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

Mechanistic insights into carbonic anhydrase IX inhibition by coumarins from Calendula officinalis: in vitro and in silico approaches †

Given the critical role of carbonic anhydrase IX (CA IX) in various pathological conditions, there is a significant demand for new inhibitors to enhance patient outcomes and clinical management. In this study, we examined the inhibitory effectiveness of five coumarins derived from Calendula officinalis against CA IX using in vitro assays and computational modeling. Among the coumarins tested, xeroboside and isobaisseoside were identified as the most potent inhibitors. Kinetic studies indicated that xeroboside and isobaisseoside exhibit a mixed inhibition mode. Molecular docking analysis showed that the tested coumarins exhibit binding affinities and extensive polar interactions with CA IX. These coumarins demonstrated significant hydrophobic interactions and occupied the same binding site as acetazolamide (AAZ). Molecular dynamics (MD) indicated that xeroboside and isobaisseoside exhibited consistent trajectories and notable energy stabilization during their interaction with CA IX. MM/PBSA calculations showed that xeroboside displayed the lowest binding free energy (−27.26 ± 2.48 kJ mol−1). Potential Energy Landscape (PEL) analysis revealed distinct and stable conformational states for the CA IX–ligand complexes, with xeroboside exhibiting the most stable and lowest energy configuration. These computational findings are consistent with the experimental results, highlighting the potential efficacy of xeroboside and isobaisseoside as CA IX inhibitors. In conclusion, Calendula officinalis-derived coumarins are promising candidates as effective CA IX inhibitors

Oxidative Stress, Inflammation, and Altered Lymphocyte E-NTPDase Are Implicated in Acute Dyslipidemia in Rats: Protective Role of Arbutin

Background/Objectives: Dyslipidemia is frequently linked to various disorders, and its clinical relevance is now recognized. The role of inflammation and oxidative stress (OS) in dyslipidemia has been acknowledged. This study assessed the potential of arbutin (ARB) to prevent dyslipidemia and its associated OS and inflammation in rats with acute hyperlipidemia. Methods: Rats received ARB orally for 14 days and a single intraperitoneal injection of poloxamer-407 on day 15. Results: Poloxamer-407 elevated circulating cholesterol (CHOL), triglycerides (TG), very low-density lipoprotein (vLDL), and LDL, and reduced high-density lipoprotein (HDL)-C and lipoprotein lipase (LPL). ARB ameliorated the circulating lipids and LPL, and suppressed 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR) in rat liver and in vitro. Fatty acid synthase (FAS) in rat liver and its in vitro activity were suppressed by ARB, which also upregulated the LDL receptor (LDL-R) and ABCA1, and had no effect on ABCG5 and ABCG8 mRNA. ARB ameliorated liver malondialdehyde and nitric oxide and enhanced antioxidants in rats with dyslipidemia. Liver NF-κB p65 and blood inflammatory cytokines were increased in dyslipidemic rats, effects that were reversed by ARB. Moreover, ARB effectively suppressed lymphocyte E-NTPDase and E-ADA activities in dyslipidemic rats. The biochemical findings were supported by in silico data showing the affinity of ARB to bind LDL-R PCSK9 binding domain, HMGCR, FAS, and E-NTPDase. Conclusions: ARB possessed anti-dyslipidemia, anti-inflammatory, and antioxidant effects mediated via the modulation of CHOL and TG synthesis, LPL, lymphocyte E-NTPDase and E-ADA, and cytokine release in rats. Thus, ARB could be an effective agent to attenuate dyslipidemia and its associated OS and inflammation, pending further studies as well as clinical trials

Perceived responsibility for mechanical ventilation and weaning decisions in intensive care units in the Kingdom of Saudi Arabia

Background: Optimizing patient outcomes and reducing complications require constant monitoring and effective collaboration among critical care professionals. The aim of the present study was to describe the perceptions of physician directors, respiratory therapist managers and nurse managers regarding the key roles, responsibilities and clinical decision-making related to mechanical ventilation and weaning in adult Intensive Care Units (ICUs) in the Kingdom of Saudi Arabia (KSA). Methods: A multi-centre, cross-sectional self-administered survey was sent to physician directors, respiratory therapist managers and nurse managers of 39 adult ICUs at governmental tertiary referral hospitals in 13 administrative regions of the KSA. The participants were advised to discuss the survey with the frontline bedside staff to gather feedback from the physicians, respiratory therapists and nurses themselves on key mechanical ventilation and weaning decisions in their units. We performed T-test and non-parametric Mann-Whitney U tests to test the physicians, respiratory therapists, and nurses’ autonomy and influence scores, collaborative or single decisions among the professionals. Moreover, logistic regressions were performed to examine organizational variables associated with collaborative decision-making. Results: The response rate was 67% (14/21) from physician directors, 84% (22/26) from respiratory therapist managers and 37% (11/30) from nurse managers. Physician directors and respiratory therapist managers agreed to collaborate significantly in most of the key decisions with limited nurses’ involvement (P<0.01). We also found that physician directors were perceived to have greater autonomy and influence in ventilation and waning decision-making with a mean of 8.29 (SD±1.49), and 8.50 (SD±1.40), respectively. Conclusion: The key decision-making was implemented mainly by physicians and respiratory therapists in collaboration. Nurses had limited involvement. Physician directors perceived higher autonomy and influence in ventilatory and weaning decision-making than respiratory therapist managers and nurse managers. A critical care unit’s capacity to deliver effective and safe patient care may be improved by increasing nurses’ participation and acknowledging the role of respiratory therapists in clinical decision-making regarding mechanical ventilation and weaning

