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1.
Cureus ; 16(8): e66452, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39246955

ABSTRACT

Chronic kidney disease-associated pruritus (CKD-aP) represents a common distressing problem in patients with end-stage renal disease. This study aimed to assess the efficacy and safety of omega-3 supplementation in the treatment of CKD-aP. MEDLINE/PubMed, Cochrane Central Register of Controlled Trials, Web of Science, ProQuest, and Scopus databases were searched systematically for articles published from inception until May 21, 2024. Outcomes were pruritus severity at the end of the study or its change from baseline (primary) and intervention-related adverse effects (secondary). Results were pooled as standardized mean difference (SMD) and risk ratio (RR) for numeric and dichotomous outcomes, respectively, along with their 95% confidence intervals (CIs). Eight studies were included. Treatment with omega-3 fatty acids showed a significantly lower severity of CKD-aP at the end of treatment (pooled SMD (95% CI) = -1.03 (-1.85, -0.22), p = 0.024) and changed from baseline (pooled SMD (95% CI) = -0.93 (-1.57, -0.28), p = 0.014). Omega-3 supplementation reduced the risk of CKD-aP (pooled RR (95% CI) = 0.68 (0.12, 3.81), p = 0.661). Omega-3 fatty acid supplementation appears to be a promising effective and safe treatment for CKD-aP. However, the included studies had several limitations that warrant further high-quality studies to elucidate its effect and investigate the causes of non-response in patients who did not improve.

2.
BMC Chem ; 18(1): 151, 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39135201

ABSTRACT

Tulathromycin (TUL) is a widely used veterinary antibiotic for treating bovine and porcine respiratory infections. Consuming animal-derived food contaminated with this medication may jeopardize human health. This work adopted the first portable potentiometric platform for direct TUL sensing in pharmaceutical and food products. The sensor employed a plasticized PVC membrane on a glassy carbon electrode doped with calix[6]arene and multi-walled carbon nanotubes (MWCNT) in a single solid contact layer for selective binding and signal stability. Characterization via scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) confirmed the material's integrity. The MWCNT-based sensor produced a stable Nernstian response (1.0 × 10-7 to 1.0 × 10-3 M) and a limit of detection (LOD) of 9.76 × 10-8 M with instantaneous response (8 ± 2 s). IUPAC validation revealed high selectivity for TUL against interfering ions, minimal drift (0.6 mV/h), and functionality over a broad pH range (2.0-7.0), allowing direct application to dosage form, spiked milk, and liver samples. Eco-Scale, AGREE, and Whiteness assessment proved the method's ecological sustainability, economic viability, and practical feasibility, surpassing traditional approaches.

3.
Int J Biol Macromol ; 278(Pt 1): 134688, 2024 Aug 11.
Article in English | MEDLINE | ID: mdl-39137856

ABSTRACT

CircRNAs have been increasingly appreciated as modulators of osteoporosis. This study investigated the expression of circ-0091579 and circ-HIPK3 in PBMCs of postmenopausal women with osteopenia and osteoporosis, aiming to underline their molecular mechanisms involved in pathogenesis of the disease. Seventy patients were stratified into two groups: 35 with osteopenia and 35 with osteoporosis, along with 30 healthy controls. Expressions of circ-0091579 and circ-HIPK3, miR-1225-5p and miR-338-3p, together with NF-κB, were assessed using RT-PCR. Keap1, Nrf2, and MAFB were determined using Western blot, while RANKL, OPG, IL-1ß, and IL-6 were measured by ELISA. GSH and MDA were estimated colorimetrically. Data revealed that circ-0091579 was markedly upregulated, whereas miR-1225-5p was downregulated in patients relative to controls. Additionally, circ-HIPK3 was significantly decreased, while miR-338-3p was increased in the diseased groups. Circ-0091579 was directly correlated with RANKL/OPG, NF-κB, IL-1ß, IL-6 and MDA, while inversely correlated with miR-1225-5p, T-score, BMD and GSH. Meanwhile, circ-HIPK3 and miR-338-3p were interrelated in an opposite manner. Eventually, the interplay among these downstream players induced an imbalance in bone homeostasis, triggering osteoporosis. Notably, these circRNAs differentiated patients from controls and those with osteopenia from osteoporotic ones. Thus, they could serve as biomarkers for early detection and tracking of osteoporosis.

