Insights into the Effect of Chitosan and ß-Cyclodextrin Hybridization of Zeolite-A on Its Physicochemical and Cytotoxic Properties as a Bio-Carrier for 5-Fluorouracil: Equilibrium and Release Kinetics Studies.

Synthetic zeolite-A (ZA) was hybridized with two different biopolymers (chitosan and ß-cyclodextrin) producing biocompatible chitosan/zeolite-A (CS/ZA) and ß-cyclodextrin/zeolite-A (CD/ZA) biocomposites. The synthetic composites were assessed as bio-carriers of the 5-fluorouracil drug (5-Fu) with enhanced properties, highlighting the impact of the polymer type. The hybridization by the two biopolymers resulted in notable increases in the 5-Fu loading capacities, to 218.2 mg/g (CS/ZA) and 291.3 mg/g (CD/ZA), as compared to ZA (134.2 mg/g). The loading behaviors using ZA as well as CS/ZA and CD/ZA were illustrated based on the classic kinetics properties of pseudo-first-order kinetics (R2 > 0.95) and the traditional Langmuir isotherm (R2 = 0.99). CD/ZA shows a significantly higher active site density (102.7 mg/g) in comparison to CS/ZA (64 mg/g) and ZA (35.8 mg/g). The number of loaded 5-Fu per site of ZA, CS/ZA, and CD/ZA (>1) validates the vertical ordering of the loaded drug ions by multi-molecular processes. These processes are mainly physical mechanisms based on the determined Gaussian energy (<8 kJ/mol) and loading energy (<40 kJ/mol). Both the CS/ZA and CD/ZA 5-Fu release activities display continuous and controlled profiles up to 80 h, with CD/ZA exhibiting much faster release. According to the release kinetics studies, the release processes contain non-Fickian transport release properties, suggesting cooperative diffusion and erosion release mechanisms. The cytotoxicity of 5-Fu is also significantly enhanced by these carriers: 5-Fu/ZA (11.72% cell viability), 5-Fu/CS/ZA (5.43% cell viability), and 5-Fu/CD/ZA (1.83% cell viability).

Synthesis and Characterization of Methoxy-Exfoliated Montmorillonite Nanosheets as Potential Carriers of 5-Fluorouracil Drug with Enhanced Loading, Release, and Cytotoxicity Properties.

Natural bentonite clay (BE) underwent modification steps that involved the exfoliation of its layers into separated nanosheets (EXBE) and further functionalization of these sheets with methanol, forming methoxy-exfoliated bentonite (Mth/EXBE). The synthetically modified products were investigated as enhanced carriers of 5-fluorouracil as compared to raw bentonite. The modification process strongly induced loading properties that increased to 214.4 mg/g (EXBE) and 282.6 mg/g (Mth/EXBE) instead of 124.9 mg/g for bentonite. The loading behaviors were illustrated based on the kinetic (pseudo-first-order model), classic isotherm (Langmuir model), and advanced isotherm modeling (monolayer model of one energy). The Mth/EBE carrier displays significantly higher loading site density (95.9 mg/g) as compared to EXBE (66.2 mg/g) and BE (44.9 mg/g). The loading numbers of 5-Fu in each site of BE, EXBE, and Mth/EXBE (>1) reflect the vertical orientation of these loaded ions involving multi-molecular processes. The loading processes that occurred appeared to be controlled by complex physical and weak chemical mechanisms, considering both Gaussian energy (<8 KJ/mol) as well as loading energy (<40 KJ/mol). The releasing patterns of EXBE and Mth/EXBE exhibit prolonged and continuous properties up to 100 h, with Mth/EXBE displaying much faster behaviors. Based on the release kinetic modeling, the release reactions exhibit non-Fickian transport release properties, validating cooperative diffusion and erosion release mechanisms. The cytotoxicity of 5-Fu is also significantly enhanced by these carriers: 5-Fu/BE (8.6% cell viability), 5-Fu/EXBE (2.21% cell viability), and 5-Fu/Mth/EXBE (0.73% cell viability).

Insight into the Morphological Properties of Nano-Kaolinite (Nanoscrolls and Nanosheets) on Its Qualification as Delivery Structure of Oxaliplatin: Loading, Release, and Kinetic Studies.

