Caveolin-1's dual impact on endometrioid endometrial carcinoma: a histopathological and immunohistochemical study.

The objectives of this study are to evaluate caveolin-1 expression in endometrioid endometrial cancer and its correlation with clinicopathological parameters. Forty-four cases of endometrioid endometrial carcinomas underwent radical hysterectomy. The archived paraffin sections that were stained for caveolin-1 by immunohistochemistry, caveolin-1 expression were detected in cancerous epithelial cells in 18.2% of the cases, and stromal caveolin-1 was detected in 65.9% of the cases. Caveolin-1 expression in the epithelium showed a significant positive association with the T stage and the FIGO stage. Positive caveolin-1 expression in epithelium has a direct, positive and significant relationship with invasion of other organs and a direct and significant relationship with the advanced FIGO stage. As for caveolin-1 expression in the stroma, it showed a significant negative inversely significant association with myometrial invasion. Also, there is a significant negative association between caveolin-1 expression in the epithelium and its expression in the stroma. We conclude that caveolin-1 expression strongly plays a critical role in endometrioid endometrial carcinoma as a tumor suppressor or promoter of invasion. In early lesions, high stromal levels appear to be protective against progression. While decreased stromal expression and increased epithelial expression were associated with aggressive tumors.

Reno-protective effect of fenofibrate and febuxostat against vancomycin-induced acute renal injury in rats: Targeting PPARγ/NF-κB/COX-II and AMPK/Nrf2/HO-1 signaling pathways.

BACKGROUND: Vancomycin (VCM) is used clinically to treat serious infections caused by multi-resistant Gram-positive bacteria, although its use is severely constrained by nephrotoxicity. This study investigated the possible nephroprotective effect of febuxostat (FX) and/or fenofibrate (FENO) and their possible underlying mechanisms against VCM-induced nephrotoxicity in a rat model. METHODS: Male Wistar rats were randomly allocated into five groups; Control, VCM, FX, FENO, and combination groups. Nephrotoxicity was evaluated histopathologically and biochemically. The oxidative stress biomarkers (SOD, MDA, GSH, total nitrite, GPx, MPO), the apoptotic marker, renal Bcl-2 associated X protein (Bax), and inflammatory and kidney injury markers (IL-1ß, IL-6, TNF-α, Nrf2, OH-1, kappa-light-chain-enhancer of activated B cells (NF-κB), NADPH oxidase, Kim-1, COX-II, NGAL, Cys-C were also evaluated. RESULTS: VCM resulted in significant elevation in markers of kidney damage, oxidative stress, apoptosis, and inflammatory markers. Co-administration of VCM with either/or FX and FENO significantly mitigated nephrotoxicity and associated oxidative stress, inflammatory and apoptotic markers. In comparison to either treatment alone, a more notable improvement was observed with the FX and FENO combination regimen. CONCLUSION: Our findings show that FX, FENO, and their combination regimen have a nephroprotective impact on VCM-induced kidney injury by suppressing oxidative stress, apoptosis, and the inflammatory response. Renal recovery from VCM-induced injury was accomplished by activation of Nrf2/HO-1 signaling and inhibition of NF-κB expression. This study highlights the importance of FX and FENO as effective therapies for reducing nephrotoxicity in VCM-treated patients.

Arabincoside B isolated from Caralluma arabica as a potential anti-pneumonitis in LPS mice model.

Acute lung injury (ALI) is a life-threatening condition usually associated with poor therapeutic outcomes and a high mortality rate. Since 2019, the situation has worsened due to the COVID-19 pandemic. ALI had approximately 40% of deaths before COVID-19, mainly due to the dysfunction of the blood-gas barrier that led to lung edema, failure of gas exchange, and dyspnea. Many strategies have been taken to mitigate the disease condition, such as diuretics, surfactants, antioxidants, glucocorticoids, heparin, and ventilators with concomitant sedatives. However, until now, there is no available effective therapy for ALI. Thus, we are presenting a new compound termed Arabincoside B (AR-B), recently isolated from Caralluma arabica, to be tested in such conditions. For that, the lipopolysaccharide (LPS) mice model was used to investigate the capability of the AR-B compound to control the ALI compared to standard dexamethasone. The results showed that AR-B had a significant effect on retrieving ALI. A further mechanistic study carried out in the serum, lung homogenate, histological, and immunohistochemistry sections revealed that the AR-B either in 50 mg/kg or 75 mg/kg dose inhibited pro-inflammatory cytokines such as IL-6, IL-13, NF-κB, TNFα, and NO and stimulated regulatory cytokines IL-10. Moreover, AR-B showed a considerable potential to protect the pulmonary tissue against oxidative stress by decreasing MDA and increasing catalase and Nrf2. Also, the AR-B exhibited an anti-apoptotic effect on the lung epithelium, confirmed by reducing COX and BAX expression and upregulating Bcl-2 expression. These results pave its clinical application for ALI.

