Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
25
4
2022
04
01
Saffron nephroprotective effects against medications and toxins: A review of preclinical data
419
434
EN
Batool
Zarei
Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
zareb891@mums.ac.ir
Sepideh
Elyasi
0000-0001-9857-1175
Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
elyasis@mums.ac.ir
10.22038/ijbms.2022.61344.13570
Toxin and drug-induced nephrotoxicity (DIN) account for about 25% of all acute kidney injury cases and are associated with morbidity and increased utilization of healthcare services. No approved preventive compound is available for DIN. Saffron (Crocus sativus) has important biological properties like antioxidant and anti-inflammatory effects. The protective effects of saffron and its main constituents in different tissues including the brain, heart, liver, kidney, and lung have been confirmed against some toxic materials or drugs in animal studies. This review covers all aspects of saffron’s preventive and therapeutic effects against toxins and DIN including proposed mechanism of action, dosing schedule, and effects on renal biomarkers and histological changes. PubMed, Embase, Scopus, and Web of Science databases were searched by these search terms: “saffron” OR “Crocus sativus” OR “crocetin” OR “crocin “OR “safranal” AND “Drug induced nephrotoxicity” OR “Renal Injury” OR “Kidney Injury” OR “Nephrotoxicity”. All 25 relevant in vitro and in vivo studies up to the date of publication were included. Promising protective effects were reported particularly on aminoglycosides, cisplatin, and ethanol. Saffron and its constituents significantly prevented biochemical and histopathological changes, mediating via antioxidant, anti-apoptosis, and anti-inflammatory effects. Despite success in animal models, no human study is available in this field and further well-designed clinical trials are necessary for better judgment.
Acute kidney injury,Crocin,Crocus,Safranal,Saffron
https://ijbms.mums.ac.ir/article_20007.html
https://ijbms.mums.ac.ir/article_20007_4db39b5c5e2d2bf53f46b7665989eb96.pdf
Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
25
4
2022
04
01
Neutrophil depletion reduces interstitial cajal-like cell injury and alleviates inflammation-induced motor dysfunction in guinea-pig gallbladder during acute cholecystitis
435
441
EN
Li
Zhang
Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Yuzhong District, Chongqing 400016, China
zhangt0712@126.com
Bin
Yang
Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 238, Jiefang Road, Wuhan 430060, Hubei Province, China
zkaeagle@163.com
Yong
Xiao
Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 238, Jiefang Road, Wuhan 430060, Hubei Province, China
xiaoyue0831@163.com
Bingqiang
Zhang
Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Yuzhong District, Chongqing 400016, China
zhbingqiang@163.com
Baoping
Yu
Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 238, Jiefang Road, Wuhan 430060, Hubei Province, China
yubp62@163.com
Youlin
Kuang
kyl361@163.com
Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, No. 1, Youyi Road, Yuzhong District, Chongqing 400016, China
kyl361@163.com
10.22038/ijbms.2022.59415.13195
<em><strong>Objective(s):</strong></em> Gallbladder interstitial Cajal-like cells (ICLCs) are known as some of the players in the complex motility mechanisms affecting gallbladder motility. This study aims to explore the mechanism of guinea-pig gallbladder motility disorders during Acute Cholecystitis (AC), focusing on the relationships between neutrophil alterations, gallbladder ICLCs, and smooth muscle contractility.<br /><em><strong>Materials and Methods:</strong></em> Forty-eight guinea pigs were randomly divided into four groups: normal, sham, common bile duct ligation (CBDL), and anti-PMN (anti-polymorphonuclear antibody treated +CBDL). Hematoxylin and eosin-stained slides from each gallbladder sample were examined for inflammation, and myeloperoxidase (MPO) activity was evaluated. The contractile response of gallbladder muscle to Ach, CCK-8, and KCl was registered by a tension transducer, and ultrastructure features of ICLCs were observed.<br /><strong><em>Results:</em></strong> Pretreatment with anti-PMN significantly reduced the circulating neutrophils by 80% and also considerably decreased the gallbladder MPO activity by 52.9% compared with the CBDL group (P<0.05). After adding Ach, CCK-8, and KCl, the contraction ability in CBDL and anti-PMN groups was lower than those of normal and sham groups (P<0.05), and they were increased substantially in the anti-PMN group compared with the CBDL group (P<0.05). Transmission electron microscopy confirmed that the cytoplasm of the neutrophils was full of granules, and neutrophils contacted closely with ICLCs. The ultrastructure of ICLCs in the anti-PMN group was less inflamed and the endoplasmic reticulum was mildly dilated, and cell processes also increased.<br /><em><strong>Conclusion:</strong></em> Anti-PMN could relieve the ultrastructure injury of ICLCs and alleviate gallbladder dysmotility during AC. Neutrophils may damage gallbladder ICLCs at first followed by dysmotility.