Natural kaolinite underwent advanced morphological-modification processes that involved exfoliation of its layers into separated single nanosheets (KNs) and scrolled nanoparticles as nanotubes (KNTs). Synthetic nanostructures have been characterized as advanced and effective oxaliplatin-medication (OXAP) delivery systems. The morphological-transformation processes resulted in a remarkable enhancement in the loading capacity to 304.9 mg/g (KNs) and 473 mg/g (KNTs) instead of 29.6 mg/g for raw kaolinite. The loading reactions that occurred by KNs and KNTs displayed classic pseudo-first-order kinetics (R2 > 0.90) and conventional Langmuir isotherms (R2 = 0.99). KNTs exhibit a higher active site density (80.8 mg/g) in comparison to KNs (66.3 mg/g) and raw kaolinite (6.5 mg/g). Furthermore, compared to KNs and raw kaolinite, each site on the surface of KNTs may hold up to six molecules of OXAP (n = 5.8), in comparison with five molecules for KNs. This was accomplished by multi-molecular processes, including physical mechanisms considering both the Gaussian energy (<8 KJ/mol) and the loading energy (<40 KJ/mol). The release activity of OXAP from KNs and KNTs exhibits continuous and regulated profiles up to 100 h, either by KNs or KNTs, with substantially faster characteristics for KNTs. Based on the release kinetic investigations, the release processes have non-Fickian transport-release features, indicating cooperative-diffusion and erosion-release mechanisms. The synthesized structures have a significant cytotoxicity impact on HCT-116 cancer cell lines (KNs (71.4% cell viability and 143.6 g/mL IC-50); KNTs (11.3% cell viability and 114.3 g/mL IC-50). Additionally, these carriers dramatically increase OXAP's cytotoxicity (2.04% cell viability, 15.4 g/mL IC-50 (OXAP/KNs); 0.6% cell viability, 4.5 g/mL IC-50 (OXAP/KNTs)).

Multifarious roles of mTOR signaling in cognitive aging and cerebrovascular dysfunction of Alzheimer's disease.

Age-related cognitive failure is a main devastating incident affecting even healthy people. Alzheimer's disease (AD) is the utmost common form of dementia among the geriatric community. In the pathogenesis of AD, cerebrovascular dysfunction is revealed before the beginning of the cognitive decline. Mounting proof shows a precarious impact of cerebrovascular dysregulation in the development of AD pathology. Recent studies document that the mammalian target of rapamycin (mTOR) acts as a crucial effector of cerebrovascular dysregulation in AD. The mTOR contributes to brain vascular dysfunction and subsequence cerebral blood flow deficits as well as cognitive impairment. Furthermore, mTOR causes the blood-brain barrier (BBB) breakdown in AD models. Inhibition of mTOR hyperactivity protects the BBB integrity in AD. Furthermore, mTOR drives cognitive defect and cerebrovascular dysfunction, which are greatly prevalent in AD, but the central molecular mechanisms underlying these alterations are obscure. This review represents the crucial and current research findings regarding the role of mTOR signaling in cognitive aging and cerebrovascular dysfunction in the pathogenesis of AD.

Revisiting the Amyloid Cascade Hypothesis: From Anti-Aß Therapeutics to Auspicious New Ways for Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder related to age, characterized by the cerebral deposition of fibrils, which are made from the amyloid-ß (Aß), a peptide of 40-42 amino acids. The conversion of Aß into neurotoxic oligomeric, fibrillar, and protofibrillar assemblies is supposed to be the main pathological event in AD. After Aß accumulation, the clinical symptoms fall out predominantly due to the deficient brain clearance of the peptide. For several years, researchers have attempted to decline the Aß monomer, oligomer, and aggregate levels, as well as plaques, employing agents that facilitate the reduction of Aß and antagonize Aß aggregation, or raise Aß clearance from brain. Unluckily, broad clinical trials with mild to moderate AD participants have shown that these approaches were unsuccessful. Several clinical trials are running involving patients whose disease is at an early stage, but the preliminary outcomes are not clinically impressive. Many studies have been conducted against oligomers of Aß which are the utmost neurotoxic molecular species. Trials with monoclonal antibodies directed against Aß oligomers have exhibited exciting findings. Nevertheless, Aß oligomers maintain equivalent states in both monomeric and aggregation forms; so, previously administered drugs that precisely decrease Aß monomer or Aß plaques ought to have displayed valuable clinical benefits. In this article, Aß-based therapeutic strategies are discussed and several promising new ways to fight against AD are appraised.

