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Arsenic (As) is a semi-metal which causes health problems in human, and immune system has been documented as one of the main target of arsenic toxicity. Apoptosis has a crucial role in regulation of immune system, but it can also have an important role in As immune suppression. So, we decided to assess the comprehensive mechanism of As cytotoxic effect on lymphocytes isolated from human blood. We determine the direct effect of arsenic on human lymphocytes which have a key role in immune system functionality. To evaluate the mechanism of arsenic toxicity on human lymphocytes, we use accelerated cytotoxicity mechanisms screening (ACMS) technique. Lymphocytes were isolated from blood of healthy persons using Ficoll-paque PLUS standard method. Following treatment of human lymphocytes with 0.05-50 μM of arsenic for 12 h, cell viability was measured. For determination of mechanistic parameters, isolated human lymphocytes incubated with 1/2IC5012h (7.5 μM), IC5012h (15 μM) and 2IC5012h (30 μM) for 2, 4 and 6 h. The results of this study demonstrate arsenic-associated apoptosis in human lymphocytes is mainly through enhancement of intracellular calcium which causes oxidative stress and following adverse effect on lymphocytes organelles (like mitochondria and lysosome). Involvement of cellular proteolysis, activation of caspase-3, lipid peroxidation and stimulation of cytokines (IL2, INF-gamma and TNF-alpha) production were also associated with arsenic induced lymphocyte toxicity.

Lead (Pb) is one of the most important heavy metals that possess many applications in different kinds of industrial procedures and consumer products. The adverse effects of Pb on different parts of the immune system have been reported in various studies. Although it has been shown that high concentrations of Pb have low cytotoxicity on human lymphocytes, the effects of non-cytotoxic concentrations of Pb (detected in human blood) on cellular organelles and oxidative stress factors of human lymphocytes have yet to be determined. In this study, human lymphocytes were obtained from the blood of healthy male volunteers through the use of the Ficoll standard method. The intention of this paper was to determine the effects of non-cytotoxic concentrations of Pb on human lymphocytes using the accelerated cytotoxicity mechanism screening technique. For determination of cell viability, lymphocytes were treated with 0–1 mm Pb for 12 h. Subsequently, we assayed the effects of non-cytotoxic concentrations of Pb which are detected in human blood on human lymphocytes and investigated if Pb can affect oxidative stress and cellular organelles at these concentrations. So, in concentrations which have no cytotoxic effects, Pb is shown to induce oxidative stress in addition to inflicting damage on mitochondria and lysosomes in human blood lymphocytes.

Aims: Anxiety often coexists with migraine, and both conditions share a commonality in oxidative/nitrosative stress and mitochondrial dysfunction contributing to their pathogenesis. β‐Sitosterol, a plant sterol, has shown promise in mitigating oxidative/nitrosative stress, enhancing mitochondrial function, and exerting neuroprotective effects. In this study, we investigated the impact of β‐sitosterol on migraine‐associated anxiety and whether this effect was associated with alleviation of oxidative/nitrosative stress and improvement in mitochondrial function. Methods: Nitroglycerin was used to induce migraine in adult male Wistar rats. β‐Sitosterol treatment consisted of daily intraperitoneal injections (10 mg/kg) for 10 days following migraine induction. Anxiety levels were evaluated using open‐field test (OFT) and hole‐board test (HBT). Frontal cortex samples were analyzed for malondialdehyde (MDA), glutathione (GSH), reactive oxygen/nitrogen species, nitric oxide (NO) (markers of oxidative/nitrosative stress), and ATP (indicator of mitochondrial function). Results: Migraine induction led to impaired performance in both the OFT and the HBT. Concurrently, it elevated MDA, reactive oxygen/nitrogen species, and NO levels while diminishing GSH levels in the frontal cortex, signifying heightened oxidative/nitrosative stress. Moreover, ATP levels decreased, indicating mitochondrial dysfunction. Treatment with β‐sitosterol significantly restored performance in both behavioral assays and normalized the levels of MDA, GSH, reactive oxygen/nitrogen species, NO, and ATP. Conclusion: β‐Sitosterol exerted anxiolytic effects in migraine, which can be attributed to its ability to ameliorate oxidative/nitrosative stress and enhance mitochondrial function. [ABSTRACT FROM AUTHOR]

