Farnesol attenuates cadmium-induced kidney injury by mitigating oxidative stress, inflammation and necroptosis and upregulating cytoglobin and PPARγ in rats

Heavy metals are environmental pollutants that can harm animals and humans even at low concentrations. Cadmium (Cd) is known for its serious health effects on different organs and its toxicity is associated with oxidative stress (OS) and inflammation. Farnesol (FAR), a sesquiterpene alcohol found in many vegetables and fruits, possesses promising anti-inflammatory and antioxidant activities. This study evaluated the effect of FAR on Cd-induced kidney injury, pinpointing its effect of the redox status, inflammation, fibrosis and necroptosis. Rats in this study received FAR for 14 days and Cd on day 7. Elevated serum creatinine, urea and uric acid, and several kidney histopathological alterations were observed in Cd-administered rats. Cd increased MDA, decreased antioxidants, downregulated PPARγ and upregulated NF-κB p65, IL-6, TNF-α, and IL-1β. Necroptosis mediators (RIP1, RIP3, MLKL, and caspase-8) and α-SMA were upregulated, and collagen deposition was increased in Cd-administered rats. FAR ameliorated kidney injury markers and tissue damage, attenuated OS, suppressed NF-κB and inflammatory mediators, and enhanced antioxidants. In addition, FAR suppressed RIP1, RIP3, MLKL, caspase-8, and α-SMA, and enhanced kidney cytoglobin and PPARγ. In conclusion, FAR protects against Cd nephrotoxicity by suppressing OS, inflammatory response and necroptosis, effects associated with enhanced antioxidants, cytoglobin, and PPARγ

Propagation of Plane Waves in Generalized Piezo-thermoelastic Medium: Comparison Of Different Theories

ABSTRACT: In this paper, a general solution for the propagation of plane waves in generalized piezo-thermoelastic medium for two-dimensional problem under the different thermoelastic theories is investigated. We have included Coupled theory (CT), Lord-Schulman (L-S) and Green-Lindsay (G-L) theories. The normal mode analysis is used to obtain the exact expressions for the considered variables. The results of the physical quantities have been illustrated graphically by comparison between (CT), (L-S) and (G-L) theories. KEYWORDS: Piezo-thermoelastic, Relaxation time, Normal mode analysis, Generalized thermoelasticity. I INTRODUCTION Piezoelectric is considered one of the basic properties of crystals, ceramics, polymers, liquid crystals and some biological tissues (e.g. bone and tendon). Recent interest in the piezoelectric materials stems from their potential applications in intelligent structural systems, and piezoelectric is currently enjoying a greatest resurgence in both fundamental research and technical applications. The theory of thermo-piezoelectric was first proposed by Mindlin Thermoelasticity theories that predict a finite speed for the propagation of thermal signals have aroused much interest in the last three decades. These theories are known as generalized thermoelasticity theories. The first generalization of the thermoelasticity theory is due to Lord and Shulman [8] who introduced the theory of generalized thermoelasticity with one relaxation time through postulating a new law of heat conduction to replace the classical Fourier' law. This law contains the heat flux vector as well as its time derivative. It contains also a new constant that acts as a relaxation time. The heat equation of this theory is of the wave-type which ensuring finite speeds of propagation of heat and elastic waves. The remaining, governing equations for this theory, namely, the equations of motion and the constitutive relations remain the same as those for the coupled and the uncoupled theories. This theory was extended by Dhaliwal and Sherief [9] to general anisotropic media in the presence of heat sources. Othman [10] studied the Lord

Bioactive injectable mucoadhesive thermosensitive natural polymeric hydrogels for oral bone and periodontal regeneration

Periodontitis is an inflammation-related condition, caused by an infectious microbiome and host defense that causes damage to periodontium. The natural processes of the mouth, like saliva production and eating, significantly diminish therapeutic medication residency in the region of periodontal disease. Furthermore, the complexity and diversity of pathological mechanisms make successful periodontitis treatment challenging. As a result, developing enhanced local drug delivery technologies and logical therapy procedures provides the foundation for effective periodontitis treatment. Being biocompatible, biodegradable, and easily administered to the periodontal tissues, hydrogels have sparked substantial an intense curiosity in the discipline of periodontal therapy. The primary objective of hydrogel research has changed in recent years to intelligent thermosensitive hydrogels, that involve local adjustable sol-gel transformations and regulate medication release in reaction to temperature, we present a thorough introduction to the creation and efficient construction of new intelligent thermosensitive hydrogels for periodontal regeneration. We also address cutting-edge smart hydrogel treatment options based on periodontitis pathophysiology. Furthermore, the problems and prospective study objectives are reviewed, with a focus on establishing effective hydrogel delivery methods and prospective clinical applications

Comparative studies of free and immobilized phytase, produced by Penicillium purpurogenu GE1, using grafted alginate/carrageenan beads