Combination Drug Therapy for the Management of Alzheimer's Disease.

Alzheimer's disease (AD) is the leading cause of dementia worldwide. Even though the number of AD patients is rapidly growing, there is no effective treatment for this neurodegenerative disorder. At present, implementation of effective treatment approaches for AD is vital to meet clinical needs. In AD research, priorities concern the development of disease-modifying therapeutic agents to be used in the early phases of AD and the optimization of the symptomatic treatments predominantly dedicated to the more advanced AD stages. Until now, available therapeutic agents for AD treatment only provide symptomatic treatment. Since AD pathogenesis is multifactorial, use of a multimodal therapeutic intervention addressing several molecular targets of AD-related pathological processes seems to be the most practical approach to modify the course of AD progression. It has been demonstrated through numerous studies, that the clinical efficacy of combination therapy (CT) is higher than that of monotherapy. In case of AD, CT is more effective, mostly when started early, at slowing the rate of cognitive impairment. In this review, we have covered the major studies regarding CT to combat AD pathogenesis. Moreover, we have also highlighted the safety, tolerability, and efficacy of CT in the treatment of AD.

Cadmium-induced lung injury is associated with oxidative stress, apoptosis, and altered SIRT1 and Nrf2/HO-1 signaling; protective role of the melatonin agonist agomelatine.

Cadmium (Cd) is a hazardous heavy metal extensively employed in manufacturing polyvinyl chloride, batteries, and other industries. Acute lung injury has been directly connected to Cd exposure. Agomelatine (AGM), a melatonin analog, is a drug licensed for treating severe depression. This study evaluated the effect of AGM against Cd-induced lung injury in rats. AGM was administered in a dose of 25 mg/kg/day orally, while cadmium chloride (CdCl2) was injected intraperitoneally in a dose of 1.2 mg/kg to induce lung injury. Pre-treatment with AGM remarkably ameliorated Cd-induced lung histopathological abrasions. AGM decreased reactive oxygen species (ROS) production, lipid peroxidation, suppressed NDAPH oxidase, and boosted the antioxidants. AGM increased Nrf2, GCLC, HO-1, and TNXRD1 mRNA, as well as HO-1 activity and downregulated Keap1. AGM downregulated Bax and caspase-3 and upregulated Bcl-2, SIRT1, and FOXO3 expression levels in the lung. In conclusion, AGM has a protective effect against Cd-induced lung injury via its antioxidant and anti-apoptotic effects mediated via regulating Nrf2/HO-1 and SIRT1/FOXO3 signaling.

Correction: Characterization of chitosan- and ß-cyclodextrin-modified forms of magnesium-doped hydroxyapatites as enhanced carriers for levofloxacin: loading, release, and anti-inflammatory properties.

[This corrects the article DOI: 10.1039/D4RA02144D.].

Characterization of chitosan- and ß-cyclodextrin-modified forms of magnesium-doped hydroxyapatites as enhanced carriers for levofloxacin: loading, release, and anti-inflammatory properties.

An advanced form of magnesium-rich hydroxyapatite (Mg·HAP) was modified with two types of biopolymers, namely chitosan (CH/Mg·HAP) and ß-cyclodextrin (CD/Mg·HAP), producing two types of bio-composites. The synthesized materials were developed as enhanced carriers for levofloxacin to control its loading, release, and anti-inflammatory properties. The polymeric modification significantly improved the loading efficiency to 281.4 mg g-1 for CH/Mg·HAP and 332.4 mg g-1 for CD/Mg·HAP compared with 218.3 mg g-1 for Mg·HAP. The loading behaviors were determined using conventional kinetic and isotherm models and mathematical parameters of new equilibrium models (the monolayer model of one energy). The estimated density of effective loading sites (Nm (LVX) = 88.03 mg g-1 (Mg·HAP), 115.8 mg g-1 (CH/Mg·HAP), and 138.5 mg g-1 (CD/Mg·HAP)) illustrates the markedly higher loading performance of the modified forms of Mg·HAP. Moreover, the loading energies (<40 kJ mol-1) in conjunction with the capacity of each loading site (n > 1) and Gaussian energies (<8 kJ mol-1) signify the physical trapping of LVX molecules in vertical orientation. The addressed materials validate prolonged and continuous release behaviors. These behaviors accelerated after the modification procedures, as the complete release was identified after 160 h (CH/Mg·HAP) and 200 h (CD/Mg·HAP). The releasing behaviors are regulated by both diffusion and erosion mechanisms, according to the kinetic investigations and diffusion exponent analysis (>0.45). The entrapping of LVX into Mg·HAP induces its anti-inflammatory properties against the generation of cytokines (IL-6 and IL-8) in human bronchial epithelia cells (NL20), and this effect displays further enhancement after the integration of chitosan and ß-cyclodextrin.