Aflatoxins, a group of toxic secondary metabolites produced by Aspergillus species, pose significant threats to human health due to their potent carcinogenic, mutagenic, and immunosuppressive properties. Chronic exposure to these contaminants, commonly found in staple foods such as maize and groundnuts, has been linked to an increased risk of liver cancer, growth impairment, and immune dysfunction. Several agents, such as calcium montmorillonite clay and Lactobacillus rhamnosus GG, have shown promise in reducing aflatoxin bioavailability and alleviating its toxic effects. Additionally, dietary supplements such as chlorophyllin, selenium, and N-acetylcysteine have demonstrated potential as adjuvants to counteract aflatoxin-induced oxidative stress and support liver function. In this treatise, some of the most discussed approaches to mitigating aflatoxin effects are explored in terms of their efficacy, safety, and potential mechanisms of action, which include direct aflatoxin binding, detoxification, cellular antioxidative, and hepatocellular protection properties. However, the effectiveness of these strategies can be influenced by various factors, such as dose, duration of exposure, and individual susceptibility. Therefore, further research is needed to optimize these interventions and develop new, targeted therapies for the prevention and treatment of aflatoxin-related diseases. This review aims to provide a comprehensive analysis of 18 pharmaceutical, nutraceutical, supplement, and probiotic strategies currently available for mitigating the deleterious effects of chronic aflatoxin exposure in humans and animal models. [ABSTRACT FROM AUTHOR]

Background: The therapeutic potential of Quercus infectoria (QI) gall, including its anti-inflammatory, antioxidant, and anticancer properties, is well-known. However, its impact on lung, gastric, and esophageal cancer cells remain unclear. This study aims to explore the effects of QI gall aqueous extract on cell viability, apoptosis, and gene expression in A549, BGC823, and KYSE-30 cell lines. Methods: A549, BGC823, and KYSE-30 cells were seeded in complete medium and incubated with different concentrations of QI gall extract for 24 hours. Cell viability was measured by an MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] assay. The induction of apoptosis was assessed through flow cytometric analysis after the adding FITC-conjugated Annexin V (Annexin VFITC) and propidium iodide (PI). The mRNA expression levels of CCND1, TP53, BCL2, and BAX genes were determined using Real-time Quantitative Polymerase Chain Reaction analysis. Results: The MTT assay demonstrated that treatment with QI gall extract significantly reduced the number of viable cells in the A549, BGC823, and KYSE-30 cell lines at IC50 concentrations of 440.1, 437.1, and 465.2 mg/ml, respectively. Additionally, compared to untreated cell population, the percentages of early apoptosis, late apoptosis, and necrosis in the A549, BGC823, and KYSE-30 cells significantly increased following treatment with QI gall extract (P< 0.05). Also, the treatment with QI gall extract influenced the expression of CCND1, TP53, BCL2, and BAX genes. Conclusions: The present findings indicated that the gall extract of QI can inhibit the growth of A549, BGC823, and KYSE-30 cells by inducing apoptosis, which may be mediated via mitochondria-dependent pathway. [ABSTRACT FROM AUTHOR]

Thrombosis is responsible for thousands of deaths in a myriad of countries particularly the developed ones. Venous thrombosis incidents such as deep vein thrombosis and thromboembolism are the inevitable results of the contemporary lifestyle. In this article, we have designed a new family of tehtrahydro pyrido pyrimidines inspired by structures of antiplatelet agents reported in the literature. Furthermore, 13 derivatives of our lead compound N'-benzylidene-7-(4-methoxyphenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-5-carbohydrazide have been synthesized. The molecular docking study was conducted on COX-1 enzyme (pdb: 2oye), Compounds 8b and 8d had the most calculated binding energy with ΔG values of −8.41 and −7.74 Kcal/mol, sequentially. The platelet aggregometry inhibition effects of the synthesized compounds have been measured on the voluntarily donated human platelets using BORN turbidimetry method. Furthermore, compound 8d showed the most potency with the IC50 value of 16.9 and 37.41 µM on the ADP and AA inducers, respectively. Generally, all the compounds with electron-withdrawing substituents showed plausible activity against the ADP-inducing platelet aggregation. Besides, electron-withdrawing compounds in para position showed an acceptable inhibitory effect on the AA platelet inducer. [ABSTRACT FROM AUTHOR]