4.
Spectrochim Acta A Mol Biomol Spectrosc ; 324: 125027, 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39197209

ABSTRACT

A green, simple and sensitive spectrofluorometric approach for determining vonoprazan fumarate in bulk and pharmaceutical dosage form by turning off the fluorescence of sodium salicylate is developed. The addition of vonoprazan fumarate reduced linearly the fluorescence intensity of 0.4 mM sodium salicylate at λem 408 nm and at λex 330 nm. The approach was found to be linear in the 50.0-3000.0 ng/mL range. The limits of detection and quantification were 10.97 and 33.23 ng/mL, respectively. The presented method proved its suitability in determination of vonoprazan fumarate in its pure and pharmaceutical dosage form. This method employs water as the exclusive solvent and utilizes safe reagents, evaluated using the Analytical Eco Scale, Green Analytical Procedure Index (GAPI), and carbon footprint. In contrast, previous methods relied on toxic reagents and required extended heating times, resulting in higher environmental impact. The novel method not only enhances analytical efficiency but also aligns with green chemistry principles, offering a sustainable solution for routine pharmaceutical analysis.

5.
Arts Health ; : 1-21, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39163557

ABSTRACT

BACKGROUND: There are a lack of studies examining the effect of creative art therapy on older people. This study aimed to evaluate the effect of creative art therapy on reducing depressive symptoms and improving the quality of life among Jordanian older people. METHODS: A one-group time-series design (pretest, posttest, and follow-up) was adopted between June 2021 and April 2022 on 102 community-dwelling older people who suffered from depressive symptoms and low quality of life in Amman Governorate. FINDINGS: Significant differences were found among older people in pre-, post-, and follow-up therapy for depressive symptoms and quality of life. Post hoc tests showed a statistically significant reduction in symptoms and an improvement in quality of life from pre to post-intervention, which was sustained at follow-up. CONCLUSION: Results suggested that using creative art therapies as a therapeutic intervention for older persons was effective in minimizing depressive symptoms and improving quality of life.

6.
Inflammopharmacology ; 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39192162

ABSTRACT

BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that lasts a long time and has a variety of causes. AIM: The primary aim of this study was to evaluate pentoxifylline's (PTX) essential function in patients with UC. METHODS: Fifty-two mild to moderate UC patients who matched the eligibility requirements participated in this clinical study. One gram of mesalamine (t.i.d.) and a placebo were administered to the mesalamine group (n = 26) for a duration of 24 weeks. Mesalamine 1 g t.i.d. and PTX 400 mg two times daily were administered to the PTX group (n = 26) for 24 weeks. A gastroenterologist investigated patients at the start and 6 months after the medication was given to assess disease activity index (DAI) and numeric pain rating scale (NRS). Also, interleukin-6 (IL-6), sphingosine 1 phosphate (S1P), tumor necrosis factor-alpha (TNF-α), and fecal myeloperoxidase (MPO) were measured before and after therapy. Zonula occuldin-1 (ZO-1) and signal transducer and activator of transcription factor-3 (STAT-3) expression was assessed before and after therapy as well as histological assessment. Short Form 36 Health Survey (SF-36), was assessed for each patient before and after 6 months of treatment. RESULTS: The PTX group showed statistically lower levels of serum SIP, TNF-α, IL-6, faecal MPO, gene expression of STAT-3, and a significant increase of ZO-1 in comparison with the mesalamine group. DAI and NRS significantly decreased whereas SF-36 significantly increased in the PTX group. CONCLUSION: PTX could alleviate inflammation in patients with UC, so it might be promising adjunctive for patients with UC. TRIAL REGISTRATION IDENTIFIER: NCT05558761.

