Explore the vast range of titles available.

Hypoxemia brain injuries arise when the brain’s oxygen supply is restricted. Brain cells gradually die and become impaired as a result of the restricted oxygen flow a diversity of signaling pathways are involved in the pathophysiology of brain damage. One of the main concerns when examining the rate of protein breakdown is the measurement of the serum amino acid ratio. Valine, leucine, and isoleucine make up branched-chain amino acids, while phenylalanine and tyrosine make up aromatic amino acids. A vital tool for assessing the severity of hypoxemia is Fischer’s ratio. The goal of this article is to determine how quercetin (QUR) and/or mexamine (MEX) prevented synfat (SN)-induced brain damage in a rat models. It also aimed to elucidate the various cross-linked inflammatory pathways, DNA damage, and Fischer’s ratio. Following QUR and MEX therapy, synfat-induced hypoxemia. Hemoglobin (Hb) levels were markedly reduced by synfat-intoxication, and oxidative stress and inflammatory biomarkers, including TNF-??, MDA, interleukin-6 (IL-6), and C -reactive protein (CRP), were elevated. Hemoglobin levels, oxidative stress biomarkers, and the aberrant expression of pro-inflammatory cytokines were all altered by QUR and/or MEX therapy. Similarly, the concentration of γ-aminobutyric acid, serotonine, noradrenaline, and intropin in cerebral tissue is restricted. Similarly, the COMET assay and 8-oxo-7,8-dihydro-2’-deoxyguanosine analysis (8-oxodG) demonstrated that QUR and MEX potentially altered synfat-induced brain DNA damage. The results confirmed the potential impact of this combined strategy as a powerful therapy for brain hypoxemia, concluding that treatment via QUR with MEX was superior therapy in modulating synfat-triggered cerebral injury.

CRISPR/Cas9 is a recently discovered genomic editing technique that altered scientist’s sight in studying genes function. Cas9 is controlled via guide (g) RNAs, which match the DNA targeted in cleavage to modify the respective gene. The development in prostate cancer (PC) modeling directed not only to novel resources for recognizing the signaling pathways overriding prostate cell carcinoma, but it has also created a vast reservoir for complementary tools to examine therapies counteracting this type of cancer. Various cultured somatic rat models for prostate cancer have been developed that nearly mimic human prostate cancer. Nano-medicine can passively target cancer cells via increasing bioavailability and conjugation via specific legend, contributing to reduced systemic side-effects and increased efficacy. This article highlights liposomal loaded Nano-medicine as a potential treatment for prostate cancer and clarifies the CRISPR/Cas9 variation accompanied with prostate cancer. PC is induced experimentally in western rat model via ethinyl estradiol for 4 weeks and SC. dose of 3, 2’- dimethyl-4-aminobiphenyl estradiol (DAE) (50mg/kg) followed by treatment via targeted liposomal-coated compounds such as liposomal dexamethasone (DXM), liposomal doxorubicin (DOX) and liposomal Turmeric (TUR) (3mg/kg IP) for four weeks in a comparative study to their non-targeted analogue dexamethasone, doxorubicin and Turmeric. 3, 2’- dimethyl-4-aminobiphenylestradiol elicit prostate cancer in western rats within 5 months. Simultaneous supplementations with these liposomal compounds influence on prostate cancer; tumor markers were investigated via prostate-specific antigen (PSA), Nitric oxide (NOX) and CRISPR/Cas9 gene editing. Several long non-coding RNAs were reported to be deregulated in prostate cell carcinoma, including MALAT1 . On the other hand, gene expression of apoptotic biomarkers focal adhesion kinase (AKT-1), phosphatidylinistol kinase (PI3K) and glycogen synthase kinase-3 (GSK-3) was also investigated and further confirming these results via histopathological examination. Liposomal loaded dexamethasone; doxorubicin and Turmeric can be considered as promising therapeutic agents for prostate cancer via modulating CRISPR/Cas9 gene editing and long non coding gene MALAT1 .