Aim: The aim of the study was to immobilize the phytase enzyme produced by Penicillium purpurogenu GE1 on grafted alginate/carrageenan beads and study the properties of the immobilized enzyme in comparison with free ones. Materials and methods: The immobilization conditions were first optimized and then the optimum conditions of temperature and pH for the maximum activity of the immobilized and free enzyme were studied and compared. The stabilities of both immobilized and free phytase at moderate and low temperatures of 50 and 4°C, as well as their stability at the acidic pH of 4, were also studied. Finally, the activity of the immobilized enzyme was monitored over 20 successive repeated batches. Results: The maximum loading capacity was obtained after 20 h at the enzyme/acetate buffer dilution ratio of 1 : 2. The optimum temperature and pH of the immobilized enzyme, as compared with free state, were found to have shifted from 37 to 45°C and from pH 5.5 to 4, respectively. Moreover, the results also proved that when phytase in both immobilized and free states was subjected to an acidic pH of 4 for 45 min, or to a moderately high temperature of 50°C for 60 min, the activity of the former remained stable, whereas that of the latter showed substantial losses. In contrast, at the refrigerator shelf temperature of 4°C, dry and wet immobilized forms retained 100% activity for 12 weeks, whereas that of the free enzyme was completely lost within a shorter period of 4 weeks. Furthermore, the activity of the phytase enzyme immobilized on gel beads was maintained at the 100% level for more than 12 repeated batch utilizations of the beads. Conclusion: The results revealed that the physiological parameters of the immobilized enzyme were greatly improved compared with the free state. Further, the activity of the phytase enzyme immobilized on gel beads was maintained at the 100% level for more than 12 repeated batch cultivations of the beads

A Novel Role of Galectin-3 and Thyroglobulin in Prognosis and Differentiation of Different Stages of Thyroid Cancer and Elucidation of the Potential Contribution of Bcl-2, IL-8 and TNF-α

Thyroid cancer is among the most prevalent cancers with different types and stages. New markers are required for the prognosis and diagnosis of the disease. The present study aimed to detect the role of new markers, including galectin-3 (Gal-3) and thyroglobulin (TG), in the prognosis and staging of thyroid cancer. The study also investigated the potential apoptotic and inflammatory mechanisms involved in thyroid cancer through the determination of B-cell lymphoma 2 (Bcl-2), interleukin-8 (IL-8) and tumor necrosis factor α (TNFα) during the different stages of the cancer using a series of molecular methods. Histopathological and immunohistochemical examinations were also performed. A total of 300 subjects were classified into: 100 normal healthy subjects matched in age and sex, 100 patients with thyroid carcinoma stage I (T1N0M0) and 100 patients with thyroid carcinoma stage 2 (T2N1M1). Interestingly, the present study revealed a significant increase in the levels of TG and Gal-3 in thyroid cancer patients compared to the control group. Furthermore, the levels of Bcl-2, IL-8 and TNF-α significantly increased in the patient serum. The histopathological examination and immunohistochemical observations confirmed the molecular and hematological findings. Collectively, the present study concluded that serum TG and Gal-3 could be useful markers in the prognosis and staging of patients with thyroid cancer. Furthermore, the determination of Bax, Bcl-2, IL-8 and TNF-α levels constitute a major important marker for investigation of the mechanisms of apoptosis and inflammation in thyroid cancer. To our knowledge, this is the first study that used both galectin-3 and TG as tumor markers in the prognosis and differentiation between the different stages of cancer

Ameliorative Effect of Dabigatran on CFA-Induced Rheumatoid Arthritis via Modulating Kallikrein-Kinin System in Rats

Rheumatoid arthritis is an autoimmune disease that affects joints, leading to swelling, inflammation, and dysfunction in the joints. Recently, research efforts have been focused on finding novel curative approaches for rheumatoid arthritis, as current therapies are associated with adverse effects. Here, we examined the effectiveness of dabigatran, the antithrombotic agent, in treating complete Freund’s adjuvant (CFA)-induced arthritis in rats. Subcutaneous injection of a single 0.3 mL dosage of CFA into the rat’s hind leg planter surface resulted in articular surface deformities, reduced cartilage thickness, loss of intercellular matrix, and inflammatory cell infiltration. There were also increased levels of the Anti-cyclic citrullinated peptide antibody (ACPA), oxidative stress, and tissue Receptor activator of nuclear factor–kappa B ligand (RANKL). Proteins of the kallikrein-kinin system (KKS) were also elevated. The inhibitory effects of dabigatran on thrombin led to a subsequent inhibition of KKS and reduced Toll-like receptor 4 (TLR4) expression. These effects also decreased RANKL levels and showed anti-inflammatory and antioxidant effects. Therefore, dabigatran could be a novel therapeutic strategy for arthritis

A First Metabolite Analysis of Norfolk Island Pine Resin and Its Hepatoprotective Potential to Alleviate Methotrexate (MTX)-Induced Hepatic Injury