7.
Life Sci ; 354: 122966, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39147320

ABSTRACT

Aberrant activation of the NLRP3 inflammasome is recognized to induce a chronic inflammatory response in the liver, ultimately leading to hepatic fibrosis. HSP90 is suggested to regulate NLRP3 activation and its downstream signaling. This study is the first to explore the potential therapeutic role of pimitespib in mitigating liver fibrosis in rats. The results of the study revealed that pimitespib effectively suppressed hepatic inflammation and fibrogenesis by modulating HSP90's control over the NFκB/NLRP3/caspase-1 axis. In vitro experiments demonstrated that pimitespib reduced LDH levels and increased hepatocyte survival, whereas in vivo, it prolonged the survival of rats with hepatic fibrosis. Additionally, pimitespib exhibited improvements in the function and microscopic characteristics of rat livers. Pimitespib effectively inhibited NFκB, which serves as the priming signal for NLRP3 activation. Pimitespib's inhibitory effect on NLRP3, identified as an HSP90 client protein, plays a central role in the observed anti-fibrotic effect. The simultaneous inhibition of both priming and activation signals of NLRP3 by pimitespib led to a reduction in caspase-1 activity and subsequent suppression of the N-terminal fragment of gasdermin D, ultimately constraining hepatocyte pyroptotic cell death. These diverse effects were associated with a decrease in the transcription of inflammatory mediators IL-1ß, IL-18, and TNF-α, as well as the fibrogenic mediators TGF-ß, TIMP-1, PDGF-BB, and Col1a1. Moreover, pimitespib induced the expression of HSP70, which could further contribute to the repression of fibrosis development. In summary, our findings provide an evolutionary perspective on managing liver fibrosis, positioning pimitespib as a promising candidate for anti-inflammatory and antifibrotic therapy.


Subject(s)
Caspase 1 , HSP90 Heat-Shock Proteins , Liver Cirrhosis , NF-kappa B , NLR Family, Pyrin Domain-Containing 3 Protein , Animals , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Rats , Liver Cirrhosis/metabolism , Liver Cirrhosis/pathology , Liver Cirrhosis/drug therapy , HSP90 Heat-Shock Proteins/metabolism , NF-kappa B/metabolism , Male , Caspase 1/metabolism , Signal Transduction , Rats, Sprague-Dawley , Inflammasomes/metabolism , Sulfonamides/pharmacology , Hepatocytes/metabolism , Hepatocytes/pathology , Hepatocytes/drug effects
8.
J Parasit Dis ; 48(3): 551-569, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39145357

ABSTRACT

Schistosomiasis is a neglected tropical disease with considerable morbidity. The lone effective drug, praziquantel (PZQ), is showing emergence of drug resistance hence, searching for new supportive treatment is crucial. This study aimed to evaluate the efficacy of mucus and nucleoproteins (NPs) extracted from Biomphalaria alexandrina (B. alexandrina) snails on miracidia, cercariae and Schistosoma mansoni (S. mansoni) adults in vitro and assess their experimental in vivo effect through parasitological, histopathological, and biochemical parameters. The in vivo study included 90 male Swiss albino mice. Mice were grouped into 9 groups; G1-G5 were infected and treated with; GI: PZQ, GII: mucus, GIII: combined PZQ and mucus, GIV: NPs, GV: combined PZQ and NPs. Control groups; C1: Non infected non treated (negative control), C2: Infected non treated (positive control), C3: Non infected mucus treated and C4: Non infected NPs treated. The in vitro study proved that the mucus had a better lethal effect on cercariae than miracidia, while NPs had better lethal effect on miracidia. The mucus lethal effect on adults surpassed the NPs as 100% and 60%, respectively. The in vivo study proved that the combined NPs or mucus with PZQ added to the effect of individual PZQ resulting in 100% total worm burden (TWB) reduction. As regard oxidative stress markers, the lowest level of nitric oxide (NO) was shown with combined PZQ and NPs. While, the highest glutathione (GSH) level was produced by individual PZQ. The study concluded that mucus and NPs of B. alexandrina had cercaricidal, miracidicidal and anti-schistosomal effect in vitro and that their combination could be considered a contribution to PZQ potentiality in vivo.

9.
Nucleic Acids Res ; 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39149883

ABSTRACT

Acinetobacter baumannii is an opportunistic Gram-negative pathogen that infects critically ill patients. The emergence of antimicrobial resistant A. baumannii has exacerbated the need to characterize environmental adaptation, antibiotic resistance and pathogenicity and their genetic regulators to inform intervention strategies. Critical to adaptation to changing environments in bacteria are small regulatory RNAs (sRNAs), however, the role that sRNAs play in the biology of A. baumannii is poorly understood. To assess the regulatory function of sRNAs and to uncover their RNA interaction partners, we employed an RNA proximity ligation and sequencing method (Hi-GRIL-seq) in three different environmental conditions. Forty sRNAs were ligated to sRNA-RNA chimeric sequencing reads, suggesting that sRNA-mediated gene regulation is pervasive in A. baumannii. In-depth characterization uncovered the sRNA Aar to be a post-transcriptional regulator of four mRNA targets including the transcript encoding outer membrane protein CarO. Aar initiates base-pairing with these mRNAs using a conserved seed region of nine nucleotides, sequestering the ribosome binding sites and inhibiting translation. Aar is differentially expressed in multiple stress conditions suggesting a role in fine-tuning translation of the Aar-target molecules. Our study provides mechanistic insights into sRNA-mediated gene regulation in A. baumannii and represents a valuable resource for future RNA-centric research endeavours.