Common bile duct ligation,Gallbladder dysmotility,Guinea pigs,Interstitial cajal-like cells,Neutrophils,Ultrastructure features
https://ijbms.mums.ac.ir/article_20008.html
https://ijbms.mums.ac.ir/article_20008_bf5f68e2260c0e1ebbfff9744c630859.pdf
Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
25
4
2022
04
01
Recombinant PBP2a/autolysin conjugate as PLGA-based nanovaccine induced humoral responses with opsonophagocytosis activity, and protection versus methicillin-resistant Staphylococcus aureus infection
442
450
EN
Setareh
Haghighat
0000-0002-6605-5245
Department of Microbiology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
setareh_haghighat@yahoo.com
Seyed Davar
Siadat
0000-0002-6892-5603
Department of Mycobacteriology & Pulmonary Research, Microbiology Research Center, Pasteur Institute of Iran, Tehran, Iran
d.siadat@gmail.com
Abbas
Akhavan Sepahi
Department of Microbiology, Faculty of Basic Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran
akhavansepahy@gmail.com
Mehdi
Mahdavi
0000-0003-4478-5957
Advanced Therapy Medicinal Product (ATMP) Department, Breast Cancer Research Center, Motamed Cancer Institute, Academic Center for Education, Culture and Research(ACECR), Tehran, Iran
mahdavivac@gmail.com
10.22038/ijbms.2022.59992.13303
<em><strong>Objective(s):</strong></em> Methicillin-resistant Staphylococcus aureus (MRSA) reasons extreme infections, can resist various conventional antimicrobial agents, and cause morbidity and mortality worldwide. Vaccination seems to help modulate MRSA infections. Nanovaccine is considered a novel strategy in vaccine technology. The primary purpose of the present study was to develop a conjugate vaccine based on recombinant PBP2a and MRSA autolysin formulated in PLGA as a nanoparticle capable of enhancing protective responses against MRSA in the murine model.<br /><em><strong>Materials and Methods:</strong></em> Recombinant PBP2a and autolysin have been expressed and purified by nickel-nitrilotriacetic acid (Ni-NTA) affinity column and characterized by SDS-PAGE and western blot. PLGA was bound to recombinant proteins by using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC) and adipic acid dihydrazide (ADH) as a linker and spacer, respectively. Conjugation of recombinant proteins to PLGA was confirmed by the AFM assay, zeta potential, and size distribution, and its efficacy was evaluated in mice. Total IgG, IgG1, IgG2a, IgG2b, and IgM titers were analyzed to assess immune responses. Lastly, the bioactivity of antibodies was tested by using the opsonophagocytosis assay. <br /><em><strong>Results:</strong></em> Mice immunized with the r-PBP2a-r-autolysin–PLGA nanovaccine led to increased levels of opsonic antibodies and IgG1, IgG2a, IgG2b, and IgM when compared with other experimental groups. Our results confirmed that vaccination with nanovaccine could reduce the mortality rate against the sub-lethal dose of MRSA challenge. Furthermore, the nanovaccine could eliminate MRSA from the kidney of infected mice. <br /><em><strong>Conclusion:</strong></em> This study may provide valuable insights into the protective power of the r-PBP2a-r-autolysin–PLGA conjugate vaccine against MRSA infection.