Bioactive fraction from Plumeria obtusa L. attenuates LPS-induced acute lung injury in mice and inflammation in RAW 264.7 macrophages: LC/QToF-MS and molecular docking.

In this study, the anti-inflammatory effects of the methanolic extract (TE) of Plumeria obtusa L. (aerial parts) and its fractions were evaluated in vitro, and active fraction was evaluated in vivo. Among tested extracts, dichloromethane fraction (DCM-F) exhibited the strongest inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) in RAW 264.7 macrophages. The effect of DCM-F on LPS-induced acute lung injury (ALI) in mice was studied. The animals were divided into five groups (n = 7) randomly; Gp I: negative control, GP II: positive control (LPS group), GP III: standard (dexamethasone, 2 mg/kg b.wt), GP IV and V: DCM-F (100 mg/kg), and DEM-F (200 mg/kg), respectively. DCM-F at a dose of 200 mg/kg suppressed the ability of LPS to increase the levels of nitric oxide synthase (iNOS), NO, tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6), as measured by ELISA. In addition, the expression of cyclooxygenase-2 (COX-2) was reduced (determined by immunohistochemistry) and the level of malondialdehyde (MDA) was decreased while that of catalase was restored to the normal values. Furthermore, the histopathological scores of inflammation induced by LPS were reduced. Twenty-two compounds were tentatively identified in DCM-F using LC/ESI-QToF with iridoids, phenolic derivatives and flavonoids as major constituents. Identified compounds were subjected to two different molecular docking processes against iNOS and prostaglandin E synthase-1 target receptors. Notably, protoplumericin A and 13-O-coumaroyl plumeride were the most promising members compared to the co-crystallized inhibitor in each case. These findings suggested that DCM-F attenuates the LPS-induced ALI in experimental animals through its anti-inflammatory and antioxidant potential.

Ameliorative effect of vitamin E and selenium against bisphenol A-induced toxicity in spinal cord and submandibular salivary glands of adult male albino rats.

Bisphenol A (BPA) used in plastic industry. This study evaluate ameliorative effect of vitamin E and selenium in combating BPA toxicity in spinal cord (SC) and submandibular glands (SMGs). Thirty rats divided into three groups [Group I, controls; Group II, BPA orally (25 mg/kg) three times a week, 60 days; Group III, BPA (25 mg/kg) plus vitamin E and selenium in water (1 ml/L/day)]. By histopathological, immunohistochemical, and biochemical investigations. Bisphenol A group showed degenerative alterations. SC gray matter showed pyknotic nuclei and white matter revealed neuropil degeneration. Myelinated fibers showed dispersed myelin. SMGs, exhibited vacuolated cytoplasm in acinar cells. Intense glial fibrillary acidic protein in SC and strong proliferating cell nuclear antigen in acinar and ductal cell nuclei of SMGs. Malondialdehyde elevated in SC and catalase decreased in SMG. Group III, SC and SMG revealed partial recovery. Vitamin E and selenium displayed protective effects against BPA toxicity in SC and SMGs.

BPA had a neurotoxic effect on spinal cord of albino rats.BPA causing degeneration of nerve fibers with axonal disappearance of white matter.BPA caused GFAP proliferation and high MDA level in spinal cord.BPA caused degeneration of submandibular gland's acinar cells and duct system.Both vitamin E and Selenium had a protective effect against BPA toxicity.

Screening for polystyrene nanoparticle toxicity on kidneys of adult male albino rats using histopathological, biochemical, and molecular examination results.