Among the many types of central nervous system (CNS) disorders, seizures and epilepsy severely affect the quality of life and routine daily activity of the sufferers. We aimed to review research studies that investigated the effect of statins on the prevention and treatment of seizures and epilepsy. Both animal models and human studies were included in this review. This article starts with a brief introduction about seizure, its prevalence, treatment, and various animal models of seizures and epilepsy. Next, we discuss statin's mechanism of action, side effects, and effects on neurological disorders with a specific focus on seizures. Finally, the effects of different types of statins on seizures are compared. The present review gives a better understanding of the therapeutic effects of statins on neurological disorders in animal models and human studies. This permits researchers to set up study designs to resolve current ambiguities and contradictions on the beneficial effects of statins on neurological disorders. [ABSTRACT FROM AUTHOR]

In this work, a new series of 2-((1,5-diphenyl-1H-1,2,4-triazol-3-yl)thio)-N-phenylacetamide derivatives (9a–k) were synthesized and then evaluated for their antiepileptic activity against pentylenetetrazole (PTZ)-induced seizures in mice. The most potent synthesized compound was 3-chloro derivative, 9e, with an average latency time of 825 ± 281 seconds (mean ± SEM) and zero mortality. Moreover, compound 9e was more active than phenytoin (p < 0.1) but weaker than phenobarbital (p < 0.05) in the PTZ test. Further, a molecular docking study was performed to investigate the modes of interactions between the GABAA receptor and the synthesized compounds. Docking results indicate that all of the synthesized compounds place well into the active site of the GABAA receptor. In addition, compound 9e, with the highest anticonvulsant properties, demonstrates proper interactions and forms strong hydrogen bonds with key amino acid residues in the active site of the GABAA receptor. Additionally, it has exhibited higher binding energy in the docking study compared to phenobarbital and phenytoin as the standard antiepileptic agents. [ABSTRACT FROM AUTHOR]

Diabetes is becoming a major threat to the world. A novel series of hybrids of coumarin-dithiocarbamate were designed and synthesized, as potential alpha-glucosidase inhibitors targeting type 2 diabetes mellitus, in excellent yield and characterized by FTIR, 1H NMR, 13C NMR. The most potent compounds 6g and 6f exhibited significant alpha-glucosidase inhibitory activity with IC50 values of 85.0 ± 4.0 μM and 101.6 ± 4.7 μM respectively. Molecular docking studies of the designed compounds against alpha-glucosidase were also carried out to compare the binding affinities with IC50 values. The predicted binding modes are in good agreement with the IC50 values and showed that the accommodation of the moiety carbamothioyl-sulfanyl at the gate area, while the coumarin moiety is involved in hydrogen bond interaction with the key amino acid His279 in the bottom of the binding site. The kinetic mechanism investigated by Lineweaver-Burk plots exhibited that compound (6g) inhibit the alpha-glucosidase enzyme competitively to form an enzyme inhibitor complex. [ABSTRACT FROM AUTHOR]

Fed-batch cultivation is a well-known type of submerged fermentation that is frequently used in manufacture of recombinant proteins and various kinds of enzymes, owing to its ability to produce products with high concentrations and high efficiency. In fed-batch culture, several issues must be considered; most of them are also presented in batch culture. However, feed flow rate calculation only corresponds to fed-batch fermentation and its value has a significant impact on productivity, efficiency, final concentration of product, formation of by-products, and viscosity of the culture. From this background, the present review article is an effort to gather the information on feeding strategies for fed-batch cultivation of Escherichia coli, which is a well-known microorganism in the production of recombinant proteins and industrial enzymes, especially for therapeutic applications. Moreover, this review is an aid to comprehend and compare the fundamental concept of different feeding strategies and their advantages and drawbacks. [ABSTRACT FROM AUTHOR]

Curcumin has been previously shown to possess anti-myeloma effects. However, almost all of the previous reports are only based on observations from single viability methods in commonly used cell lines. We made an effort to examine the cytotoxic effects of different concentrations of curcumin on two less studied myeloma cell lines using two parallel techniques. Our findings provide further evidence for the use of curcumin in the treatment of myeloma. Moreover, the use of different methods and proper inhibitors are strongly recommended in future studies to determine the involvement of certain mediators. [ABSTRACT FROM AUTHOR]