Cadmium cardiotoxicity is associated with oxidative stress and upregulated TLR-4/NF-kB pathway in rats; protective role of agomelatine.

Cardiotoxicity is one of the hazardous effects of the exposure to the heavy metal cadmium (Cd). Inflammation and oxidative injury are implicated in the cardiotoxic mechanism of Cd. The melatonin receptor agonist agomelatine (AGM) showed promising effects against oxidative and inflammatory responses. This study evaluated the effect of AGM on Cd-induced cardiotoxicity in rats, pointing to its modulatory effect on TLR-4/NF-kB pathway and HSP70. Rats received AGM for 14 days and a single dose of Cd on day 7 and blood and heart samples were collected for analyses. Cd increased serum CK-MB, AST and LDH and caused cardiac tissue injury. Cardiac malondialdehyde (MDA), nitric oxide (NO) and MPO were elevated and GSH, SOD and GST decreased in Cd-administered rats. AGM ameliorated serum CK-MB, AST and LDH and cardiac MDA, NO and MPO, prevented tissue injury and enhanced antioxidants. AGM downregulated serum CRP and cardiac TLR-4, NF-kB, iNOS, IL-6, TNF-α and COX-2 in Cd-administered rats. HSP70 was upregulated in the heart of Cd-challenged rats treated with AGM. In silico findings revealed the binding affinity of AGM with TLR-4 and NF-kB. In conclusion, AGM protected against Cd cardiotoxicity by preventing myocardial injury and oxidative stress and modulating HSP70 and TLR-4/NF-kB pathway.

Silver Nanoparticles of Artemisia sieberi Extracts: Chemical Composition and Antimicrobial Activities.

BACKGROUND: Artemisia sieberi (mugwort) is a member of the daisy family Asteraceae and is widely propagated in Saudi Arabia. A. sieberi has historical medical importance in traditional societies. The current study aimed to assess the antibacterial and antifungal characteristics of the aqueous and ethanolic extracts of A. sieberi. In addition, the study investigated the effect of silver nanoparticles (AgNPs) synthesized from the A. sieberi extract. METHODS: The ethanolic and aqueous extracts and AgNPs were prepared from the shoots of A. sieberi. The characteristics of AgNPs were assessed by UV-visible spectroscopy, transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS). The antibacterial experiments were performed against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa. The fungal species used were Candida parapsilosis, Candida krusei, Candida famata, Candida rhodotorula, and Candida albicans. The antibacterial and antifungal characteristics were evaluated by measuring the diameter of growing organisms in Petri dishes treated with different concentrations of either extracts or AgNPs compared to the untreated controls. Furthermore, TEM imaging was used to investigate any ultrastructure changes in the microbes treated with crude extracts and AgNO3. RESULTS: The ethanolic and aqueous extracts significantly decreased the growth of E. coli, S. aureus, and B. subtilis (p < 0.001), while P. aeruginosa was not affected. Unlike crude extracts, AgNPs had more substantial antibacterial effects against all species. In addition, the mycelial growth of C. famata was reduced by the treatment of both extracts. C. krusei mycelial growth was decreased by the aqueous extract, while the growth of C. parapsilosis was affected by the ethanolic extract and AgNPs (p < 0.001). None of the treatments affected the growth of C. albicans or C. rhodotorula. TEM analysis showed cellular ultrastructure changes in the treated S. aureus and C. famata compared to the control. CONCLUSION: The biosynthesized AgNPs and extracts of A. sieberi have a potential antimicrobial characteristic against pathogenic bacterial and fungal strains and nullified resistance behavior.