Autolysin,Methicillin-resistant - Staphylococcus aureus,Nanovaccine,PBP2a,PLGA
https://ijbms.mums.ac.ir/article_20058.html
https://ijbms.mums.ac.ir/article_20058_76d36599fe05d79de42884471af4fa25.pdf
Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
25
4
2022
04
01
Acupuncture points injection mitigates chronic pain through transient receptor potential V1 in mice
451
459
EN
Hsien-Yin
Liao
0000-0002-3853-8450
College of Chinese Medicine, School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung 40402, Taiwan
jamesliao1076@hotmail.com
Ming-Chia
Lin
0000-0002-0361-3334
Department of Nuclear Medicine, E-DA Hospital, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan
ed101186@edah.org.tw
Yi-Wen
Lin
0000-0001-7204-8837
College of Chinese Medicine, Graduate Institute of Acupuncture Science, China Medical University, Taichung 40402, Taiwan
yiwenlin@mail.cmu.edu.tw
10.22038/ijbms.2022.60121.13327
<em><strong>Objective(s): </strong></em>Tissue injury in peripheral sites can result in long-term potentiation in nociceptive neurons and surrounding glial cells, potentially resulting in the development of chronic inflammatory pain (CIP). Acupoint injection (AI) is similar to Western phototherapy, which injects solutions at specific sites to mitigate chronic pain. AI has shown greater benefits compared with acupuncture. In this study, we examined the therapeutic effect and explored the underlying mechanisms of AI in mice CIP model. <br /><em><strong>Materials and Methods: </strong></em>We injected thrice complete Freund’s adjuvant (CFA) into the mouse’s hind paw to induce CIP. <br /><em><strong>Results:</strong></em> We found that, after two weeks, CFA injection significantly induced mechanical and thermal hyperalgesia which were attenuated by AI treatment. Transient receptor potential V1 (TRPV1) channels and associated molecules were all increased in CIP in mice dorsal root ganglion (DRG), spinal cord (SC), thalamus, and somatosensory cortex (SSC). The aforementioned molecules were mitigated in AI and Trpv1 knockout mice. Furthermore, Iba1-positive cells (microglial marker) were also potentiated and shared a similar tendency with TRPV1.<br /><em><strong>Conclusion:</strong></em> These findings suggest that AI can alleviate chronic pain by reducing TRPV1 overexpression in both neuronal and microglial cells. Our results suggest new potential therapeutic targets for AI in chronic pain.
Acupuncture points injection,Chronic inflammatory pain,Dorsal root ganglion,Iba1,Somatosensory cortex TRPV1
https://ijbms.mums.ac.ir/article_20079.html
https://ijbms.mums.ac.ir/article_20079_8a516bd703a54e1dbfd0c2a5bf65c0ca.pdf
Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
25
4
2022
04
01
Protective effect of crocin on hemodynamic parameters, electrocardiogram parameters, and oxidative stress in isolated hearts of rats exposed to PM10
460
467
EN
Esmat
Radmanesh
0000-0003-1369-6580
Research Center for Environmental Contaminants (RCEC), Abadan University of Medical Sciences, Abadan, Iran
esmatradmanesh33@gmail.com
Mahin
Dianat
0000-0002-0305-5715
Persian Gulf Physiology Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
dianat@ajums.ac.ir
Mohammad
Badavi
0000-0003-2290-8565
Persian Gulf Physiology Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
badavim@yahoo.com
Gholamreza
Goudarzi
0000-0001-5387-0761
Air Pollution and Respiratory Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
ghgoodarzi@ajums.ac.ir
Seyyed Ali
Mard
0000-0002-4323-1672
Persian Gulf Physiology Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
alimard77@gmail.com
Maryam
Radan
0000-0002-5853-0392
Persian Gulf Physiology Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
radan.maryam@yahoo.com
10.22038/ijbms.2022.61163.13533
<em><strong>Objective(s): </strong></em>Exposures to particulate matter (PM) have been related to increased risk for cardiovascular health effects and can promote cardiac ischemia and oxidative stress. Crocin has strong antioxidant properties and stress-reducing effects. Therefore, this study considered the effect of crocin on cardiovascular parameters in rats exposed to PM10.<br /><em><strong>Materials and Methods:</strong></em> Forty Wistar rats (male, 250–300 g) were grouped as control, receiving normal saline and crocin, receiving PM10, receiving PM10+Crocin. Instillation of PM10 into the trachea was done. Forty-eight hours after exposure to the normal saline or PM, the heart was separated. Hemodynamic and electrophysiological factors were measured. The levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase activity (CAT), malondialdehyde (MDA), xanthine oxidase, were evaluated by kits.<br /><em><strong>Results: </strong></em>The voltage of the QRS complex was significantly reduced and PR and QTc intervals increased in PM10 groups. Hemodynamic parameters before ischemia and in the ischemic-reperfusion stage, in the PM10 group, showed a significant decrease. In the ischemic hearts of the PM10 group, a significant decline in the activity of CAT, SOD, and GPx, and a significant increase in MDA and XOX enzymes activity were observed, and crocin improved all of these factors. <br /><strong><em>Conclusion:</em></strong> Cardiac ischemia causes abnormal hemodynamic factors of the heart, which are exacerbated by PM10 and further reduce the heart’s contractile strength. Increased oxidative stress due to PM10 is probably one of the important reasons for these changes. This study suggests that the use of antioxidants such as crocin improves the cardiovascular adverse effects of myocardial ischemia and PM10 exposure.