Polystyrene Nanoparticles (PS-NPs) used for packaging foam, disposable cups, and food containers. Therefore, this study aimed to evaluate PS- NPs toxic effects on kidney of adult male albino rats. A total of 30 rats divided into three groups (n = 10): group I negative control group; group II orally administered 3% PS-NPs (3 mg/kg body weight/day) and group III orally administered 3% PS-NPs (10 mg/kg body weight/day) for 35 days. Blood and kidney samples collected and processed for biochemical, histopathological, and immunohistochemical examinations. Results showed that low and high doses PS-NPs had significantly increased serum blood urea nitrogen (BUN), creatinine, malondialdehyde, significantly further reduced glutathione, downregulation of nuclear factor erythroid 2-related factor 2 and glutathione peroxidase, upregulation of caspase-3 and Cytochrome-c. Histopathological examination revealed several alterations. Low dose of PS-NPs exhibited dilated glomerular capillaries, hypotrophy of some renal corpuscles significantly decreases their diameter to 62 µm. Some proximal convoluted tubules and distal convoluted tubules showed loss of cellular architecture with pyknotic nuclei. Hyalinization and vacuolation in renal medulla. In high dose PS-NPs, alterations increased in severity. A significant increase in percentage area of cyclooxygenase-2 in low and high-doses. In conclusion, PS-NPs are a nephrotoxic causing renal dysfunction.

Antitumor and multikinase inhibition activities of some synthesized coumarin and benzofuran derivatives.

Two new series of coumarin and benzofuran derivatives were designed, synthesized, and assessed for their in vitro and in vivo antitumor activities against breast cancer. Compounds 8, 9, 14, 15, and 17 exhibited the best antiproliferative activities (IC50 : 0.07-2.94 µM) against the MCF-7 cell line, compared with lapatinib (IC50 : 4.69 µM). Compound 14, with the most potent cytotoxic activity against MCF-7 cells, was capable of enhancing preG1 apoptosis and triggering cell cycle arrest at the G2/M phase. The kinase inhibitory activity of compound 14 against a panel of 22 kinases was examined to reveal multikinase inhibition within -39% to -97%. Furthermore, compound 14 exhibited potent in vivo Ehrlich (mammary adenocarcinoma) tumor regression, positive caspase-3, and negative EGFR immunoreaction, and was capable of elevating the catalase level. The physicochemical properties and pharmacokinetic parameters of compound 14 were investigated in silico for its druglikeness.

Development and Greenness Assessment of HPLC Method for Studying the Pharmacokinetics of Co-Administered Metformin and Papaya Extract.

Foods with medical value have been proven to be beneficial, and they are extensively employed since they integrate two essential elements: food and medication. Accordingly, diabetic patients can benefit from papaya because the fruit is low in sugar and high in antioxidants. An RP-HPLC method was designed for studying the pharmacokinetics of metformin (MET) when concurrently administered with papaya extract. A mobile phase of 0.5 mM of KH2PO4 solution and methanol (65:35, v/v), pH = 5 ± 0.2 using aqueous phosphoric acid and NaOH, and guaifenesin (GUF) were used as an internal standard. To perform non-compartmental pharmacokinetic analysis, the Pharmacokinetic program (PK Solver) was used. The method's greenness was analyzed using two tools: the Analytical GREEnness calculator and the RGB additive color model. Taking papaya with MET improved the rate of absorption substantially (time for reaching maximum concentration (Tmax) significantly decreased by 75% while maximum plasma concentration (Cmax) increased by 7.33%). The extent of absorption reduced by 22.90%. Furthermore, the amount of medication distributed increased (30.83 L for MET concurrently used with papaya extract versus 24.25 L for MET used alone) and the clearance rate rose by roughly 13.50%. The results of the greenness assessment indicated that the method is environmentally friendly. Taking papaya with MET changed the pharmacokinetics of the drug dramatically. Hence, this combination will be particularly effective in maintaining quick blood glucose control.

Detecting liver fibrosis using a machine learning-based approach to the quantification of the heart-induced deformation in tagged MR images.