Drug-induced liver injury (DILI) represents a significant clinical challenge characterized by hepatic dysfunction following exposure to diverse medications. Methotrexate (MTX) is a cornerstone in treating various cancers and autoimmune disorders. However, the clinical utility of MTX is overshadowed by its ability to induce hepatotoxicity. The current study aims to elucidate the hepatoprotective effect of the alcoholic extract of Egyptian Araucaria heterophylla resin (AHR) on MTX-induced liver injury in rats. AHR (100 and 200 mg/kg) significantly decreased hepatic markers (AST, ALT, and ALP), accompanied by an elevation in the antioxidant’s markers (SOD, HO-1, and NQO1). AHR extract also significantly inhibited the TGF-β/NF-κB signaling pathway as well as the downstream cascade (IL-6, JAK, STAT-3, and cyclin D). The extract significantly reduced the expression of VEGF and p38 with an elevation in the BCL2 levels, in addition to a significant decrease in the IL-1β and TNF-α levels, with a prominent effect at a high dose (200 mg/kg). Using LC-HRMS/MS analysis, a total of 43 metabolites were tentatively identified, and diterpenes were the major class. This study presents AHR as a promising hepatoprotective agent through inhibition of the TGF-β/NF-κB and JAK/STAT3 pathways, besides its antioxidant and anti-inflammatory effects

Nephroprotective effects of Acacia senegal against aflatoxicosis via targeting inflammatory and apoptotic signaling pathways

Aflatoxin B1 (AFB1) is a common environmental pollutant that poses a major hazard to both humans and animals. Acacia senegal (Gum) is well-known for having antioxidant and anti-inflammatory bioactive compounds. Our study aimed to scout the nephroprotective effects of Acacia gum (Gum) against AFB1-induced renal damage. Four groups of rats were designed: Control, Gum (7.5 mg/kg), AFB1 (200 µg/kg b.w) and AFB1-Gum, rats were co-treated with both Gum and AFB1. Gas chromatography-mass spectrometry (GC/MS) analysis was done to determine the phytochemical constituents in Gum. AFB1 triggered profound alterations in kidney function parameters (urea, creatinine, uric acid, and alkaline phosphatase) and renal histological architecture. Additionally, AFB1 exposure evoked up-regulation of mRNA expression levels of inflammatory cytokines, including interleukin-6 (IL-6), tumor necrosis factor α (TNFα), inducible nitric oxide synthase (iNOS), and nuclear factor kB p65 (NF-κB/P65) in renal tissue. The oxidative distress and apoptotic cascade are also instigated by AFB1 intoxication as depicted in down-regulated protein expression of the nuclear factor erythroid 2–related factor 2 (Nrf2) and superoxide dismutase type 1 (SOD1) along with upregulation of cytochrome c (Cyto c), and cleaved Caspase3 (Casp3–17 and 19) in renal tissue. In conclusion, current study obviously confirms the alleviating effects of Gum supplementation against AFB1-induced renal dysfunction, oxidative harm, inflammation, and cell death. These mitigating effects are suggested to be attributed to Gum's antioxidant and anti-inflammatory activities. Our results recommend Gum supplementation as add-on agents to food that might aid in protection from AFB1-induced nephrotoxicity

Tumor necrosis factor-alfa and monocyte chemoattractant protein-1 gene polymorphisms in kidney transplant recipients

Tumor necrosis factor-alfa (TNF-α) gene polymorphism is supposed to have a significant influence on the incidence of acute rejection in renal transplantation. The monocyte chemoattractant protein-1 (MCP-1) is another factor supposed to modulate graft rejection. We studied TNF-α and MCP-1 gene polymorphisms in 84 kidney allograft recipients with polymerase chain reaction and restriction fragment length polymorphism and their serum levels by enzyme-linked immunosorbent assay. The patients were classified into two groups based on their outcomes: Group I (n = 47) recipients with stable graft function as the control group and group II (n=37) recipients who experienced acute graft rejection episodes in the first 30 days post-transplantation. A significantly higher incidence of TNF 2 /TNF 2 genotype was observed among patients with acute graft rejection in comparison with the control group (40.5% and 19.2% respectively, P <0.05), while no statistically significant differences were observed in the TNF 1 /TNF 1 genotype between the groups (59.4% and 80.8%, respectively, P >0.05). A significant elevation of serum TNF-α levels was found in group II than group I and between TNF 2 genotype compared with that of TNF1 genotype within group II recipients. Distribution of MCP-1 genotypes in patients with and without acute rejection episodes was not significantly different (70.2% and 76.6% for MCP-1 A/A and 29.7% and 23.4% for MCP-1 G/G, respectively, P >0.05). The serum MCP-1 levels were not significantly different between the groups and between MCP-1 G/G genotype and MCP-1 A/A genotype in group II recipients. In conclusion, TNF-α gene polymorphism or its serum levels may identify patients at risk of acute rejection, where patients with TNF 2 /TNF 2 genotype or high serum TNF-α levels are more likely to have acute rejection episodes, while there was no relation between MCP-1 genotype or its serum levels and acute rejection