10.
Sci Rep ; 14(1): 20008, 2024 08 28.
Article in English | MEDLINE | ID: mdl-39198544

ABSTRACT

Silver nanoparticles were successfully incorporated into a melamine-based polymer, resulting in the synthesis of (Ag NPs@Bipy-PAN) through a reverse double solvent approach. The synthesised Ag NPs@Bipy-PAN polymer underwent extensive characterisation through Powder X-ray Diffraction (PXRD), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy and Energy Dispersive X-ray (EDX) and Thermal Gravimetric Analysis. PXRD analysis confirmed the successful encapsulation of Ag nanoparticles and provided insights into the amorphous nature of the polymer following encapsulation. SEM and EDX analyses further corroborated the presence and distribution of Ag nanoparticles on the polymer surface. The biological efficacy of the Ag NPs@Bipy-PAN polymer was evaluated through antibacterial, anti-breast cancer, and biocompatibility assays. The results demonstrated notable antibacterial and anticancer activities, with significant efficacy against bacterial strains and breast cancer cells. Biocompatibility assessments indicated acceptable compatibility, particularly at a concentration of 2.5 mg/mL, compared to untreated control cells. These findings suggest that Ag NPs@Bipy-PAN has considerable potential as a candidate for cancer-targeted and antimicrobial drug delivery systems. The incorporation of silver nanoparticles into the melamine-based polymer enhances the safety profile of these systems in in vivo conditions, making them a viable option for advanced therapeutic applications.


Subject(s)
Anti-Bacterial Agents , Antineoplastic Agents , Metal Nanoparticles , Silver , Triazines , Silver/chemistry , Silver/pharmacology , Triazines/chemistry , Triazines/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Metal Nanoparticles/chemistry , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Microbial Sensitivity Tests , MCF-7 Cells , Female , Polymers/chemistry , Cell Line, Tumor , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , X-Ray Diffraction
11.
Pharmaceuticals (Basel) ; 17(8)2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39204107

ABSTRACT

A cost-effective, selective, sensitive, and operational TLC-densitometric approach has been adapted for the concurrent assay of Hydroxyzine Hydrochloride (HYX), Ephedrine Hydrochloride (EPH), and Theophylline (THP) in their pure powder and pharmaceutical forms. In the innovative TLC-densitometric approach, HYX, EPH, and THP were efficaciously separated and quantified on a 60F254 silica gel stationary phase with chloroform-ammonium acetate buffer (9.5:0.5, v/v) adjusted to pH 6.5 using ammonia solution as a mobile liquid system and UV detection at 220 nm. The novel TLC method validation has been performed in line with the international conference for harmonization (ICH) standards and has been effectively used for the estimation of the researched medicines in their pharmaceutical formulations without intervention from excipients. Additionally, parameters affecting the chromatographic analysis have been investigated. The new TLC approach's functionality and greenness were appraised using three modern and automated tools, namely the Blue Applicability Grade Index (BAGI), the Analytical Greenness metric (AGREE), and the Green Analytical Procedure Index (GAPI) tools. In short, the greenness characteristics were not achieved as a result of using mandatory, non-ecofriendly solvents such as ammonia and chloroform. On the contrary, the applicability and usefulness of the novel TLC approach were attained via concurrent estimation for the three drugs using simple and straightforward procedures. Moreover, the novel TLC method outperforms previously published HPLC ones in terms of the short run time per sample and moderate pH value for the liquid system. According to the conclusions of comparisons with previously recorded TLC methods, our novel HPTLC method has the highest AGREE score, so it is the greenest HPTLC strategy. Moreover, its functionality and applicability are very appropriate because of the simultaneous assessment of three drugs in one TLC run. Furthermore, no tedious and complicated extraction and evaporation processes are prerequisites.