Synthesis and Characterization of ß-Cyclodextrin-Hybridized Exfoliated Kaolinite Single Nanosheets as Potential Carriers of Oxaliplatin with Enhanced Loading, Release, and Cytotoxic Properties.

Natural kaolinite was subjected to a successful exfoliation process into separated kaolinite nanosheets (KNs), followed by hybridization with ß-cyclodextrin biopolymer (ß-CD), forming an advanced bio-nanocomposite (ß-CD/KNs). The synthetic products were evaluated as enhanced delivery structures for oxaliplatin chemotherapy (OXAPN). The hybridization of KNs with ß-CD polymer notably enhanced the loading capacity to 355.3 mg/g (ß-CD/KNs) as compared to 304.9 mg/g for KNs. The loading of OXAPN into both KNs and ß-CD/KNs displayed traditional pseudo-first-order kinetics (R2 > 0.85) and a conventional Langmuir isotherm (R2 = 0.99). The synthetic ß-CD/KNs validates a greater occupied effective site density (98.7 mg/g) than KNs (66.3 mg/g). Furthermore, the values of the n steric parameter (4.7 (KNs) and 3.6 (ß-CD/KNs)) reveal the vertical orientation of the loaded molecules and the loading of them by multi-molecular mechanisms. These mechanisms are mainly physical processes based on the obtained Gaussian energy (<8 KJ/mol) and loading energy (<40 KJ/mol). The release profiles of both KNs and ß-CD/KNs extend for about 120 h, with remarkably faster rates for ß-CD/KNs. According to the release kinetic findings, the release of OXAPN displays non-Fickian transport behavior involving the cooperation of diffusion and erosion mechanisms. The KNs and ß-CD/KNs as free particles showed considerable cytotoxicity and anticancer properties against HCT-116 cancer cell lines (71.4% cell viability (KNs) and 58.83% cell viability (ß-CD/KNs)). Additionally, both KNs and ß-CD/KNs significantly enhanced the OXAPN's cytotoxicity (2.04% cell viability (OXAPN/KNs) and 0.86% cell viability (OXAPN/ß-CD/KNs).

Characterization of Chitosan-Hybridized Diatomite as Potential Delivery Systems of Oxaliplatin and 5-Fluorouracil Drugs: Equilibrium and Release Kinetics.

The current work involves the modification of diatomite's biosiliceous frustules employing chitosan polymer chains (CS/Di) to serve as low-cost, biocompatible, multifunctional, and enhanced pharmaceutical delivery systems for 5-fluorouracil (5-Fu) together with oxaliplatin (OXPL). The CS/Di carrier displayed strong loading characteristics, notably at saturation (249.17 mg/g (OXPL) and 267.6 mg/g (5-Fu)), demonstrating a substantial 5-Fu affinity. The loading of the two types of medications onto CS/Di was conducted based on the kinetic behaviors of the conventional pseudo-first-order theory (R2 > 0.90). However, while the loading of OXPL follows the isotherm assumptions of the classic Langmuir model (R2 = 0.99), the loading of 5-Fu displays Fruendlich isotherm properties. Therefore, the 5-Fu loading displayed physical, heterogeneous, and multilayer loading properties, whereas the loading of OXPL occurred in homogeneous and monolayer form. The densities of occupied active sites of CS/Di were 37.19 and 32.8 mg/g for the sequestrations of OXPL and 5-Fu, respectively. Furthermore, by means of multimolecular processes, each loading site of CS/Di can bind up to 8 molecules of OXPL and 9 molecules of 5-Fu in a vertical orientation. This observation explains the higher loading capacities of 5-Fu in comparison to OXPL. The loading energies, which exhibit values <40 kJ/mol, provide confirmation of the dominant and significant consequences of physical processes as the regulating mechanisms. The release patterns of OXPL and 5-Fu demonstrate prolonged features over a duration of up to 120 h. The release kinetic simulation and diffusion exponents which are more than 0.45 provide evidence of the release of OXP and 5-Fu via non-Fickian transportation characteristics and the erosion/diffusion mechanism. The CS/Di carrier exhibited a substantial enhancement in the cytotoxicity of OXPL and 5-Fu against HCT-116 carcinoma cell lines, resulting in a reduction in cell viability by 4.61 and 2.26% respectively.