Public Knowledge, Attitudes, and Practice towards COVID-19 Pandemic in Saudi Arabia: A Web-Based Cross-Sectional Survey

(1) Background: COVID-19 has become a worldwide public health problem. No previous study has investigated factors associated with COVID-19 knowledge, attitude, and practice (KAP) after completely lifting the curfew in all Saudi Arabia regions and cities. Therefore, adequate knowledge, a positive attitude, and correct control of COVID-19 are essential to eradicate the disease. Hence, this study aims to assess factors associated with KAP of COVID-19; (2) Methods: This cross-sectional web-based survey was performed with the participation of 4305 individuals aged over 15 years living in Saudi Arabia from 11 to 19 August 2020. They were included using the snowball sampling method; (3) Results: Of the 4305 participants, 94.9% were Saudis, 60% females, and 45.4% were in the age group of 20–34 years, 61.7% married, and 49.3% from the Eastern Province of Saudi Arabia. Most of the participants demonstrated good KAP levels (89.6%, 87.2%, and 87.2%) towards the COVID-19 pandemic, respectively. In addition, most of the participants (85.8%) used the internet and social media as a source for COVID-19 information (4) Conclusions: The finding showed that most of the participants demonstrated good knowledge of COVID-19, positive attitudes, and demonstrated good practices for preventing the spread of disease infection

Tamarix articulata Induced Prevention of Hepatotoxicity Effects of In Vivo Carbon Tetrachloride by Modulating Pro-Inflammatory Serum and Antioxidant Enzymes to Reverse the Liver Fibrosis

This study evaluates the hepatoprotective activity of a Tamarix articulata extract against carbon tetrachloride-mediated hepatotoxicity in Wistar rats. Our results demonstrated that the oral administration of Tamarix articulata extract (50 mg/kg b.w.) significantly restored the serum levels of liver enzymes and antioxidant parameters (superoxide dismutase, catalase, glutathione reductase, and thiobarbituric reactive substances). Histopathology analysis revealed that Tamarix articulata extract significantly reduced hepatic fibrosis by inhibiting the necrosis of hepatocytes. Furthermore, serum pro-inflammatory (tumor necrosis factor-alpha, tumor growth factor-beta, and interleukin-6) markers were significantly restored. However, the anti-inflammatory cytokine adiponectin levels increased to normal levels in the group treated with Tamarix articulata extract. Additionally, we observed diminished reactive oxygen species production and the depolarization of mitochondrial membrane potential in hepatocytes extracted from animal livers treated with Tamarix articulata extract. Our findings suggest that Tamarix articulata extract prevents liver fibrosis induced by carbon tetrachloride and decreases the necrotic population of hepatocytes. These events restored the antioxidant enzymatic activity, serum levels of liver enzymes, and pro-inflammatory markers to their normal levels

Therapeutic Versus Preventative Use of <i>Ginkgo biloba</i> Extract (EGb 761) against Indomethacin-Induced Gastric Ulcer in Mice

The main bioactive constituents in the standardized Ginkgo biloba leaf extract (EGb 761) are the terpene lactones and flavonoid glycosides. EGb 761’s antioxidant and anti-inflammatory properties have previously been demonstrated. Indomethacin-induced gastric ulcers have a multifactorial etiology and represent a major restriction to its therapeutic utility. The underlying ulcerogenic process involves oxidative and inflammatory biomolecular insults. This study was performed to explore the curative and preventative benefits of EGb 761 in experimentally-induced ulcers. To develop gastric ulcers in mice, indomethacin (40 mg/kg) was administered orally. EGb 761 (200 mg/kg) was given by gavage for 7 days before (preventative) and after (therapeutic) indomethacin administration. The histological alterations and macroscopic mucosal lesions were assessed. In gastric tissue homogenates, malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), and inflammatory cytokines were measured. The expressions of cyclooxygenase-2 (COX-2), cytokines, and proliferating cell nuclear antigen (PCNA) in the stomach mucosa were also investigated. The ulcer index, histological alterations, gastric oxidants, and inflammatory biomarkers were all significantly increased by indomethacin. In stomach specimens, it increased COX-2 and PCNA expression. EGb 761 treatments, both prophylactic and therapeutic, resulted in significant reductions in ulcer lesions, nitrosative and oxidative damage, and inflammatory markers, along with the lowering of COX-2 and PCNA expressions. Furthermore, in the fight against stomach ulcers, EGb 761 treatment was found to be more efficient than prevention