Liver disease causes millions of deaths per year worldwide, and approximately half of these cases are due to cirrhosis, which is an advanced stage of liver fibrosis that can be accompanied by liver failure and portal hypertension. Early detection of liver fibrosis helps in improving its treatment and prevents its progression to cirrhosis. In this work, we present a novel noninvasive method to detect liver fibrosis from tagged MRI images using a machine learning-based approach. Specifically, coronal and sagittal tagged MRI imaging are analyzed separately to capture cardiac-induced deformation of the liver. The liver is manually delineated and a novel image feature, namely, the histogram of the peak strain (HPS) value, is computed from the segmented liver region and is used to classify the liver as being either normal or fibrotic. Classification is achieved using a support vector machine algorithm. The in vivo study included 15 healthy volunteers (10 males; age range 30-45 years) and 22 patients (15 males; age range 25-50 years) with liver fibrosis verified and graded by transient elastography, and 10 patients only had a liver biopsy and were diagnosed with a score of F3-F4. The proposed method demonstrates the usefulness and efficiency of extracting the HPS features from the sagittal slices for patients with moderate fibrosis. Cross-validation of the method showed an accuracy of 83.7% (specificity = 86.6%, sensitivity = 81.8%).

Contrast-Enhanced Ultrasound Guidance for Interventional Procedures.

Since its introduction, contrast-enhanced ultrasound (CEUS) has gained an important role in the diagnosis and management of abdominal and pelvic diseases. Contrast-enhanced ultrasound can improve lesion detection rates as well as success rates of interventional procedures when compared to conventional ultrasound alone. Additionally, CEUS enables the interventionalist to assess the dynamic enhancement of different tissues and lesions, without the adverse effects of contrast-enhanced computed tomography, such as exposure to ionizing radiation and nephrotoxicity from iodinated contrast material. This review article describes the various applications and advantages of the use of CEUS to enhance performance of ultrasound-guided interventions in the abdomen and pelvis.

Trans-abdominal ultrasound shear wave elastographyfor quantitative assessment of female bladder neck elasticity.

INTRODUCTION AND HYPOTHESIS: Disorders of micturition result from a wide variety of conditions and evaluation often involves multiple diagnostic modalities. However, the sensitivity and specificity of these techniques are highly variable and may not always yield a diagnosis. Novel imaging techniques such as ultrasound shear wave elastography may help to improve diagnostic accuracy. METHODS: Continent women were recruited from outpatient gynecology offices from a tertiary medical system. Participants underwent ultrasound evaluation with measurement of the shear wave velocity (SWV) of the bladder neck (BN). SWV was used to determine the Young's modulus of the bladder neck. The median bladder neck stiffness was calculated and univariate and step-wise and backward multivariate logistic regression analyses were used to identify significant patient characteristics associated with bladder neck stiffness above or below the median. RESULTS: Fifty-seven women underwent SWE of the bladder; 12 were excluded, and 45 were included in the analysis. The median bladder neck stiffness of the study population was 22 (17.1-28.2) kPa. Age greater than 45 years was associated with a bladder neck stiffness above the median, OR 8.39, p < 0.001. Having no vaginal deliveries was also associated with a bladder neck stiffness greater than 22 kPa, unadjusted OR 4.76 (95 % CI 1.41-20.0, p = 0.012). Bladder volume and bladder neck thickness were not significantly associated with bladder neck stiffness above or below the median. CONCLUSION: Trans-abdominal shear wave elastography can be used to quantitatively assess bladder neck stiffness. This technique may potentially be useful for evaluating chronic urinary retention.

Is Ultrasound Fusion a Reasonable Replacement for Computed Tomography in Guiding Abdominal Interventions?

OBJECTIVES: To compare the diagnostic yield, complication rate, and procedure length of ultrasound fusion-guided liver biopsy to the diagnostic yield, complication rate, and procedure length of computed tomography (CT)-guided liver biopsy; to measure the average ionizing radiation dose that patients are exposed to during a typical CT-guided liver biopsy procedure; and to present relevant and interesting cases of ultrasound fusion-guided abdominal interventions to describe the efficacious use of the technology. METHODS: A retrospective analysis of 63 patients who had image-guided liver biopsies performed at our institution was completed. Patient records were divided into 2 groups according to the type of image guidance used during the procedure (ultrasound fusion versus CT), and data were compared by the χ(2) test, Student t test, and Mann-Whitney U test. RESULTS: The diagnostic yields and complication rates were not statistically significantly different between the modalities. The average procedure durations were significantly different: ultrasound fusion-guided biopsy, 31.63 minutes; compared to CT-guided biopsy, 61.67 minutes (P = .003). CONCLUSIONS: Diagnostic yields and complication rates were comparable for ultrasound fusion and CT. However, the average procedure duration for an ultrasound fusion-guided liver biopsy was approximately half that of CT-guided liver biopsy, likely increasing both cost-effectiveness and patient satisfaction.