Multi-Target Drug Candidates for Multifactorial Alzheimer's Disease: AChE and NMDAR as Molecular Targets.

Alzheimer's disease (AD) is one of the most common forms of dementia among elder people, which is a progressive neurodegenerative disease that results from a chronic loss of cognitive activities. It has been observed that AD is multifactorial, hence diverse pharmacological targets that could be followed for the treatment of AD. The Food and Drug Administration has approved two types of medications for AD treatment such as cholinesterase inhibitors (ChEIs) and N-methyl-D-aspartic acid receptor (NMDAR) antagonists. Rivastigmine, donepezil, and galantamine are the ChEIs that have been approved to treat AD. On the other hand, memantine is the only non-competitive NMDAR antagonist approved in AD treatment. As compared with placebo, it has been revealed through clinical studies that many single-target therapies are unsuccessful to treat multifactorial Alzheimer's symptoms or disease progression. Therefore, due to the complex nature of AD pathophysiology, diverse pharmacological targets can be hunted. In this article, based on the entwined link of acetylcholinesterase (AChE) and NMDAR, we represent several multifunctional compounds in the rational design of new potential AD medications. This review focus on the significance of privileged scaffolds in the generation of the multi-target lead compound for treating AD, investigating the idea and challenges of multi-target drug design. Furthermore, the most auspicious elementary units for designing as well as synthesizing hybrid drugs are demonstrated as pharmacological probes in the rational design of new potential AD therapeutics.

Quercetin prevents myocardial infarction adverse remodeling in rats by attenuating TGF-ß1/Smad3 signaling: Different mechanisms of action.

This study investigated the anti-remodeling and anti-fibrotic and effect of quercetin (QUR) in the remote non-infarcted of rats after myocardial infarction (MI). Rats were divided as control, control + QUR, MI, and MI + QUR. MI was introduced to the rats by ligating the eft anterior descending (LAD) coronary artery. All treatments were given for 30 days, daily. QUR persevered the LV hemodynamic parameters and prevented remote myocardium damage and fibrosis. Also, QUR supressed the generation of ROS, increased the nuclear levels of Nrf2, and enhanced SOD and GSH levels in the LVs of the control and MI model rats. It also reduced angiotensin II, nuclear level/activity of the nuclear factor NF-κß p65, and protein expression of TGF-ß1, α-SMA, and total/phospho-smad3 in the LVs of both groups. Concomitantly, QUR upregulated LV smad7 and BMP7. In conclusion, QUR prevents MI-induced LV remodeling by antioxidant, anti-inflammatory, and anti-fibroticα effects mediated by ROS scavenging, suppressing NF-κß, and stimulating Nrf-2, Smad7, and BMP7.

Potential protective effects of Spirulina platensis on liver, kidney, and brain acrylamide toxicity in rats.

Acrylamide (AA) is a hazardous chemical that is widely used in industrial practices. Spirulina platensis (SP) is a blue green alga that is rich in bioactive compounds with many medicinal benefits. The aim of the present study was to evaluate the ameliorative effect of SP against AA toxicity in rats. Animals were divided into six groups: Group (1) was normal rats, groups (2) and (3) received SP at 500 and 1000 mg/kg BW orally respectively for 21 days, group (4) was administered 20 mg/kg BW AA daily for 14 days, while groups (5) and (6) were given orally SP at the same doses of groups (2) and (3), then AA at similar dose of group (4). Rats that received AA alone displayed markedly increased serum levels of liver enzymes (ALT, AST, and ALP), kidney function parameters (urea and creatinine), DNA damage marker (8-OHdG), and proinflammatory cytokines (IL-1ß, IL-6, and TNF-α), compared to control rats. Furthermore, tissue analysis revealed marked increases in hepatic, renal, and brain MDA and NO, as well as marked reductions in the antioxidant biomarkers (GSH, GSH-Px, SOD, and CAT) in acrylamide-intoxicated rats. Spirulina ameliorated the alterations in serum biochemical parameters and reduced MDA and NO, as well as improved antioxidant biomarkers in AA-intoxicated rats in a dose-dependent manner. Our results show that SP has a powerful protective effect on serum biochemistry and liver, kidney, and brain antioxidant machinery in AA-intoxicated rats.