Crocin,Electrophysiological factors,Hemodynamic parameters,Oxidative stress,Particulate Matter
https://ijbms.mums.ac.ir/article_20086.html
https://ijbms.mums.ac.ir/article_20086_b2860d9d76cb90990108ed9150140aa8.pdf
Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
25
4
2022
04
01
Genotypic and phenotypic characterization of Escherichia coli isolated from indigenous individuals in Malaysia
468
473
EN
Vanitha
Mariappan
0000-0002-2351-1597
Centre of Toxicology and Health Risk Studies (CORE), Faculty of Health Sciences, Universiti Kebangsaan Malaysia, 50300 Kuala Lumpur, Malaysia
vanitha.ma@gmail.com
Soo Tein
Ngoi
Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
ngoisootein@um.edu.my
Yvonne Ai Lian
Lim
Department of Parasitology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
limailian@um.edu.my
Romano
Ngui
Department of Parasitology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
romano@um.edu.my
Kek Heng
Chua
Department of Biomedical Science, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
khchua@um.edu.my
Cindy Shuan Ju
Teh
Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
cindysjteh@um.edu.my
10.22038/ijbms.2022.61612.13637
<em><strong>Objective(s):</strong></em> The occurrence of asymptomatic verocytotoxin (VT)-producing Escherichia coli (VTEC) infections among humans in recent years is posing a high risk to public health. Thus, the role of asymptomatic human carriers as a source of dissemination should not be underestimated. This study aimed to elucidate the phenotypic and genotypic characteristics of E. coli in the stool samples collected from indigenous individuals in Malaysia. <br /><em><strong>Materials and Methods:</strong></em> E. coli strains (n=108) were isolated from stool samples obtained from 41 indigenous individuals. All strains were subjected to Repetitive Extragenic Palindromic-Polymerase Chain Reaction (REP-PCR) typing and confirmation of VTEC variants. Non-duplicate strains were selected based on REP-PCR profiles and further subjected to antimicrobial susceptibility test (AST). The genotypic and phenotypic characteristics of the strains were then correlated with the demographic data of the subjects. <br /><em><strong>Results: </strong></em>A total of 66 REP-PCR profiles grouped in 53 clusters (F=85%) were obtained. Four genetically distinct strains were confirmed as VTEC (eaeA-positive). The predominant resistance was against ampicillin (34.2%), followed by trimethoprim-sulfamethoxazole (32.9%), ampicillin-sulbactam (5.5%), and ciprofloxacin (1.4%). All isolates were sensitive to amoxicillin-clavulanate, cefuroxime, ceftriaxone, imipenem, and meropenem. <br /><em><strong>Conclusion:</strong></em> Genetically diverse E. coli and VTEC strains were found to colonize the intestines of the indigenous populations. This study is important for the prospective surveillance of E. coli among the indigenous individuals in Malaysia, especially in asymptomatic VTEC infection and antimicrobial resistance phenomenon.
