ikooo, [22.04.25 10:31] Intestinal malignancy presents a worldwide health concern. 1 A significant hurdle in therapeutic intervention involves neoplastic resistance to pharmacological agents, a phenomenon often linked to imbalances within the redox regulatory framework. Zinc oxide nanostructures have demonstrated antineoplastic properties by perturbing this equilibrium. Biocompatible fabrication techniques have positioned ZnO    as a potentially advantageous strategy. The current investigation explores the influence of zinc oxide nanoparticles, generated via both conventional chemical routes and environmentally friendly biogenic pathways, on crucial markers of cellular oxidation and the antioxidant defense network in HT-29 colorectal adenocarcinoma cells. These markers encompass malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH). The central objective is to contrast the impact of these nanostructures on the fluctuations of these indicators and to elucidate the contribution of these alterations to the initiation of programmed cell death within HT-29 cells. In this study, zinc oxide nanoparticles were produced using a sustainable biogenic approach employing pomegranate fruit rind extract. The active phytochemical constituents of the plant-derived material were characterized through gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC). The resulting nanostructures underwent comprehensive analysis utilizing X-ray diffraction (XRD), dynamic light scattering (DLS), ultraviolet-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), zeta potential measurements, and field-emission scanning electron microscopy (FE-SEM). 2 The findings substantiated the formation of nanostructures exhibiting a hexagonal wurtzite crystalline arrangement, nanoscale dimensions, and both spherical and hexagonal shapes. 3 Biogenically fabricated zinc oxide nanoparticles were evaluated in parallel with chemically synthesized counterparts on HT-29 cells. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay results indicated that the biogenic nanoparticles displayed more pronounced cytotoxic effects, with an inhibitory concentration 50% (IC50) value of 80.28 ?g/mL. Quantification of oxidative stress biomarkers and antioxidant molecules revealed an elevation in MDA levels coupled with a reduction in SOD and GSH concentrations in the group treated with the biogenic nanoparticles. Acridine orange/propidium iodide (AO/PI) and 4?,6-diamidino-2-phenylindole (DAPI) staining assays corroborated the induction of apoptosis in malignant cells exposed to the biogenic nanoparticles. Zinc oxide nanoparticles synthesized through an eco-friendly method utilizing pomegranate peel extract exhibit considerable promise in enhancing the treatment of colorectal cancer by disrupting the oxidant/antioxidant balance within cancerous cells

  

اين مطالعه به منظور درك هرچه بهتر ارتباط ميان يافته هاي باليني ، هيستوپاتولوژيك و بيان پروتئينهاي مرتبط با آپوپتوز(BCl-2,P53) در اندومتر سگهاي ارجاعي به كلينيكهاي سطح شهر كرمانشاه براي جراحي اوريوهيستركتومي طراحي شده است. مجموع 25 رحم خارج شده به روش جراحي انتخابي، از سگهاي ماده بين سنين 2 تا 12 سال، ابتدا مورد بررسي باليني و هيستوپاتولوژي از جهت وجود هيدرومتر، موكومتر، پايومتر و هيپرپلازي كيستي اندومترقرار گرفته و سپس ماركرهاي BCl-2و P53 با تكنيك ايمونوهيستوشيمي در بافت رحم لوكاليزه و رديابي ميشوند. از حيوانات انتخاب شده قبل از عمل جراحي نمونه خون گرفته شده و ميزان هورمونهاي استراديول ، پروژسترون و فاكتورهاي خوني حيوان ارزيابي ميشوند.

مقادير اندازه‌گيري شده در نمونه‌هاي پاتولوژيك همچنين با مقادير اندازه‌گيري شده در نمونه‌هاي سالم از لحاظ باليني، هيستولوژي بافت رحم، ايمونوهيستوشيمي ماركرهاي مذكور و پارامترهاي خوني 5 قلاده سگ كه مورد اواريوهيستركتومي انتخابي قرار مي‌گيرند مقايسه خواهند شد.

  

Colorectal cancer is one of the most significant health threats, with current treatments facing challenges such as severe side effects and cellular resistance. Inducing apoptosis has emerged as an innovative approach to overcoming these obstacles. Green-synthesized nanoparticles have shown great promise in this regard. These nanoparticles can effectively eliminate cancer cells by inducing apoptosis while minimizing side effects.