12.
Eur J Med Chem ; 277: 116704, 2024 Nov 05.
Article in English | MEDLINE | ID: mdl-39121741

ABSTRACT

Since 2020, many compounds have been investigated for their potential use in the treatment of SARS-CoV-2 infection. Among these agents, a huge number of natural products and FDA-approved drugs have been evaluated as potential therapeutics for SARS-CoV-2 using virtual screening and docking studies. However, the identification of the molecular targets involved in viral replication led to the development of rationally designed anti-SARS-CoV-2 agents. Among these targets, the main protease (Mpro) is one of the key enzymes needed in the replication of the virus. The data gleaned from the crystal structures of SARS-CoV-2 Mpro complexes with small-molecule covalent inhibitors has been used in the design and discovery of many highly potent and broad-spectrum Mpro inhibitors. The current review focuses mainly on the covalent type of SARS-CoV-2 Mpro inhibitors. The design, chemistry, and classification of these inhibitors were also in focus. The biological activity of these inhibitors, including their inhibitory activities against Mpro, their antiviral activities, and the SAR studies, were discussed. The review also describes the potential mechanism of the interaction between these inhibitors and the catalytic Cys145 residue in Mpro. Moreover, the binding modes and key binding interactions of these covalent inhibitors were also illustrated. The covalent inhibitors discussed in this review were of diverse chemical nature and origin. Their antiviral activity was mediated mainly by the inhibition of SARS-CoV-2 Mpro, with IC50 values in the micromolar to the nanomolar range. Many of these inhibitors exhibited broad-spectrum inhibitory activity against the Mpro enzymes of other coronaviruses (SARS-CoV-1 and MERS-CoV). The dual inhibition of the Mpro and PLpro enzymes of SARS-CoV-2 could also provide higher therapeutic benefits than Mpro inhibition. Despite the approval of nirmatrelvir by the FDA, many mutations in the Mpro enzyme of SARS-CoV-2 have been reported. Although some of these mutations did not affect the potency of nirmatrelvir, there is an urgent need to develop a second generation of Mpro inhibitors. We hope that the data summarized in this review could help researchers in the design of a new potent generation of SARS-CoV-2 Mpro inhibitors.


Subject(s)
Antiviral Agents , Coronavirus 3C Proteases , Drug Design , SARS-CoV-2 , SARS-CoV-2/drug effects , SARS-CoV-2/enzymology , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Humans , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus 3C Proteases/metabolism , Structure-Activity Relationship , Protease Inhibitors/pharmacology , Protease Inhibitors/chemistry , Protease Inhibitors/metabolism , Small Molecule Libraries/chemistry , Small Molecule Libraries/pharmacology , COVID-19 Drug Treatment
13.
Medicine (Baltimore) ; 103(33): e39383, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39151509

ABSTRACT

The prevalence of anemia in adults with diabetes is of growing importance due to its impact on overall health and the management of diabetes-related complications. This study aimed to determine the prevalence of anemia among adult patients with diabetes at King Abdulaziz University Hospital in Jeddah, Saudi Arabia. A retrospective study was done on 1208 patients with diabetes >18 years who attended the study setting from 2010 to 2022. Data about patients' demographics, body mass index, glycated hemoglobin (HbA1c; %), hemoglobin (Hb), serum ferritin, iron, mean corpuscular Hb, mean corpuscular volume, free thyroxine and triiodothyronine (T3), and serum thyroid-stimulating hormone (TSH) were collected. Of patients, 86.6% had anemia with a prevalence of 30.2%, 47.6%, and 22.2% for mild, moderate, and severe anemias, respectively. The prevalence of anemia was significantly higher among females, those with high serum ferritin, normal serum iron or normal serum T3, lower mean HbA1c level (%), lower serum iron or T3, and higher serum ferritin or TSH. A significant positive correlation was found between Hb level and HbA1c level (%), serum iron, free T3, and body mass index. A significant negative correlation was found between Hb level and mean corpuscular volume, serum ferritin, and serum TSH. Being female, having high serum ferritin, lower mean free T3, and a high TSH were risk factors for anemia. The prevalence of severe anemia was significantly higher among patients with uncontrolled diabetes mellitus. A high prevalence of anemia was found among studied diabetics. Anemia screening should be included in the routine assessment of patients with diabetes. A multidisciplinary approach involving endocrinologists, hematologists, and dietitians is recommended to ensure holistic care and address all aspects of the patient's health. In addition, further research should be supported to better understand the mechanisms linking diabetes and anemia and to establish evidence-based guidelines for managing anemia in diabetics.