Preparation and characterization of Sorafenib nano-emulsion: impact on pharmacokinetics and toxicity; an in vitro and in vivo study.

Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer-related deaths worldwide. Current treatment strategies include surgical resection, liver transplantation, liver-directed therapy, and systemic therapy. Sorafenib (Sor) is the first systemic drug authorized by the US Food and Drug Administration (FDA) for HCC treatment. Nevertheless, the conventional oral administration of Sor presents several limitations: poor solubility, low bioavailability, drug resistance development, and off-target tissue accumulation, leading to numerous adverse effects. Nano-emulsion, a nano-delivery system, is a viable carrier for poorly water-soluble drugs. It aims to enhance drug bioavailability, target organ accumulation, and reduce off-target tissue exposure, thus improving therapeutic outcomes while minimizing side effects. This study formulated Sor nano-emulsion (Sor NanoEm) using the homogenization technique. The resultant nano-emulsion was characterized by particle size (121.75 ± 12 nm), polydispersity index (PDI; 0.310), zeta potential (-12.33 ± 1.34 mV), viscosity (34,776 ± 3276 CPs), and pH (4.38 ± 0.3). Transmission Electron Microscopy exhibited spherical nano-droplets with no aggregation signs indicating stability. Furthermore, the encapsulation of Sor within the nano-emulsion sustained its release, potentially reducing the frequency of therapeutic doses. Cytotoxicity assessments on the HepG2 cell line revealed that Sor NanoEm had a significantly (P < 0.05) more potent cytotoxic effect compared to Sor suspension. Subsequent tests highlighted superior pharmacokinetic parameters and reduced dosage requirements of Sor NanoEm in mice. It exhibited an enhanced safety profile, particularly in behavior, brain, and liver, compared to its suspended form. These findings underscore the enhanced pharmacological and toxicological attributes of Sor Nano-emulsion, suggesting its potential utility in HCC treatment.

Argel's stemmoside C as a novel natural remedy for mice with alcohol-induced gastric ulcer based on its molecular mechanistic pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Solenostemma argel is widely distributed in Africa & Asia with traditional usage in alleviating abdominal colic, aches, & cramps. This plant is rich in phytochemicals, which must be explored for its pharmacological effects. PURPOSE: Peptic Ulcer Disease (PUD) is the digestion of the digestive tube. PUD not only interferes with food digestion & nutrient absorption, damages one of the largest defensive barriers against pathogenic micro-organisms, but also impedes drug absorption & bioavailability, rendering the oral route, the most convenient way, ineffective. Omeprazole, one of the indispensable cost-effective proton-pump inhibitors (PPIs) extensively prescribed to control PUD, is showing growing apprehensions toward multiple drug interactions & side effects. Hence, finding a natural alternative with Omeprazole-like activity & limited side effects is a medical concern. STUDY DESIGN: Therefore, we present Stemmoside C as a new gastroprotective phytochemical agent isolated from Solenostemma argel to be tested in upgrading doses against ethanol-induced gastric ulcers in mice compared to negative, positive, & reference Omeprazole groups. METHODS: We carried out in-depth pharmacological & histopathological studies to determine the possible mechanistic pathway. RESULTS: Our results showed that Stemmoside C protected the stomach against ethanol-induced gastric ulcers parallel to Omeprazole. Furthermore, the mechanistic studies revealed that Stemmoside C produced its effect using an orchestrated array of different mechanisms. Stemmoside C stimulates stomach defense by increasing COX-2, PGE-2, NO, & TFF-1 healing factors, IL-10 anti-inflammatory cytokine, & Nrf-2 & HO-1 anti-oxidant pathways. It also suppresses stomach ulceration by inhibiting leucocyte recruitment, especially neutrophils, leading to subsequent inhibition of NF-κBp65, TNF-α, IL-1ß, & iNOS pro-inflammatory cytokines & JAK-1/STAT-3 inflammation-induced carcinogenicity cascade in addition to MMP-9 responsible for tissue degradation. CONCLUSION: These findings cast light on Stemmoside C's clinical application against gastric ulcer progression, recurrence, & tumorigenicity & concurrently with chemotherapy.