Genotypic,Indigenous,Malaysia,Phenotypic,Verocytotoxin (VT)-producing Escherichia coli (VTEC)
https://ijbms.mums.ac.ir/article_20006.html
https://ijbms.mums.ac.ir/article_20006_e9bea77f15cb9e7411a4164514cd9121.pdf
Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
25
4
2022
04
01
Induced overexpression of MARCH-1 in human macrophages altered to M2 phenotype for suppressing inflammation process
474
482
EN
Zivar
Zangeneh
0000-0002-5747-2506
Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
zangenehzivar@yahoo.com
Gholamreza
Khamisipour
0000-0002-5773-9012
Department of Hematology, School of Para Medicine, Bushehr University of Medical Sciences, Bushehr, Iran
ghr.khamisi@gmail.com
Alireza
Andalib
0000-0002-2032-6281
Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
andalib@med.mui.ac.ir
10.22038/ijbms.2022.62893.13902
<em><strong>Objective(s):</strong></em> The M1 macrophage is characterized by enhanced pro-inflammatory cytokines production, whereas macrophage (M2) has anti-inflammatory features. Macrophage polarization as a therapeutic target for controlling immune responses could be performed by gene transduction to control the regulation of exaggerated innate/adaptive immune responses. <br /><em><strong>Materials and Methods: </strong></em>Macrophages were prepared from THP-1 cell line and human monocytes that were transduced with (Membrane-Associated RING-CH-type finger) MARCH-1 viral lentivector produced in HEK-293T cells. RT-PCR and Western blotting confirmed MARCH-1 gene transduction. Cytokine production, CD markers assay, macrophage phagocytosis potential activity and mixed leukocyte reaction (MLR) with CFSE were performed for M1/M2 plasticity.<br /><em><strong>Results: </strong></em>The mean fluorescent intensity of HLA-DR and CD64 expression reduced in MARCH-1+ transduced macrophage population. However, CD206 and CD163 expression increased in these macrophages. The concentrations of IL-6, TNF-α and iNOS were decreased in MARCH-1 transduced cells, and TGF-β production showed an augmentation in concentration. Western blotting and real-time PCR measurement confirmed that the expression levels of MARCH-1 protein and arginase-1 enzyme were increased in transduced macrophages.<br /><em><strong>Conclusion:</strong></em> The anti-inflammatory features of MARCH-1 revealed the reduced levels of pro-inflammatory factors and maintained M2 phenotype characterized by high levels of scavenger receptors. Therefore, targeting MARCH-1 in monocytes/macrophages could represent a new autologous cell-based therapies strategy for inflammatory conditions.
INOS,Macrophage,MARCH-1,Polarization,TGF-beta
https://ijbms.mums.ac.ir/article_20078.html
https://ijbms.mums.ac.ir/article_20078_f863392455a03f78b62b1a71ced77fd2.pdf
Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
25
4
2022
04
01
Epigallocatechin-3-gallate alleviates type 2 diabetes mellitus via β-cell function improvement and insulin resistance reduction
483
488
EN
Tiantian
Zhu
0000-0001-9017-6608
College of Pharmacy, Xinxiang Medical University, Xinxiang, China
zhutt@xxmu.edu.cn
Minghui
Li
0000-0001-9017-6680
College of Pharmacy, Xinxiang Medical University, Xinxiang, China
941805101@qq.com
Moli
Zhu
College of Pharmacy, Xinxiang Medical University, Xinxiang, China
molizhu@xxmu.edu.cn
Xu
Liu
College of Pharmacy, Xinxiang Medical University, Xinxiang, China
1085304847@qq.com
Keke
Huang
College of Pharmacy, Xinxiang Medical University, Xinxiang, China
2998515542@qq.com
Wenru
Li
College of Pharmacy, Xinxiang Medical University, Xinxiang, China
1372626478@qq.com
Shuang-Xi
Wang
College of Pharmacy, Xinxiang Medical University, Xinxiang, China
shuangxiwang@sdu.edu.cn
Yaling
Yin
Henan International Joint Laboratory of Cardiovascular Remodeling and Drug Intervention, Xinxiang, China
hnpdsyyl@163.com
Peng
Li
orcid.org/0000-0002-9455-9643
College of Pharmacy, Xinxiang Medical University, Xinxiang, China
071021@xxmu.edu.cn
10.22038/ijbms.2022.58591.13016
<em><strong>Objective(s):</strong></em> Epigallocatechin-3-gallate (EGCG) has a good therapeutic effect on type 2 diabetes mellitus (T2DM). This work was designed to explore EGCG’s effectiveness in insulin resistance (IR) and pancreas islet β-cell function in a rat model of T2DM. <br /><em><strong>Materials and Methods:</strong></em> Eight-week-old male Sprague Dawley rats were randomly divided into 6 groups, including the Control (normal diet), Diabetes (high-sucrose high-fat [HSHF] diet combined with tail vein injection of streptozotocin [STZ] for T2DM induction) and Treatment Diabetic rats which were treated with metformin [500 mg/kg/d] or EGCG [25, 50 or 100 mg/kg/d] intragastric administration for 10 weeks. With the exception of control animals, the other groups were fed the HSHF diet. EGCG’s effects on IR and insulin secretion were assessed by measuring body weights, and fasting blood glucose (FBG), postprandial blood glucose (PBG) and insulin levels. The morphological and molecular changes of pancreas islet β-cells were examined by hematoxylin-eosin (H&E) staining, transmission electron microscopy (TEM) and immunofluorescence.<br /><em><strong>Results: </strong></em>Rats fed the HSHF diet combined with STZ treatment had increased body weights and blood glucose amounts, accompanied by IR and impaired β-cell function, induced T2DM, and EGCG dose-dependently restored the above indicators. Additionally, EGCG upregulated the pancreatic transcription factors pancreatic duodenal homeobox protein-1 (PDX-1) and musculoaponeurotic fibrosarcoma oncogene homolog A (MafA).<br /><em><strong>Conclusion: </strong></em>These results suggest that EGCG reduces blood glucose amounts, and improve IR and islet β-cell disorder in T2DM.