BackgroundResveratrol (RVS) is a stilbene derivative polyphenolic compound extensively recognized for its anti-inflammatory, antioxidant and anti-aging properties, along with its enormous promise in carcinoma treatment. Unfortunately, the oral supplementation of RVS possesses physicochemical and pharmacokinetic constraints that hinder its effects, necessitating the development of suitable administration strategies to improve its effectiveness. As a result, the current study evaluates the use of resveratrol nano-formulations in ovarian cancer therapy. Ovarian cancer was induced in rats using (35 mg/kg BW) 20-Methyl cholanthrene (20-MC) followed by resveratrol and resveratrol nano-formulations therapy for one month.Results20-MC highlighted a noticeable alleviation in autophagy (ATF) biomarkers SIRT-1 and Beclin, inflammatory and apoptotic biomarkers MMP-9, P53 and AKT in addition to oxidative and nitrosative stress biomarkers TAC and NOX and ovarian cancer tumor biomarker CA-125.ConclusionsResveratrol and resveratrol nano-formulations modulated autophagy, inflammatory and oxidative stress biomarkers with the upper effect for resveratrol nano-formulations in competing 20-MC-induced ovarian cancer.

Endometrial cancer (EC) is the fourth most abundant gynecological cancer. There is an increase in the incidence of mortality from uterine cancers in the past few decades. A comprehensive systematic study to provide an overview on the relationship between autophagy, metabolomics and the risk of oestradiol valerate (OV) induced endometrial cancer was conducted correlated with the use of liposomal loaded-resvida as an innovate drug delivery system. This article explores how metabolomic technology can offer valuable insights on autophagy molecular aspects in EC by identifying new possible metabolite biomarkers that has the potential to improve the accuracy of diagnosis, prognosis and disease monitoring. Metabolomics approach, included orthogonal partial least squares discriminant analysis (OPLS-DA), thus revolutionizes the management of endometrial cancer. Autophagy described in endometrial cancer, includes the role of HSP-70/C-fos/PTEN/mTOR/ERDj-4/p53 signaling pathways that trigger/inhibit the process and consequently represent a potential molecular targets in therapeutic approaches. Endometrial cancer exhibits a molecular complexity and heterogeneity coherent with histopathologic and metabolomic variability. Multivariate statistical analyses pointed out a noteworthy deviation in serum chemical profiles among control, oestradiol valerate, and Resvida and liposomal-Resvida treated groups. Loading plot guided the selection of differential metabolites, elucidating significant variation in metabolite concentration. Improved characterization of molecular alterations of each histological type provides relevant information about the prognosis and potential response to new liposomal therapies. CA125 as EC biomarker was ameliorated post Resvida (108.7 IU/mL) and liposomal Resvida (82.2 IU/Ml) treatment at P ≤ 0.05 in addition to up regulating autophagy biomarkers including mTOR/Cfos/ERDj-4/ PTEN by 20, 25, 14, and 17 fold change respectively and down regulating p53 protein expression by 0.4 ng/ml at P ≤ 0.05 post OV intoxication with liposomal regimen reflecting the most significant impact in modulating these altered genes. The current metabolomics study is the integration of histopathologic and autophagy molecular factors to improve the diagnosis, prognosis, and treatment of endometrial cancer in coherent with liposomal drug delivery system as a targeted therapy.

Micro-RNAs (mi-RNAs) can regulate various tumor suppressor genes or oncogenes thus they were monitored in various types of cell carcinoma. Lung cancer extensive progress has led not only to understanding the molecular pathways governing human lung cancer, but it has also created a vast reservoir for alternative development of novel liposomal Nano-medicines counteracting this malignancy. Liposomal drug delivery system can passively accrue in cancer cells via the retention phenomenon and enhanced permeability. This article highlighted liposomal-loaded nano-medicine as a potential treatment for lung cancer and clarifies the correlated miRNA and mRNA gene profile. Lung cancer was induced experimentally in rats via 3-methylcholanthrene (3-MCA) in a dose of 40 mg IV for 4 months followed by treatment via certain liposomal-loaded compounds, namely, liposomal doxorubicin (LIP-DOX), curcumin (LIP-CUR) and glutathione (LIP-GSH) in a dose of 5mg/kg IP daily for 1 month and were compared with their non-liposomal analogue. Concomitant supplementation with the aforementioned liposomal-loaded compounds impact on lung cancer was estimated via monitoring microRNA biomarkers including miR-122-5P and SNORD-78, pro-inflammatory biomarker Survivin, apoptotic and cell survival biomarkers including fms-related tyrosine kinase 3 (FLT-3), jasnus Janus kinase-2 (JAK-2), Phosphatidylinositol-3-kinase (PI3K), serine–threonine protein kinase (AKT) and tumor suppressor protein (P53). Liposomal-loaded doxorubicin, curcumin and glutathione significantly modulated these previously deviated genes as compared with their non-liposomal analogue, in addition to modulating lipid peroxide (LPOO) and total antioxidant capacity (TAC). MiR-122-5P and SNORD-78 were also amended reflecting the prospective impact of liposomal-loaded-nano-medicine on lung cancer treatment via up regulating P53 and down regulating PI3K/AKT/JAK2/FLT3 signaling pathway.