Combined diosmin and bisoprolol attenuate cobalt chloride-induced cardiotoxicity and endothelial dysfunction through modulating miR-143-3P/MAPK/MCP-1, ERK5/CXCR4, Orai-1/STIM-1 signaling pathways.

Even while accelerated cardiomyocyte apoptosis is one of the primary causes of cardiac damage, the underlying mechanism is still mostly unknown. In addition to examining potential protective effects of bisoprolol and diosmin against CoCl2-induced cardiac injury, the goal of this study was to identify potential mechanisms regulating the hypoxic cardiac damage caused by cobalt chloride (CoCl2). For a period of 21 days except Cocl2 14 days from the first day of the experiment, rats were split into the following groups: Normal control group, rats received vehicle only (2 ml/kg/day, p.o.), (Cocl2, 150 mg/kg/day, p.o.), bisoprolol (25 mg/kg/day, p.o.); diosmin (100 mg/kg/day, p.o.) and bisoprolol + diosmin + Cocl2 groups. At the end of the experimental period, serum was taken for estimation of cardiac function, lipid profile, and pro/anti-inflammatory cytokines. Moreover, tissue samples were collected for evaluation of oxidative stress, endothelial dysfunction, α-SMA, PKC-α, MiR-143-3P, MAPK, ERK5, MCP-1, CXCR4, Orai-1, and STIM-1. Diosmin and bisoprolol, either alone or in combination, enhance heart function by reducing abnormalities in the electrocardiogram and the hypotension brought on by CoCl2. Additionally, they significantly ameliorate endothelial dysfunction by downregulating the cardiac expressions of α-SMA, PKC-α, MiR-143-3P, MAPK, ERK5, MCP-1, CXCR4, Orai-1, and STIM-1. Bisoprolol and diosmin produced modulatory activity against inflammatory state, redox balance, and atherogenic index concurrently. Together, diosmin and bisoprolol, either alone or in combination, significantly reduced all the cardiac alterations brought on by CoCl2. The capacity to obstruct hypoxia-induced α-SMA, PKC-α, MiR-143-3P/MAPK/MCP-1, MiR-143-3P/ERK5/CXCR4, Orai-1/STIM-1 signaling activation, as well as their anti-inflammatory, antioxidant, and anti-apoptotic properties, may be responsible for these cardio-protective results.

Combined ß-sitosterol and trimetazidine mitigate potassium dichromate-induced cardiotoxicity in rats through the interplay between NF-κB/AMPK/mTOR/TLR4 and HO-1/NADPH signaling pathways.

Hexavalent chromium salt, like potassium dichromate (PD), is chromium's most precarious valence state in industrial wastes. Recently, there has been increasing interest in ß-sitosterol (BSS), a bioactive phytosterol, as a dietary supplement. BSS is recommended in treating cardiovascular disorders due to its antioxidant effect. Trimetazidine (TMZ) was used traditionally for cardioprotection. Through the administration of BSS and TMZ, the cardiotoxic effects of PD were to be countered in this study, in addition to examining the precise mechanism of PD-induced cardiotoxicity. Thirty male albino rats were divided into five groups; the control group: administered normal saline daily (3 mL/kg); the PD group: administered normal saline daily (3 mL/kg); BSS group: administered BSS daily (20 mg/kg); TMZ group: administered TMZ daily (15 mg/kg); and the BSS + TMZ group: administered both BSS (20 mg/kg) and TMZ (15 mg/kg) daily. All experimental groups, except the control, received on the 19th day a single dose of PD (30 mg/kg/day, S.C.). Normal saline, BSS, and TMZ were received daily for 21 consecutive days p.o. The exposure to PD promoted different oxidative stresses, pro-inflammatory, and cardiotoxicity biomarkers. BSS or TMZ succeeded solely in reducing these deleterious effects; however, their combination notably returned measured biomarkers close to normal values. The histopathological investigations have supported the biochemical findings. The combination of BSS and TMZ protects against PD cardiotoxicity in rats by reducing oxidative stress and apoptotic and inflammatory biomarkers. It may be promising for alleviating and protecting against PD-induced cardiotoxicity in people at an early stage; however, these findings need further clinical studies to be confirmed. HIGHLIGHTS: • Potassium dichromate induces cardiotoxicity in rats through the upregulation of oxidative stress, proinflammatory, and apoptotic pathways biomarkers. • ß-Sitosterol possesses a possible cardioprotective effect by modulating several signaling pathways. • Trimetazidine, the antianginal agent, has a potential cardioprotective impact on PD-intoxicated rat model. • The combination of ß-Sitosterol and trimetazidine was the best in modulating different pathways involved in PD cardiotoxicity in rats via the interplay between NF-κB/AMPK/mTOR/TLR4 and HO-1/NADPH signaling pathways.