In this in vitro study, aimed at evaluating antitumor potential and apoptosis induction, zinc oxide nanoparticles (ZnO   ) were synthesized via a green method using ethanolic pomegranate peel extract (Punica granatum). Initially, bioactive compounds in the pomegranate peel extract were identified using gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC). The nanoparticles were subsequently characterized using techniques such as X-ray diffraction (XRD), dynamic light scattering (DLS), ultraviolet-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), and field-emission scanning electron microscopy (FE-SEM). The results confirmed the formation of ZnO nanoparticles with a hexagonal wurtzite crystal structure, nanoscale size, and spherical and hexagonal morphology.

The antitumor effects and apoptosis-inducing capabilities of green-synthesized ZnO    were compared with chemically synthesized ZnO    on colorectal cancer cells (HT-29). MTT assay results demonstrated that green-synthesized ZnO    exhibited stronger dose-dependent cytotoxic effects than their chemically synthesized counterparts. The IC50 value for green-synthesized nanoparticles was determined to be 80.28 µg/mL, indicating higher cytotoxicity compared to chemically synthesized ZnO   . Acridine orange/propidium iodide and DAPI staining techniques revealed a significant increase in apoptosis in cancer cells treated with green-synthesized ZnO   . Furthermore, immunocytochemistry (ICC) analysis showed a significant increase in p53 protein levels and a substantial decrease in Bcl-2 protein expression in these cells (p ? 0.0001).

These findings indicate that green-synthesized ZnO    exert stronger cytotoxic and apoptosis-inducing effects on cancer cells compared to chemically synthesized nanoparticles. The results of this study clearly demonstrate that green synthesis of ZnO    using pomegranate peel extract (P.G.) offers much higher potential for inducing cellular apoptosis and inhibiting tumor cell growth. These findings open new horizons in cancer nanotechnology, suggesting that green-synthesized ZnO    could serve as a promising therapeutic agent in cancer treatment.

Keywords: Apoptosis, BCL-2, p53, colorectal cancer cells HT-29, zinc oxide nanoparticles, green synthesis, immunocytochemistry (ICC).

Colorectal cancer (CRC) is one of the most prevalent and fatal types of cancer. Despite advances in therapeutic strategies, the limitations and side effects of current treatments underscore the urgent need for novel and more effective approaches. Among these, zinc oxide nanoparticles (ZnO   ) have emerged as a promising candidate for cancer therapy due to their significant antitumor properties and the feasibility of environmentally friendly synthesis methods. While numerous studies have explored the antitumor effects of ZnO   , the precise mechanisms of action and their relationship with alterations in tumor marker expressions, such as carcinoembryonic antigen (CEA) and Kirsten rat sarcoma viral oncogene homolog (KRAS), remain inadequately understood.

This study aims to elucidate the dual effects of green-synthesized ZnO    on HT-29 colorectal cancer cells and their impact on the expression of these tumor markers, contributing to the personalization of treatments and improvement of therapeutic outcomes for CRC patients. Additionally, to assess the role of synthesis methods in nanoparticle efficacy, the results of green-synthesized ZnO    were compared with those of chemically synthesized ZnO   .

Green synthesis of ZnO    was performed using ethanolic pomegranate peel extract (Punica granatum). Bioactive compounds in the extract were identified using gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC). The synthesized nanoparticles were characterized using X-ray diffraction (XRD), dynamic light scattering (DLS), ultraviolet-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), zeta potential analysis, and field-emission scanning electron microscopy (FE-SEM). The results confirmed the formation of nanoscale particles with a hexagonal wurtzite crystal structure, spherical and hexagonal morphology.

The antitumor effects of the green-synthesized ZnO   , compared to chemically synthesized ZnO   , were evaluated on colorectal cancer cells. The MTT assay revealed that green-synthesized ZnO    exhibited stronger dose-dependent cytotoxic effects on colorectal cancer cells than their chemically synthesized counterparts, with an IC50 value of 80.28 µg/mL. DAPI and acridine orange/ethidium bromide staining demonstrated significant tumor cell growth arrest in cancer cells treated with green-synthesized ZnO   . Furthermore, ELISA analysis showed a substantial reduction in tumor biomarkers CEA and KRAS.

The findings of this study suggest that integrating novel therapeutic approaches, including the application of green-synthesized ZnO    using ethanolic pomegranate peel extract (P.G.), along with precise evaluation of multiple tumor biomarkers, could lead to significant advancements in targeted and effective colorectal cancer therapies.

Keywords: Zinc oxide nanoparticles, green synthesis, colorectal cancer cells, HT-29, tumor biomarkers, ELISA, DAPI staining, acridine orange/ethidium bromide.