Methotrexate (MX), a competitive inhibitor of dihydrofolate reductase, can inhibit DNA and RNA production and is a powerful anticancer agent widely utilized in clinical practice for treating nonneoplastic maladies, as psoriasis and rheumatoid arthritis; meanwhile, its probable prescription dose and interval of administration are strictly limited due to dose-related organ damage. Former studies verified that kidney, brain, liver, and lung harms are prospective obstacles of methotrexate administration. To understand the machinery of methotrexate-prompt toxicity, various mechanisms were investigated. The former is an autophagy defense mechanism; autophagy is a self-digesting mechanism responsible for the removal of damaged organelles and malformed proteins by lysosome. The contemporary article hypothesized that turmeric or its liposomal analog could defeat autophagy of MX-induced acute toxicity. Methotrexate, in a dose of 1.5 mg/kg, was administered intravenously followed by turmeric and liposomal turmeric treatment in a dose of 5 mg/kg for 30 days in rats. Increment in autophagy (AUTP) consent by MX administration was attenuated by concurrent treatment via turmeric and liposomal turmeric that was reliable on the alteration in apoptotic markers. The assembly of FOXO-3 in serum post methotrexate administration was suppressed by concurrent treatment via liposomal turmeric. Apoptosis/autophagic marker investigation was evaluated through the gene expression of Bax (BCL2-associated X protein)/Bcl2 (B-cell lymphoma 2)/P53 (tumor protein P53)/SiRT-1 (sirtuin silent mating-type information regulation 2 homolog 1) and FOXO-3 (forkhead box transcription factor-3)/ERDJ-4 (endoplasmic reticulum localized DnaJ homologs)/BNP (brain natriuretic peptide B) signaling. The cell death of all cells was categorized to achieve autophagy. Interestingly, Bax/Bcl2/P53/SiRT-1 signaling pathways were downregulated, contributing to inhibiting the initiation of autophagy. Meanwhile, FOXO-3/BNP/ERDJ-4 reduction-implicated noncanonical autophagy pathways were involved in methotrexate-induced autophagy, whereas this change was suppressed when turmeric was administered in liposomal form. These outcomes recommended that liposomal turmeric prevents MX-induced acute toxicity through its autophagy, antioxidant, and antiapoptotic properties.

Background Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder with significant metabolic and hormonal dysregulation. Marjoram ( Origanum majorana L.), known for its medicinal properties, has potential in managing PCOS through various bioactive compounds. Objective This study aims to evaluate the effects of marjoram on PCOS symptoms using serum pharmacochemistry, network pharmacology, and molecular docking in a DHEA-induced rat model. Methods Polycystic Ovary Syndrome (PCOS) was induced in rats using dehydroepiandrosterone (DHEA). Marjoram’s therapeutic effects were evaluated by analyzing oxidative stress biomarkers, hormone levels, and ovarian histopathology. Untargeted serum metabolomics, conducted with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC TQD-MS/MS), identified key bioactive compounds. These compounds were then examined through network pharmacology to map their interactions with PCOS-related pathways, with findings validated via molecular docking. Results Marjoram treatment significantly reduced oxidative stress by decreasing nitric oxide (NO) and increasing total antioxidant capacity (TAC). Hormonal analysis revealed that high-dose marjoram (100 mg/kg) normalized progesterone, estradiol, testosterone and FSH levels. Body weight gain was also reduced with marjoram treatment, especially at the higher dose. Histopathological evaluation showed fewer ovarian cysts and improved follicular structure with marjoram administration. Network pharmacology analysis highlighted the steroid hormone biosynthesis and estrogen signaling pathways as critical targets, with apigenin and oleic acid identified as active compounds. Molecular docking confirmed strong interactions of these compounds with core PCOS-associated proteins, further supporting marjoram’s potential in modulating PCOS symptoms. Conclusion This study reveals that marjoram contains a diverse range of active compounds that can modulate crucial biochemical and histological markers related to PCOS. By combining serum pharmacochemistry with network pharmacology, the research highlights marjoram’s potential as a natural supplement to help alleviate PCOS symptoms and slow the syndrome’s progression. These findings support further investigation into marjoram’s role as a complementary therapy for managing PCOS.