Subject(s)
Anemia , Ferritins , Glycated Hemoglobin , Hospitals, University , Humans , Female , Male , Retrospective Studies , Middle Aged , Anemia/epidemiology , Anemia/blood , Anemia/etiology , Adult , Saudi Arabia/epidemiology , Glycated Hemoglobin/analysis , Prevalence , Ferritins/blood , Aged , Body Mass Index , Diabetes Mellitus/epidemiology , Diabetes Mellitus/blood , Iron/blood , Thyrotropin/blood , Hemoglobins/analysis
14.
J Family Med Prim Care ; 13(5): 1962-1967, 2024 May.
Article in English | MEDLINE | ID: mdl-38948625

ABSTRACT

Background: Following the World Health Organization statement 'Health for all', family medicine is a specialty that provides continuing, comprehensive healthcare to individuals and their families. Despite that, it is still not yet utilized to its full potential by the developing Middle-Eastern community. The aim of our study is to assess the perception and utilization of family medicine services among Abu Dhabi Island's community. Methods: A cross-sectional study was conducted targeting Abu Dhabi Island's community. A representative sample with 95% confidence level and 5% margin of error was calculated taking into consideration the latest report by the Abu Dhabi Statistics Center. A total of 395 adult participants were included in the study, who were asked to fill in an electronic-based validated questionnaire. SPSS software was then used for data analysis. Results: Majority of participants were UAE nationals (81%) and married (71.1%), with almost equal male (50.4%) to female ratio (49.6%). Participants had positive experiences in primary healthcare (PHC) overall, regardless of their gender, nationality and marital status. Positive experience percentages dropped with higher age and educational level (P-value <0.05). A better understanding was noticed among ≥50 years of age with the rightful destination for emergency symptoms (P-value <0.05). Participants overall agreed on PHC being the preferred allocation for treatment of fever, body aches and sore throat. Conclusion: Primary healthcare centres were chosen as preferred destinations for emergency and non-emergency cases, as the vast majority had positive experiences when attending them.

15.
Fundam Clin Pharmacol ; : e13027, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38978462

ABSTRACT

BACKGROUND: Torsion of the spermatic cord is a hazardous and common urologic issue. The current work evaluates the possible protective effect of pregabalin (PGB) and xanthenone (XAN) in testicular ischemia/reperfusion injury induced by testicular torsion/detorsion in rats. MATERIALS AND METHODS: Seven groups of adult male Wistar albino rats were allocated randomly into seven groups, namely, sham control, torsion/detorsion (T/D), PGB 50 mg/kg, PGB 100 mg/kg, XAN 1 mg/kg, XAN 2 mg/kg, and PGB 50 mg/kg plus XAN 1 mg/kg groups. Serum cholesterol and testosterone levels were determined. Also, the levels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-қB), angiotensin (Ang) II, Ang-(1-7), and angiotensin-converting enzyme2 (ACE2) were assessed in testicular tissue. Immunohistochemical analysis of heme oxygenase-1 (HO-1) and caspase-3 was performed. Finally, the histopathological examination of the testicular tissues was performed. RESULTS: The PGB 50 mg/kg, PGB 100 mg/kg, XAN 1 mg/kg, XAN 2 mg/kg, and PGB 50 mg/kg plus XAN 1 mg/kg groups showed a significant decrease in serum cholesterol, MDA, NO, TNF-α, NF-қB, and Ang-II levels coupled with a significant increase in both testosterone and ACE2 expression. Furthermore, all test groups showed a significant improvement in the histopathological picture with a reduction in caspase-3 and an increase in HO-1 immunoexpression in testicular tissue. CONCLUSION: PGB and XAN may have promising effects on preventing testicular T/D injury through antioxidant, anti-inflammatory, and antiapoptotic actions.