Epigallocatechin-3-gallate,insulin resistance,Insulin secretion,Pancreatic duodenal homeobox protein-1,Type 2 diabetes mellitus β-cell
https://ijbms.mums.ac.ir/article_20101.html
https://ijbms.mums.ac.ir/article_20101_93ba920e5017188fc377b0eb449a9397.pdf
Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
25
4
2022
04
01
Activation of apoptosis and G0/G1 cell cycle arrest along with inhibition of melanogenesis by humic acid and fulvic acid: BAX/BCL-2 and Tyr genes expression and evaluation of nanomechanical properties in A375 human melanoma cell line
489
496
EN
Mitra
Salehi
0000-0001-8061-1255
Student Research Committee, Qazvin University of Medical Sciences, Qazvin, Iran
mitra.salehi1374@gmail.com
Hossein
Piri
0000-0001-8402-7742
Department of Biochemistry and Genetics, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
hpiri@qums.ac.ir
Alireza
Farasat
Cellular and Molecular Research Center, Research Institute for Prevention of Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran
farasat8@gmail.com
Babak
Pakbin
Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran
babak.pakbin@gmail.com
Nematollah
Gheibi
0000-0001-7503-0894
Cellular and Molecular Research Center, Research Institute for Prevention of Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran
gheibi_n@yahoo.com
10.22038/ijbms.2022.60651.13444
<em><strong>Objective(s):</strong></em> Humic acid (HA) and Fulvic acid (FA) are major members of humic substances, which are extracted from organic sources including soil and peat. The pro-apoptotic and anti-melanogenic effects of HA and FA at the cellular and molecular levels in the A375 human melanoma cell line were examined in this study. <br /><em><strong>Materials and Methods: </strong></em>The cytotoxicity effect of HA and FA were evaluated by cell viability assay. Apoptosis and cell cycle were investigated by flow cytometry. Real-time PCR was carried out to measure the expression of BAX, BCL-2, and Tyr genes. Moreover, the changes in nanomechanical properties were determined through atomic force microscopy (AFM). <br /><em><strong>Results: </strong></em>It was found that HA and FA decrease cell viability with an IC50 value of 50 µg/ml (dose-dependent) for 14 hr, arrested cells in the G0/G1 phase, and increased the sub-G1 phase (induce apoptosis). Based on the AFM analysis, Young’s modulus and adhesion force values were increased, also ultrastructural characteristics of cells were changed. Results of Real-time PCR revealed that HA and FA lead to a decrease in the expressions of BCL-2 and Tyr genes, and increase the BAX gene expression.<br /><strong><em>Conclusion:</em></strong> These results exhibited that HA and FA possess pro-apoptotic effects through increasing the BAX/ BCL-2 expression in A375 cells. These molecular reports were confirmed by cellular nanomechanical assessments using AFM and flow cytometry. In addition, HA and FA inhibited melanogenesis by decreasing the expression of the Tyr gene. It is worthwhile to note that, HA and FA can be regarded to design new anti-cancer and anti-melanogenesis products.