Genetic Diversity of SARS-CoV2 and Environmental Settings: Possible Association with Neurological Disorders.

The new coronavirus (CoV), called novel coronavirus disease 2019 (COVID-19), belongs to the Coronaviridae family which was originated from the sea market in Wuhan city in China, at the end of the year 2019. COVID-19 and severe acute respiratory syndrome (SARS) are belonging to the same family (Coronaviridae). The current outbreak of COVID-19 creates public concern and threats all over the world and now it spreads out to more than 250 countries and territories. The researchers and scientists from all over the world are trying to find out the therapeutic strategies to abate the morbidity and mortality rate of the COVID-19 pandemic. The replication, spreading, and severity of SARS-CoV2 depend on environmental settings. Noteworthy, meteorological parameters are considered as crucial factors that affect respiratory infectious disorders, although the controversial effect of the meteorological parameter is exposed against COVID-19. Besides, COVID-19 accelerates the pathogenesis of the neurological disorders. However, the pathogenic mechanisms between COVID-19 and neurological disorders are still unclear. Hence, this review is focused on the genomics and ecology of SARS-CoV2 and elucidated the effects of climatic factors on the progression of COVID-19. This review also critically finds out the vulnerability between COVID-19 and neurological disorders based on the latest research data.

Molecular Mechanisms of Metal Toxicity in the Pathogenesis of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia, which is progressively affecting elderly people. The dyshomeostasis of biometals and accumulation of toxic metals are usually observed in numerous neurodegenerative diseases including AD. In the central nervous system, metal imbalance-caused neurotoxic activities are usually linked with decreased enzymatic activities, increased aggregation of proteins, and oxidative stress, where a series of processes can result in neurodegeneration and cell death. Even though the relations between neurodegenerative diseases and biometal imbalance are still elusive, there is a growing interest in a group of major endogenous proteins that are associated with the transports of metals. Aberrant expression of these endogenous proteins is associated with the biometal imbalance and AD pathogenesis. Indeed, heavy metals are extremely toxic to the nervous system. Various studies have demonstrated that the toxic effects of heavy metals can result in amyloid beta (Aß) aggregation, neurofibrillary tangles, and even loss of neurons. In this article, we have focused on the molecular processes through which exposure to biometals and toxic metals can play roles in AD pathogenesis.

Correction to: "Synthesis of Chitosan/Diatomite Composite as an Advanced Delivery System for Ibuprofen Drug; Equilibrium Studies and the Release Profile".

[This corrects the article DOI: 10.1021/acsomega.1c01514.].

Enhancing the Catalytic Performance of NiO during the Transesterification of Waste Cooking Oil Using a Diatomite Carrier and an Integrated Ni0 Metal: Response Surface Studies.

Two types of NiO-based composites (NiO@diatomite and Ni/NiO@diatomite) were synthesized as modified products of enhanced catalytic performances during the transesterification reactions of waste cooking oil. The influence of the diatomite substrate and the integration of metallic Ni0 in inducing the catalytic activity were evaluated in a series of transesterification reactions. The experimental conditions were adjusted according to the response surface methodology and the central composite statistical design. Experimentally, the diatomite substrate and the Ni0 metal induced the efficiency of the reaction to achieve a yield of 73.4% (NiO@diatomite) and 91% (Ni/NiO@diatomite), respectively, as compared to 66% for the pure phase (NiO). This was obtained under experimental conditions of 80 °C temperature, 100 min time, 12:1 methanol/oil molar ratio, and 3.75 wt % loading. The theoretical optimization functions of the designs suggested enhancement to the experimental conditions to achieve a yield of 76.3% by NiO@diatomite and 93.2% by Ni/NiO@diatomite. This reflected the role of the diatomite substrate in enhancing the surface area, the adsorption of fatty acids, and the exposure of the catalytic sites in addition to the effect of the Ni0 metal in enhancing the catalytic reactivity of the final product. Finally, the biodiesel produced over Ni/NiO@diatomite as the best product was of acceptable properties according to the international standards.