16.
Molecules ; 29(14)2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39064972

ABSTRACT

Nanoscale geranium waste (GW) and magnesium nanoparticle/GW nanocomposites (Mg NP/GW) were prepared using green synthesis. The Mg NP/GW samples were subjected to characterization using X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR-FT). The surface morphology of the materials was examined using a scanning electron microscope (SEM), and their thermal stability was assessed through thermal gravimetric analysis (TG). The BET-specific surface area, pore volume, and pore size distribution of the prepared materials were determined using the N2 adsorption-desorption method. Additionally, the particle size and zeta potentials of the materials were also measured. The influence of the prepared nanomaterials on seed germination was intensively investigated. The results revealed an increase in seed germination percent at low concentrations of Mg NP/GWs. Upon treatment with Mg NP/GW nanoparticles, a reduction in the mitotic index (MI) was observed, indicating a decrease in cell division. Additionally, an increase in chromosomal abnormalities was detected. The efficacy of GW and Mg NP/GW nanoparticles as new elicitors was evaluated by studying their impact on the expression levels of the farnesyl diphosphate synthase (FPPS1) and geranylgeranyl pyrophosphate (GPPS1) genes. These genes play a crucial role in the terpenoid biosynthesis pathway in Sinapis alba (S. alba) and Pelargonium graveolens (P. graveolens) plants. The expression levels were analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. The qRT-PCR analysis of FPPS and GPPS gene expression was performed. The outputs of FPPS1 gene expression demonstrated high levels of mRNA in both S. alba and P. graveolens with fold changes of 25.24 and 21.68, respectively. In contrast, the minimum expression levels were observed for the GPPS1 gene, with fold changes of 11.28 and 6.48 in S. alba and P. graveolens, respectively. Thus, this study offers the employment of medicinal plants as an alternative to fertilizer usage resulting in promoting environmental preservation, optimal waste utilization, reducing water consumption, and cost reduction.


Subject(s)
Gene Expression Regulation, Plant , Pelargonium , Sinapis , Sinapis/genetics , Sinapis/drug effects , Sinapis/growth & development , Pelargonium/genetics , Pelargonium/growth & development , Gene Expression Regulation, Plant/drug effects , Nanoparticles/chemistry , Green Chemistry Technology , Germination/drug effects , Metal Nanoparticles/chemistry , Plant Proteins/genetics , Plant Proteins/metabolism , Spectroscopy, Fourier Transform Infrared
17.
Toxics ; 12(7)2024 Jun 21.
Article in English | MEDLINE | ID: mdl-39058097

ABSTRACT

Imidacloprid (IMI) is a commonly used new-generation pesticide that has numerous harmful effects on non-targeted organisms, including animals. This study analysed both the adverse effects on the pancreas following oral consumption of imidacloprid neonicotinoids (45 mg/kg daily for 30 days) and the potential protective effects of lycopene (LYC) administration (10 mg/kg/day for 30 days) with IMI exposure in male Sprague-Dawley rats. The apoptotic, pyroptotic, inflammatory, oxidative stress, and endoplasmic reticulum stress biomarkers were evaluated, along with the histopathological alterations. Upon IMI administration, noticeable changes were observed in pancreatic histopathology. Additionally, elevated oxidative/endoplasmic reticulum-associated stress biomarkers, inflammatory, pyroptotic, and apoptotic biomarkers were also observed following IMI administration. LYC effectively reversed these alterations by reducing oxidative stress markers (e.g., MDA) and enhancing antioxidant enzymes (SOD, CAT). It downregulated ER stress markers (IRE1α, XBP1, CHOP), decreased pro-inflammatory cytokines (TNF-α, IL-1ß), and suppressed pyroptotic (NLRP3, caspase-1) along with apoptotic markers (Bax, cleaved caspase-3). It also improved the histopathological and ultrastructure alterations brought on by IMI toxicity.