Haloxylon salicornicum Phytochemicals Suppress NF‐kB, iNOS and Pro‐inflammatory Cytokines in Lipopolysaccharide‐Induced Macrophages

Haloxylon salicornicum is traditionally used for the treatment of several disorders associated with inflammation. Despite it is a defense response against tissue injury and infections, inflammation can become a chronic condition that can negatively impact the body. This study investigated the effect of H. salicornicum phytochemicals nuclear factor‐kappaB (NF‐κB), inducible nitric oxide synthase (iNOS) and cytokines release by lipopolysaccharide (LPS)‐challenged macrophages in vitro. The binding affinity of the tested phytochemical towards NF‐κB and iNOS was investigated using molecular docking. Ten compounds (four coumarins, three sterols and three flavonoids) were isolated from the ethanolic extract of H. salicornicum. Treatment of LPS‐challenged macrophages with the compounds resulted in remarkable decrease in NF‐κB p65 and iNOS mRNA abundance. All compounds suppressed the production of nitric oxide (NO) and the pro‐inflammatory cytokines (tumor necrosis factor (TNF)‐α and interleukin (IL)‐6) from macrophages challenged with LPS. Molecular docking revealed the ability of the isolated phytochemicals to bind NF‐κB p65 and iNOS. In conclusion, H. salicornicum is a rich source of phytochemicals with anti‐inflammatory properties. The anti‐inflammatory efficacy of H. salicornicum phytoconstituents is mediated via their ability to modulate NF‐κB and iNOS, and suppress the release of NO, TNF‐α, and IL‐6 from macrophages

Detection of β-Lactamase Resistance and Biofilm Genes in <i>Pseudomonas</i> Species Isolated from Chickens

Bacteria of the genus Pseudomonas are pathogens in both humans and animals. The most prevalent nosocomial pathogen is P. aeruginosa, particularly strains with elevated antibiotic resistance. In this study, a total of eighteen previously identified Pseudomonas species strains, were isolated from chicken. These strains were screened for biofilm formation and antibiotic resistance. In addition, we evaluated clove oil’s effectiveness against Pseudomonas isolates as an antibiofilm agent. The results showed that Pseudomonas species isolates were resistant to most antibiotics tested, particularly those from the β-lactamase family. A significant correlation (p AmpC-plasmid-mediated genes (blaCMY, blaMIR, DHA, and FOX) and biofilm-related genes (psld, rhlA, and pelA) in most of our isolates, PCR confirmed this relationship. Clove oil has a potent antibiofilm effect against Pseudomonas isolates, and may provide a treatment for bacteria that form biofilms and are resistant to antimicrobials

Design, Physical Characterizations, and Biocompatibility of Cationic Solid Lipid Nanoparticles in HCT-116 and 16-HBE Cells: A Preliminary Study

In this study, pEGFP-LUC was used as a model plasmid and three distinct cationic lipids (dioleyloxy-propyl-trimethylammonium chloride [DOTMA], dioleoyl trimethylammonium propane [DOTAP], and cetylpyridinium chloride [CPC]) were tested along with PEG 5000, as a nonionic surfactant, to prepare glyceryl monostearate (GMS)-based cationic solid lipid nanoparticles (cSLNs). Both the type and quantity of surfactant had an impact on the physicochemical characteristics of the cSLNs. Thermal analysis of the greater part of the endothermic peaks of the cSLNs revealed they were noticeably different from the individual pure compounds based on their zeta potential (ZP ranging from +17 to +56 mV) and particle size (PS ranging from 185 to 244 nm). The addition of cationic surfactants was required to produce nanoparticles (NPs) with a positive surface charge. This suggested that the surfactants and extensive entanglement of the lipid matrix GMS provided support for the behavioral diversity of the cSLNs and their capacity to interface with the plasmid DNA. Additionally, hemolytic assays were used to show that the cSLNs were biocompatible with the human colon cancer HCT-116 and human bronchial epithelial 16-HBE cell lines. The DOTMA 6-based cSLN was selected as the lead cSLN for further ex vivo and in vivo investigations. Taken together, these new findings might provide some guidance in selecting surfactants to prepare extremely efficient and non-toxic cSLN-based therapeutic delivery systems (e.g., gene therapy)