understand the effect of the compounds on animal models such as mice. Full article

The unique structures and multifunctionalities of two-dimensional (2D) nanomaterials, such as graphene, have aroused increasing interest in the construction of novel scaffolds for biomedical applications due to their biocompatible and antimicrobial abilities. These two-dimensional materials possess certain common features, such as high surface areas, low cytotoxicities, and higher antimicrobial activities. Designing suitable nanocomposites could reasonably improve therapeutics and reduce their adverse effects, both medically and environmentally. In this study, we synthesized a biocompatible nanocomposite polyhydroxyalkanoate, chitosan, and tungsten disulfide (PHA/Ch-WS₂). The nanocomposite PHA/Ch-WS₂ was characterized by FESEM, elemental mapping, FTIR, and TGA. The objective of this work was to investigate the antimicrobial activity of PHA/Ch-WS₂ nanocomposites through the time–kill method against the multi-drug-resistant model organisms Escherichia coli (E. coli) K1 and methicillin-resistant Staphylococcus aureus (MRSA). Further, we aimed to evaluate the cytotoxicity of the PHA/Ch-WS₂ nanocomposite using HaCaT cell lines by using a lactate dehydrogenase (LDH) assay. The results demonstrated very significant bactericidal effects of the PHA/Ch-WS₂ nanocomposite, and thus, we hypothesize that the nanocomposite would feasibly suit biomedical and sanitizing applications without causing any adverse hazard to the environment. Full article