18.
Heliyon ; 10(12): e32714, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-39022102

ABSTRACT

This research describes the methodology for synthesizing zinc oxide nanoparticles (ZnO-NPs). It demonstrates a unique, cost-effective, and non-toxic chemical technique for producing ZnO-NPs using the precipitation method with NaOH as reducing and capping agents. The formed nanoparticles have been characterized and analyzed using numerous techniques such as; Fluorescence emission spectroscopy (FL), X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray Spectroscopy (EDX), ultraviolet-visible optical absorption (UV-Vis), Fourier transform infrared spectroscopy (FTIR), and Thermal gravimetric analysis (TGA). Also, the analytical technique X-ray diffraction studies has been used which showed that the ZnO-NPs had a Wurtzite hexagonal crystal structure with an average crystallite size of 34.27 nm. The form and the size of the synthesized ZnO-NPs have been seen in SEM and TEM photographs. Using J-image, particle size has been obtained at 13.33 nm, and the grain boundaries were all approximately spherical. Peaks in the FT-IR spectrum of the NPs indicate the presence of carboxylate (COO) and hydroxyl (O-H) functional groups. According to these findings, Zn interstitial defects are responsible for the 380 nm emission peak. Since EDX could not identify any impurities below the detection threshold, we may be sure that Zn and O are the principal components of the synthesized sample. ZnO-NPs cause an absorption band at 350.34 nm in the UV-Vis spectrum and a band gap of 3.24 eV. The catalytic activity of the synthesized ZnO nanoparticles (NPs) was evaluated by investigating their effectiveness in degrading crystal violet (CV) and methylene blue (MB) dyes, along with assessing the degradation rates. The results demonstrated a high degradation efficiency, with ZnO NPs achieving approximately 96.72 % degradation for CV and 97.169 % for MB dyes, underscoring their remarkable efficacy in the degradation process. As for antimicrobial activity assessment, the results revealed that the ZnO-NPs had negligible impact on Gram-negative bacteria, whereas they exhibited a discernible effect on Gram-positive bacteria. Additionally, it showed anti-cancer potential against colon (SW480), breast (MDA-231), and cervix (HELA) lines cells as seen by (MTT) assay. Hence, due to its simplified processes and cheaper chemicals, our synthesis technique may use in industrial settings for various applications.

19.
Bioorg Chem ; 151: 107680, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39084151

ABSTRACT

Breast cancer poses a significant health risk worldwide. However, the effectiveness of current chemotherapy is limited due to increasing drug resistance and side effects, making it crucial to develop new compounds with novel mechanism of action that can surpass these limitations. As a consequence of their reversible and targeted mechanism, DNA minor groove binders (MGBs) are considered as a relatively safer and more effective alternative. In this study, transcriptomic analysis was conducted to reveal the dysregulated genes and signaling pathways in MCF7 cancer cells following treatment with novel MGB ligands to gain insights into the mechanism of action of MGBs at the molecular level. The transcriptomic results were validated using real-time PCR. The findings of this study indicate that the investigated MGBs primarily inhibit the genes associated with the estrogen receptor. Remarkably, ligand 5 showed downregulation of 34 out of the 35 genes regulated by estrogen receptor, highlighting its potential as a promising candidate for breast cancer therapy.


Subject(s)
Breast Neoplasms , Receptors, Estrogen , Humans , MCF-7 Cells , Receptors, Estrogen/metabolism , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Female , Dose-Response Relationship, Drug , Molecular Structure , Structure-Activity Relationship , Drug Screening Assays, Antitumor , Transcriptome/drug effects , Cell Proliferation/drug effects , Gene Expression Profiling , Ligands , Tumor Cells, Cultured
20.
Int J Dent ; 2024: 1217448, 2024.
Article in English | MEDLINE | ID: mdl-38962725

ABSTRACT

Background: Several endodontic difficulty assessment forms are available to help dental students and general dentists estimate the difficulty of the case before initiating the endodontic treatment. Objectives: This study aimed to assess if the American Association of Endodontics (AAE) case difficulty assessment form affects the dental student's perception of the difficulty encountered while performing root canal treatment (RCT). Materials and Methods: This was a cross-sectional online survey. After obtaining IRB approval, an electronic questionnaire was sent to dental students enrolled in the 4th and 5th years at King Saud University (KSU) and King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia. The questionnaire was divided into informed consent, demographic data, the use of the AAE case assessment form, RCT steps, diagnosis, local anesthesia administration, tooth isolation, and endodontic procedure. Results: A total of 195 dental students participated in the study. There were 101 (52%) females, and 139 (71%) were from KSAU-HS. A positive association was found between students who used the AAE assessment form and who did not with their ability to reach the correct diagnosis (p=0.005), tooth isolation (p=0.03), and endodontic procedure difficulty score (p=0.018). Conclusion: The use of the AAE form by dental students enabled them to differentiate between complicated and uncomplicated cases, thus lowering the difficulty encountered during RCT.

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