Despite major progress in the field of skin tissue engineering and wound care products, reconstruction of skin defects still represents a significant challenge associated with impaired healing and wound infection. In the present study, a novel antibacterial 3 D spongy fibroin-based skin tissue engineering scaffold incorporated with vanillin-loaded keratin particles was fabricated through a freeze-drying process. The obtained scaffolds offered a well-connected porous structure with a pore size of higher than 100 nm, a high water uptake capacity (>700%) and slow in vitro degradation over 60 days, and drug release profile indicated a prolonged vanillin release up to 14 days from the scaffolds. Furthermore, anti-bacterial and in vitro cell experiments demonstrated a bactericidal activity by incorporating vanillin into the scaffolds, besides excellent cell attachment and cytocompatibility at lower vanillin concentrations (1, 5 and 10 mM, FKV1, FKV5 and FKV10, respectively); however, a significant cytotoxicity was observed at elevated vanillin concentration (20 mM, FKV20). Hence, these findings indicate that local delivery of incorporated vanillin within fibroin-based scaffolds presents promising potential for improving anti-bacterial biomaterials for skin tissue engineering. [ABSTRACT FROM AUTHOR]

Introduction: Advantages of using porous bio-nanocomposite scaffolds for maxillofacial fracture application and optimizing the internal surfaces of synthetic grafts using nanotechnology can accelerate the bone cell adhesion, mechanical properties and absorption rates. There are various studies that have been performed on porous scaffold, especially for the fractured and destroyed parts of the facial bones. The aim of this study was to investigate the experimental and numerical analysis of the porous scaffold, which undertakes static and dynamic loading conditions. Materials and Methods: The maxillofacial bone was modeled using the solid works software, and then it was inserted into the Abaqus software to achieve a more precise model that utilizes an isotropic linear substance. Thereafter, a proper micromechanical model reported evaluating the elastic modulus response on porosity value using various models. Additionally, an experimental analysis was conducted on a new calcium silicate (CS) bioceramic reinforced with magnetite nanoparticles (MNPs) using the space holder technique coated with the gentamicin drug loaded on gelatin polymer. The response of the bio-nanocomposites shape, which corresponds to different MNPs' weight fractions, was determined using the scanning electron microscopy (SEM) and X-ray diffraction (XRD) techniques. Results: The analysis of the scaffold implant showed that it is tightened at a torque of stiffness of 3mm in the implant, which leads to high mechanical tension. The results showed that the elastic modulus of the nanocomposites increased from 60±5 MPa to 145±5 MPa with increasing 15 wt% MNPs to the calcium silicate nanoparticles. Conclusion: The results indicated that addition of 15 wt% MNPs to the based bioceramics increased both compression strength and decrease the porosity value. [ABSTRACT FROM AUTHOR]

Background: In recent years, the method of constructing and evaluating the properties of polymer nanocomposite and bioactive ceramics in tissue engineering such as biocompatible scaffolds was studied by some researchers. Methods: In this study, the bio-nanocomposite scaffolds of Chitosan (CS)--Hydroxyapatite (HA)--Wllastonite (WS), incorporated with 0, 10, 20 and 30 wt% of zirconium were produced using a freeze-drying method. Also, the phase structure and morphology of scaffolds were investigated using X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM) and Energy Dispersive Spectroscopy (EDS). By analyzing the SEM images, the porosity of the scaffolds was observed in the normal bone area of the body. In the next step, bioactivity and biodegradability tests of the scaffolds were carried out. Due to the presence of hydrophilic components and the high-water absorption capacity of these materials, the bio-nanocomposite scaffolds were able to absorb water properly. After that, the mechanical properties of the scaffolds were studied. Results: The mechanical test results showed that the preparation of reinforced bionanocomposites containing 10 wt% of zirconium presented better properties compared to incorporated bio-nanocomposites with different loadings of zirconium. Conclusion: According to MTT assay results, the prepared scaffolds did not have cytotoxicity at different concentrations of scaffold extracts. Consequently, the investigated scaffold can be beneficial in bone tissue engineering applications because of its similarity to natural bone structure and its proper porosity. [ABSTRACT FROM AUTHOR]