Apoptosis,Bax,Bcl-2,Fulvic acid,Humic acid,Melanoma,Tyrosinase
https://ijbms.mums.ac.ir/article_20105.html
https://ijbms.mums.ac.ir/article_20105_8a03a0b885622810cedf2ac98a654c3c.pdf
Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
25
4
2022
04
01
Influence of ethanolic extract of Allium sativum on TP53 gene and its anticancer potential in N-Nitrosodiethylamine (NDEA)-induced hepatocellular carcinoma in male albino rats
497
505
EN
Godwin Offumobi
Ogar
Cancer Research and Infectious Disease Unit, Department of Cell Biology and Genetics, Faculty of Science, University of Lagos, Akoka, Lagos
ogar.offumobi@gmail.com
Joseph Bamidele
Minari
0000-0001-8346-9936
Cancer Research and Infectious Disease Unit, Department of Cell Biology and Genetics, Faculty of Science, University of Lagos, Akoka, Lagos
jminari@unilag.edu.ng
Adebayo Joseph
Bello
Cancer Research and Infectious Disease Unit, Department of Cell Biology and Genetics, Faculty of Science, University of Lagos, Akoka, Lagos
bayolinks@gmail.com
Janet
Chiwetalu
Cancer Research and Infectious Disease Unit, Department of Cell Biology and Genetics, Faculty of Science, University of Lagos, Akoka, Lagos
janetoluwakemi022@gmail.com
Oluwafunto Eunice
Omogunwa
Cancer Research and Infectious Disease Unit, Department of Cell Biology and Genetics, Faculty of Science, University of Lagos, Akoka, Lagos
funmimi6@gmail.com
Oluwadamilola Suzan
Oshikoya
Cancer Research and Infectious Disease Unit, Department of Cell Biology and Genetics, Faculty of Science, University of Lagos, Akoka, Lagos
ooshikoya@yahoo.com
Micheal Tobiloba
Otaru
Cancer Research and Infectious Disease Unit, Department of Cell Biology and Genetics, Faculty of Science, University of Lagos, Akoka, Lagos
motaru@yahoo.com
Chioma Anastacia
Anyanele
Cancer Research and Infectious Disease Unit, Department of Cell Biology and Genetics, Faculty of Science, University of Lagos, Akoka, Lagos
anyanelechiomaannas@gmail.com
10.22038/ijbms.2022.62295.13787
<em><strong>Objective(s):</strong></em> Cancer is a group of genetic disorders in which the behavior of the cell is disturbed by mutation and other abnormalities thereby posing as the leading cause of morbidity and mortality globally. Hepatocellular Carcinoma (HCC) is the most common form of liver cancer, highly aggressive with high mortality and incidence rate; and has limited therapeutic options. Most of the conventional cancer chemotherapeutics are associated with undesirable side effects, toxicity, chemoresistance, and high treatment cost, driving the need for a safer and more effective treatment alternative. Medicinal plants and herbs have shown very promising anti-cancer properties which are important for cancer treatment due to their multiple chemical compounds. <br /><em><strong>Materials and Methods:</strong></em> Qualitative screening of the ethanolic extractof Allium sativum was conducted showing the different phytochemicalspresent. The levels of liver function and hematological parameters wasdetermined via spectrophotometric analysis. Polymerase Chain Reaction techniquewas used to assess the gene patterns of Tumorsuppressor p53 (TP53).<br /><em><strong>Results:</strong></em> Phytochemical analysis revealed that Allium sativum has properties that antagonize the proliferating process of carcinogenesis in the liver. The NDEA-group showed significant distortion in the liver architecture characterized by vascular congestion of blood sinusoids, cirrhosis, and congestive hepatopathy while the treated groups showed a reduction in the abnormalities and malignant formation. The treated group showed a significant (P<0.05) increase and restored activities of Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), Bilirubin and hematological parameters (RBCs, WBCs, and Platelets). TP53 gene amplification was significantly (P<0.05) visible after treatment. <br /><em><strong>Conclusion:</strong></em> Ethanolic plant extract of A. sativum demonstrates its anticancer properties by improving the liver architecture, increasing the antioxidant defense systems, and activation of the tumor suppressor (TP53) gene. Garlic extract has anti-proliferating properties and can be used as an alternative mode of treatment and prevention for hepatocellular carcinoma.