Effects of Aluminum Oxide Nanoparticles in the Cerebrum, Hippocampus, and Cerebellum of Male Wistar Rats and Potential Ameliorative Role of Melatonin.

Aluminum oxide nanoparticles (Al2O3 NPs) have been widely used in vaccine manufacture, food additives, human care products, and cosmetics. However, they also have adverse effects on different organs, including the liver, kidneys, and testes. Melatonin is a potent antioxidant, particularly against metals by forming melatonin-metal complexes. The present study aimed to investigate the protective effects of melatonin against Al2O3 NP-induced toxicity in the rat brain. Forty adult male Wistar rats were allocated to four groups: the untreated control (received standard diet and distilled water), Al2O3 NP-treated (received 30 mg/kg body weight Al2O3 NPs), melatonin and Al2O3 NP-treated (received 30 mg/kg body weight Al2O3 NPs + 10 mg/kg body weight melatonin), and melatonin-treated (received 10 mg/kg body weight melatonin) groups. All treatments were by oral gavages and administered daily for 28 days. Afterward, the rats were sacrificed, and samples from various brain regions (cerebrum, cerebellum, and hippocampus) were subjected to biochemical, histopathological, and immunohistochemical analyses. Al2O3 NPs substantially increased malondialdehyde, ß-amyloid 1-42 peptide, acetylcholinesterase, and ß-secretase-1 expression, whereas they markedly decreased glutathione levels. Furthermore, Al2O3 NPs induced severe histopathological alterations, including vacuolation of the neuropil, enlarged pericellular and perivascular spaces, vascular congestion, neuronal degeneration, and pyknosis. Al2O3 NP treatment also resulted in an intense positive caspase-3 immunostaining. Conversely, the administration of melatonin alleviated the adverse effects induced by Al2O3 NPs. Therefore, melatonin can diminish the neurotoxic effects induced by Al2O3 NPs.

Assessment of the neuroprotective effect of selenium-loaded chitosan nanoparticles against silver nanoparticles-induced toxicity in rats.

BACKGROUND: With the recent growth in the applications of silver nanoparticles (Ag-NPs), worries about their harmful effects are increasing. Selenium plays a vital role in the antioxidant defense system as well as free radical scavenging activity. OBJECTIVES: This study aims to inspect the neuroprotective effect of selenium-loaded chitosan nanoparticles (CS-SeNPs) against the adverse impact of Ag-NPs on brain tissue in adult rats. DESIGN: Rats were divided into four groups: group I (control) was administered distilled water (0.5 mL/kg), group II was administered Ag-NPs (100 mg/kg), group III was administered Ag-NPs (100 mg/kg) and CS- SeNPs (0.5 mg/kg) and group IV received only CS- SeNPs (0.5 mg/kg) daily by oral gavage. After 60 days, rats were subjected to behavioral assessment and then euthanized. Brain tissues were obtained for estimation of total antioxidant capacity (TAC), malondialdehyde (MDA), 8-hydroxy-2-deoxy Guanosine (8-OHdG), and Nuclear Factor Erythroid 2 Like Protein 2 (Nrf2). Also, histological examination of the brain and immunohistochemical detection of glial fibrillary acidic protein (GFAP) were investigated RESULTS: exposure to Ag-NPs induced marked neurotoxicity in the brain tissue of rats that was manifested by decreased levels of TAC and Nrf2 with increased levels of MDA and 8-OHdG. Also, various pathological lesions with an increase in the number of GFAP immunoreactive cells were detected. While brain tissue of rats received Ag-NPs plus CS-SeNPs group (III) revealed significantly fewer pathological changes. CONCLUSION: Co-administration of CS-SeNPs significantly ameliorates most of the Ag-NPs-induced brain damage.