  

Cyclosporine is a widely used immunosuppressant drug that helps the body accept a tra  lanted organ by reducing the activity of T lymphocytes. However, it can cause toxicity in various organs, including the kidneys. Alpha-pinene is a cyclic monoterpene with strong antioxidant effects. So the current study aimed to investigate the potential protective effects of alpha-pinene on cyclosporine-induced nephrotoxicity. 35 male Wistar rats were divided into 5 equal groups (n = 7). They were subjected to oral treatment for 21 consecutive days as follows: negative control (normal saline), positive control (normal saline), comparative control (vitamin C: 100 mg/kg), and two experimental groups (alpha-pinene with doses of 50 and 100 mg/kg). Additionally, cyclosporine was administered intraperitoneally (25 mg/kg) for 21 days in all groups except the negative control. After the end of the treatment period, on the 22nd day, blood was taken from the heart of the animals under anesthesia, and then by deepening the anesthesia, the animals were euthanized and their kidneys were removed to investigate the histopathology and immunohistochemistry as well as oxidative stress indices evaluation. The results indicated that treatment with alpha-pinene led to a reduction in serum urea and creatinine levels, as well as an improvement in the histopathological lesions caused by cyclosporine. Also, the finding showed that alpha-pinene decreased the apoptotic process by lowering the p53 protein and increasing Bcl2. It also significantly inhibited the oxidative stress caused by cyclosporine in the kidney tissue by reducing the levels of malondialdehyde and increasing superoxide dismutase and total antioxidant capacity. This study demonstrated that treatment with alpha-pinene had a significant protective effect against cyclosporine-induced nephrotoxicity, comparable to that of vitamin C, possibly due to its antioxidant and anti-apoptotic properties.

مرغ مينا يكي از پرندگاني است كه به عنوان پرنده خانگي و زينتي نگهداري مي‌شود‌. با توجه به شرايط نگهداري و سيستم گوارشي –كبدي خود پرنده، بيماري كبد چرب و ذخيره آهن از شايع ترين بيماري ها در اين گونه از پرندگان است كه بيشترين علت ارجاع پرنده به كلينيك مي‌باشد. هدف مطالعه حاضر مقايسه نشانگرهاي كلينيكال پاتولوژي و راديولوژي با تأكيد بر نشانه هاي عارضه ليپيدوز كبدي و بيماري ذخيره آهن در مرغان مينا‌ (Acridotheres tristis) ارجاعي به كلينيك‌هاي دامپزشكي كرمانشاه مي‌باشد. در اين مطالعه از 30 مرغ ميناي ارجاعي به كلينيك هاي كرمانشاه، پس از گرفتن تاريخچه و معاينه، با اخذ رضايت كتبي از صاحب پرنده، خون‌گيري از وريد بال(Brachial vein)صورت خواهد گرفت، سرم خون پس از جداسازي براي بررسي و ارزيابي پارامترهاي بيوشيميايي همچون سنجش ميزان پروتئين كل، آلبومين،تريگليسيريد، آهن و آنزيم هاي كبدي در فريزر با دماي منفي 20 درجه سلسيوس نگهداري خواهد شد. همچنين براي ارزيابي پراكسيداسيون چربي در سرم، ميزان مالون‌دي‌آلدهيد سنجيده خواهد شد. از تمام پرنده‌ها عكس راديولوژي با حالت گماري در دو وضعيت شكمي پشتي و جانبي تهيه شده و مورد ارزيابي قرار خواهد گرفت. در صورت امكان آزمايش تكميلي بيوپسي كبدي انجام و با رنگ آميزي هماتوكسيلين-ائوزين، اسيد پريوديك شيفت و ماسون تري كروم انجام خواهد شد. داده هاي به دست آمده از نتايج آزمايش ها بصورت ميانگين و انحراف استاندارد بوده و با استفاده از آزمون t مورد ارزيابي قرار گرفته و همچنين براي بررسي ارتباط نتايج از ضريب همبستگي پيرسون استفاده خواهد شد.

  

Background: Pain is one of the most common clinical symptoms. Clinical treatment of pain is still a big problem. Therefore, it is necessary for researchers to look for treatments with fewer side effects. Plants have high biological importance and some of them can show antinociceptive activities. Esculin is one of the important derivatives of Fraxinus rhynchophylla plant bark. The purpose of this study is to investigate the antinociceptive effects of esculin and the possible mechanisms involved in it in adult male mice.