Aluminum chloride (AlCl3) is commonly used in daily life; meanwhile, it is the potential etiology of various neurodegenerative as well as hepatorenal diseases. Therefore, the present study was carried out to investigate the correlation between AlCl3-induced biochemical alterations and the toxicity induced in various organs such as the brain, liver, and kidney. Male mice received AlCl3 in an oral dose of 50 mg kg−1 in addition to (50 mg) in drinking water for 2 weeks. Two weeks post-AlCl3 intoxication, the brain, liver, and kidney biochemical indices were assessed via molecular and western blot analysis. The results are as follows: AlCl3 intoxication induced a significant elevation in serum malondialdehyde in addition to a significant reduction in serum glutathione (GSH) and superoxide dismutase (SOD) levels. Brain β-secretase (tubulin-binding protein) and tau proteins which are responsible for the synthesis of β-amyloid protein that may interfere with neuronal communication in Alzheimer’s disease (AD) were also upregulated; regarding hepatic function, AlCl3 elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Moreover, it upregulated hepatic mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) protein expressions as well as renal kidney-inducible molecule-1 (KIM-1) which indicated the deleterious effect of AlCl3 on these organs. These results were confirmed by histopathological investigations. So, we hypothesize that acute AlCl3 administration is responsible for oxidative cell damage that interferes with brain function inducing β-amyloid accumulation, Alzheimer’s disease, and neurodegenerative damage as well as hepatorenal injuries.

Background and ObjectivesNanoparticle (NP) drug delivery systems have been developed recently to resolve the obstacle of drug resistance, contributing to the effective drug delivery to the target organ. A comparative study was carried out herein between doxorubicin (DOX), doxorubicin-loaded titanium NPs, DOX-loaded lactoferrin NPs, DOX-NPs, and PEGylated-doxorubicin (PEG-DOX) on the reno-carcinogenic impact of 3-methylcholanthrene (CA).MethodsIn-vivo models were exposed to CA at a dose of 50 mg/kg body weight and left for 3 months till the incidence of chronic kidney disease, followed by one month of treatment with the aforementioned nanomedicines.ResultsCA downregulated DOX resistance biomarkers, including the gene expression of KRAS, FKBP5, P53, and JAK2, and the kidney tumor marker arginase II. In addition, CA increased the levels of the kidney biomarkers creatinine and urea as well as the minerals chloride and magnesium. Decreased gene expression of FKBP5, KRAS, P53, and JAK2 was reversed after the treatment with DOX-loaded titanium NPs, DOX-NPs, DOX-loaded lactoferrin NPs, and PEG-DOX. PEG-DOX abolished the detrimental effects of CA via upregulating the gene expression of the immunophilin protein (FKBP5), the oncogene (KRAS), the tumor suppressor gene (P53), and JAK2, which indicate DOX drug resistance via regulating cell differentiation, division and apoptosis.ConclusionPEG-DOX restored renal function and resolved DOX resistance via KRAS, FKBP5, P53, and JAK2 signaling pathways manipulation; consequently, PEG-DOX may provide a useful adjunct treatment for chronic kidney disease.

Background and objectiveBone marrow-derived mesenchymal stem cells (MSCs), possess the unique ability of self-renewal and development into specialized cells, and long-lived cells with specific metabolic needs. It has been demonstrated that autophagy is essential for MSC differentiation, quiescence, activation, and self-renewal. The present study aims to elucidate how autophagy influences bone marrow-derived MSC post-novodrin-prompted liver dysfunction.MethodsHepatic dysfunction was induced in rats using novodrin (100 mg/kg, subcutaneously), which was divided into two doses for two alternative days, followed by the treatment with 100 µL of intravenous injection of allogeneic MSCs (5 × 106).ResultsA month preceding MSC therapy, a marked decline in liver function biomarkers, including alanine aminotransferase and aspartate aminotransferase, was observed, in addition to the significant decrease in oxidative stress biomarker, lipid peroxide. Meanwhile, novodrin significantly elevated the gene expression of cell survival biomarkers, including signal transducer and activator of transcription, phosphatidylinositol-3-kinase, and serine/threonine kinase-1, in addition to the concomitant increase in oncogenic biomarker, phosphatase and tensin homolog, and this was reversed post-MSC implantation. Furthermore, the autophagy biomarkers, including Beclin-1 and X-box binding protein 1, were restored post-MSC implantation. Moreover, the MSCs labeled with the PKH26 red fluorescent dye were sown into the injured liver tissue, which presented with hepatic tissues with a nearly normal architecture as confirmed through histopathological examination.ConclusionThe present study demonstrated that autophagy is essential for bone marrow-derived MSC in novodrin-induced liver dysfunction.