Awareness of Fixed Partial Dentures and Implant Rehabilitation of Missing Teeth Among a Subset of Saudi Population.

Background  Maintaining one's sense of self requires having healthy teeth. A person's physical well-being is greatly impacted by their dental health. They are intimately related, and the socioeconomic situation of the individual largely determines how teeth are maintained. As a result, tooth loss causes injury to the stomatognathic system as well as the masticatory function. Morale is negatively impacted by psychological discomfort as well as the reduction in general quality of life brought on by tooth loss. Objectives  The purpose of this study was to assess the awareness of patients about various dental prosthetic rehabilitative procedures in Saudi Arabia, their preference(s) regarding the choice of treatment, and the motivating factors that drive them to avail of dental prosthetic rehabilitative treatment. Methods  After randomly selecting 600 individuals for the purpose of our investigation, a nine-variable questionnaire was framed by investigators to record the responses of those who consented to participate in our study. Results  Only 68.3% of the respondents were found to be aware of the several prosthodontic replacement choices. As mentioned by the majority of the respondents, the cost element was the biggest drawback for replacement. The benefits of choosing fixed partial dentures (FPD) or dental implants were judged to be aesthetics (41.1%) and the feel of one's own teeth (40.1%). Conclusion Only 68.3% of respondents reported knowing about the several prosthodontic replacement choices. The cost aspect was cited by 348 respondents as the biggest drawback to replacement. The perceived benefits of choosing FPD or dental implants were deemed to be aesthetics (41.1%) and the feel of one's own teeth (40.1%). We believe that patients' health and quality of life can be improved by raising awareness about and changing patients' attitudes toward the most cutting-edge treatment options that are readily available. This can be done by educating people about the drawbacks of delaying the replacement of missing teeth and other treatment options.

Impact of buffered sodium butyrate as a partial or total dietary alternative to lincomycin on performance, IGF-1 and TLR4 genes expression, serum indices, intestinal histomorphometry, Clostridia, and litter hygiene of broiler chickens.

BACKGROUND: Sodium butyrate (SB) is a short-chain fatty acid and a safe antibiotic alternative. During 35 days, this study compared the impact of coated SB (Butirex C4) and lincomycin (Lincomix) on broiler growth, gut health, and litter hygiene in 1200 one-day-old Ross-308 broiler chicks that were randomly assigned into 5-dietary groups with 5-replications each. Groups divided as follows: T1: Basal diet (control), T2: Basal diet with buffered SB (1 kg/ton starter feed, 0.5 kg/ton grower-finisher feeds), T3: Basal diet with 100 g/ton lincomycin, T4: Basal diet with buffered SB (0.5 kg/ton starter feed, 0.25 kg/ton grower-finisher feeds) + 50 g/ton lincomycin, and T5: Basal diet with buffered SB (1 kg/ton starter feed, 0.5 kg/ton grower-finisher feeds) + 50 g/ton lincomycin. Birds were housed in a semi-closed deep litter house, where feed and water were available ad libitum. Results were statistically analyzed using ANOVA and Tukey's post hoc tests. RESULTS: Combined dietary supplementation with SB and lincomycin (T4 and T5) significantly enhanced body weights, weight gains, feed conversion ratio, and profitability index. Also, carcasses in T4 and T5 exhibited the highest dressing, breast, thigh, and liver yields. T5 revealed the best blood biochemical indices, while T3 showed significantly elevated liver and kidney function indices. T4 and T5 exhibited the highest expression levels of IGF-1 and TLR4 genes, the greatest villi length of the intestinal mucosa, and the lowest levels of litter moisture and nitrogen. Clostridia perfringens type A alpha-toxin gene was confirmed in birds' caeca, with the lowest clostridial counts defined in T4. CONCLUSIONS: Replacing half the dose of lincomycin (50 g/ton) with 0.5 or 1 kg/ton coated SB as a dietary supplement mixture showed the most efficient privileges concerning birds' performance and health.