Methods: In this study, mice were divided into 5 groups, which include the control group, 3 groups receiving esculin (with doses of 10, 20 and 40 mg/kg) and the indomethacin group (5 mg/kg). Pain induction was done using writhing test. To check the analgesic activity, 30 minutes after the injection of the above compounds in the respective groups, 0.6% acetic acid (10 mg/kg) was injected and the behavior of the mice was observed for 30 minutes to count the number of writhes. took Then, the most effective dose of esculin (40 mg/kg) was selected to investigate the involved mechanisms. In order to investigate the possible role of the systems involved in analgesia caused by esculin, pretreatment with naloxone (opioidergic receptors antagonist, 2 mg/kg), atropine (cholinergic receptors antagonist, 1 mg/kg), chlorpheniramine (H1 histaminergic receptors antagonist, 20 mg/kg), cimetidine (H2 histaminergic receptors antagonist, 12.5 mg/kg), flumazenil (GABAergic receptors antagonist, 5 mg/kg), cyproheptadine (serotonergic receptors antagonist, 4 mg/kg) and yohimbine (adrenergic receptors antagonist, 2 mg/kg) were administered 15 minutes before the injection of esculin. Then, 15 minutes after the injection of esculin, acetic acid was injected and the number of writhes was calculated for 30 minutes. All injections were done intraperitoneally.

Results: The results showed that esculin has a dose-dependent antinociceptive effect in pain induced by the writhing test (0/05>P(. Also, in the groups pretreated with naloxone, atropine, flumazenil and yohimbine, the antinociceptive effects decreased significantly (0/05>P(.

  

The effects of co-administration of Doxorubicin and green synthesized ZnO    on the osteogenic differentiation of bone marrow derived mesenchymal stem cells; in vitro and in silico assessment

Abstract

The chemotherapy drug Doxorubicin (DOXO) can inflict substantial bone damage on cancer patients. While the mechanisms behind DOXO-induced osteoporosis remain incompletely elucidated, evidence suggests that DOXO may hinder the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) through the Bone Morphogenetic Protein-2 (BMP-2)/Drosophila mothers against decapentaplegics (SMAD) signaling pathway. Notably, Zinc Oxide Nanoparticles (ZnO   ) have proven effective in promoting bone formation, mineralization, and osteoblastic cell proliferation. Recently, green-synthesized ZnO    exhibit immense potential for various biomedical applications due to their biocompatibility and biodegradability.

This study investigates the effects of co-administration of DOXO and green synthesized the ZnO    from hydroalcoholic extract of Cercis siliquastrum (C.S) on the osteogenic differentiation of BMSCs; in vitro and in silico assessments. ZnO    were synthesized from hydroalcoholic extract of C.S and characterized both qualitatively and quantitatively. To determine their effect on osteogenic differentiation, BMSCs were cultured in media with and without ZnO    (10 µg/ml) and DOXO (10 nmol) for 14 days. The transcription of genes involved in osteogenic differentiation of BMSCs was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR). The impact of ZnO    on osteoblast function and bone formation was assessed by ALP enzyme and intracellular calcium deposition assays. To investigate the ability of the ZnO    to target BMPRs, an in silico molecular docking simulation was conducted using the descriptive-analytical method. AutoDock 4.2.6 software was employed to examine the binding interaction between the ZnO    and the active site of BMPRs.

The BMSCs groups treated with the ZnO    significantly increased the expression of osteogenic differentiation-related genes (BMP-2, runt-related transcription factor 2 (RUNX2), ALP and collagen type IA (COL1A). and intracellular calcium deposition. Also the most negative binding energy level (?G bind = -3.14 and -2.32 kcal/mol) demonstrated a propensity for binding to the active sites of both the type II receptor (BMPRII) and type I receptor (BMPRIa), Respectively.

Our research sheds valuable light on the mechanism underlying the osteogenic differentiation-inducing effects of a combined treatment of DOXO and the ZnO   , both in vitro and in silico. This finding could potentially pave the way for exploring novel strategies to prevent chemotherapy-induced osteoporosis.

Key words:

Doxorubicin, bone marrow mesenchymal stem cells, zinc oxide nanoparticles, Cercis siliquastrum, molecular docking, BMP2 signaling pathway

Introduction:

  

Method:

  

Result and Discussion:

  

Abstract

Background and Objective:  Depression, as a highly prevalent and major neuropsychiatric disorder, has physical and emotional symptoms. Postpartum depression (PPD) appears to be a harmful condition affecting mothers and their offspring negatively. Considering the impact of zinc on mood and its important role in the pathophysiology and therapy of depression, the present study was designed to evaluate the antidepressant-like effect of zinc oxide nanoparticles (ZnO   ) and possible mechanisms of action in the model of PPD in female mice.

Material and Methods:  Adult female mice were divided into groups of control, untreated depressed, depressed recipient of ZnO    (5, 10, 20 mg/kg) and fluoxetine (20 mg/kg). Model of postpartum depression was induced by intraperitoneal injection of progesterone (5 mg/kg, once daily for five consecutive days) and 3 days after stopping administration.  Then, depressive-like behavior was assessed 30 min following of  D by forced swimming test (FST). In another set of experiments, the possible involvement of the nitrergic, serotonergic, adenosinergic and glutamatergic systems in antidepressant-like effect of ZnO    were evaluated by pharmacological agents.

Results:  Induction of PPD model significantly increased immobility time in the FST (P<0.05). Administration of ZnO    (10 and 20 mg/kg) and fluoxetine (20 mg/kg) significantly improved depression and decreased immobility time in the FST (P<0.05), whereas lower dose of ZnO    (5 mg/kg) had no effect (P?0.05). There was no difference between groups in the number of crossings in the open-field test (OFT) (P?0.05). Moreover, antidepressant-like effect of effective dose of ZnO    (20 mg/kg) in the FST was significantly blocked by pretreatment of mice with L-arginine (750 mg/kg, a nitric oxide precursor), WAY100635 (0.1 mg/kg, a selective 5?HT_1A  receptor antagonist), caffeine (3 mg/kg, a non-selective adenosine receptors antagonist), and N-methyl-D-aspartate (NMDA) (75 mg/kg, NMDA receptor agonist) (P<0.05). In addition, the treatment of mice with L-NAME (10 mg/kg, a non-specific NOS inhibitor), adenosine (0.1 mg/kg, a non-selective adenosine receptors agonist), and MK-801 (0.05 mg/kg, NMDA receptor antagonist) significantly potentiated the action of sub-effective dose of ZnO    (5 mg/kg) and reduced immobility time in the FST (P<0.05).

Conclusion:  It is suggested that the antidepressant-like effect of ZnO    may be mediated by interaction with the nitrergic, serotoninergic, adenosinergic, and glutamatergic systems.

Keywords:  ostpartum depression, Zinc oxide nanoparticles, Forced swimming test, Mice.

Poor reproductive efficiency in dairy cows continues to be a major concern for the dairy industry worldwide. In the last few decades, genetic selection for milk production has been associated with decreased reproductive efficiency. The modern high-producing dairy cow partitions a greater proportion of available nutrients toward milk production at the expenses of body reserves and reproduction. On the other hand, incorrect detection of estrus is related to the loss of profit due to extended calving intervals, milk loss, and related veterinary costs. Considerable research efforts have focused on developing technologies to induce synchronized ovulation for timed artificial insemination (TAI) in beef and dairy cattle. The objective of the present study was to improve ovulation rate (OR), conception rate (CR) and pregnancy rate (PR) in lactating Holstein dairy cows by replacing the second gonadotropin releasing hormone (GnRH2) in Ovsynch and Co-synch protocols with human chorionic gonadotropin (hCG). Forty nine cows that had performed their first calving about 60 days ago were registered in the following groups after being confirmed to be healthy clinically: 1) The Ovsynch group (OVS; n=12): GnRH, 7 days, PGF2?, 56 hours, GnRH, 16-18 hours TAI; 2) The Co-synch group (COS; n=12): GnRH, 7 days, PGF2?, 72 hours, GnRH + TAI; 3) The Ovsynch + hCG (OVS-hCG; n=12): As OVS except that the GnRH2 was replaced with a dose of hCG (1500 i.u., i.m.); 4) The Co-synch + hCG (COS-hCG; n=13): As COS except that the GnRH2 was replaced with a dose of hCG (1500 i.u., i.m.). Ovaries of all animals were scanned ultrasonographically on days 9, 10 and 11 after beginning of the protocols (day 0, the beginning day of the protocols) to record ovulation. Ovulation was defined as the disappearance (from one scanning session to the next) of a previously identified follicle greater than or equal to 8 mm in diameter. Pregnancy diagnosis was performed by transrectal ultrasonography on days 30 ± 1 and 42 ± 1 after TAI for determining CR an PR, respectively. The results of the current study showed that the highiest OR, CR, and PR were achieved in OVS, OVS, and OVS, and the lowest OR, CR, and PR in COS, OVS-hCG, and COS-hCG, respectively, but the differences were not statistically significant (P > 0.05). In conclusion, the results of the present study demonstrated that replacing GnRH2 with hCG in Ovsynch and Co-synch protocols did not improve OR, CR, or PR (P=0.08). Conducting the experiment in a larger scale may reveal more clear results.