Antineoplastic agents,carcinogens,Carcinoma,Diethylnitrosamine,Garlic,Hepatocellular,Medicinal,P53
https://ijbms.mums.ac.ir/article_19998.html
https://ijbms.mums.ac.ir/article_19998_2ca683158aab03106f27e718b9388e69.pdf
Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
25
4
2022
04
01
Metformin exerts synergistic anti-proliferative effects with Liraglutide in human umbilical vein endothelial cells (HUVECs)
506
513
EN
Amir
Shadboorestan
0000-0002-5695-8934
Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
a.shadboorestan@modares.ac.ir
Samane
Eftekhari
Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
samaneeftekhari73@gmail.com
Negar
Mottaghi-dastjerdi
Department of Pharmacognosy and Pharmaceutical Biotechnology, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran
mottaghi.n@iums.ac.ir
Rezvan
Shahparvari
Pharmaceutical Sciences Research Center, Tehran Medical Sciences, Islamic Azad University, Tehran Iran
shah1364.r@gmail.com
Parastoo
Tarighi
Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
tarighi.p@iums.ac.ir
Hoda
Jahandar
Pharmaceutical Sciences Research Center, Tehran Medical Sciences, Islamic Azad University, Tehran Iran
h.jahandar@iautmu.ac.ir
Homa
Faghihi
Department of Pharmaceutics, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran
faghihi.h@iums.ac.ir
Hamed
Montazeri
0000-0001-8532-4327
Department of Pharmacognosy and Pharmaceutical Biotechnology, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran
montazerighods.h@iums.ac.ir
10.22038/ijbms.2022.64117.14117
<em><strong>Objective(s):</strong></em> Metformin (Met) and Liraglutide (Lira) have been approved to treat type 2 diabetes mellitus and have cardioprotective effects. <br /><em><strong>Materials and Methods: </strong></em>Human umbilical vein endothelial cells (HUVECs) were incubated with Met, Lira, or their combination in this study. <br /><em><strong>Results:</strong></em> Results showed that the synergistic inhibitory effect of the two drugs on HUVECs proliferation was significant (75%) after 48 hr drug exposure. In addition, either Lira or Met alone had a marked tendency to inhibit the migration of HUVECs (42% and 39%). Almost a complete inhibition (97%) was demonstrated in combinational use after 48 hr treatment. After combining these two drugs, the apoptosis rate raised to 68%, which was a significant approval of synergistic apoptosis induction of Met and Lira. The combinational group indicated a substantial increase in VEGF, PDGF, and MMP-9 at 24 hr compared with the control. <br /><em><strong>Conclusion: </strong></em>This study showed that combination therapy with Lira and Met could effectively reduce cell proliferation, induce apoptosis, and inhibit cell migration in the HUVECs. This study provides evidence to support using Met in combination with Lira as a treatment option for patients with type-2 diabetes and cancer.
Angiogenesis,Cancer,HUVECs,liraglutide,Metformin
https://ijbms.mums.ac.ir/article_20066.html
https://ijbms.mums.ac.ir/article_20066_fb06da08618fd632b03c28ebf4cbf10d.pdf
Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
25
4
2022
04
01
Effects of cannabinoid and vanilloid receptor antagonists on nicotine induced relaxation response enhancement in rabbit corpus cavernosum
514
519
EN
İsmail Mert
Vural
0000-0002-1442-4766
Department of Pharmacology, Gulhane Faculty of Pharmacy, University of Health Sciences Turkey, Ankara/Turkey
imvural@yahoo.com
Gokce Sevim
Ozturk Fincan
Department of Medical Pharmacology, School of Medicine, Gazi University, Ankara/Turkey
gokcesevimozturk@yahoo.com
Derya Sebile
Koc
Department of Medical Pharmacology, School of Medicine, Gazi University, Ankara/Turkey
deryasebile@gmail.com
Yagmur
Okcay
Department of Pharmacology, Gulhane Faculty of Pharmacy, University of Health Sciences Turkey, Ankara/Turkey
yagmurokcay@gmail.com
Celil İlker
Askin
Department of Medical Pharmacology, School of Medicine, Gazi University, Ankara/Turkey
cilkeraskin@hotmail.com
Ayse Kubra
Kibar
Department of Medical Pharmacology, School of Medicine, Gazi University, Ankara/Turkey
aysekubrakibar@gmail.com
Sevil
Ozger Ilhan
Department of Medical Pharmacology, School of Medicine, Gazi University, Ankara/Turkey
soilhan@hotmail.com
Yusuf
Sarioglu
Department of Medical Pharmacology, School of Medicine, Istinye University, Istanbul/Turkey
ysarioglu@istinye.edu.tr
10.22038/ijbms.2022.62222.13772
<em><strong>Objective(s):</strong></em> Endocannabinoids and nicotine regulate the neurotransmitter release in different central and peripheral synapses. Various studies in the literature demonstrate the interaction between endocannabinoid and nicotinic systems, especially in the central nervous system. The interaction between nicotinic and endocannabinoid systems was investigated in this study. We aimed to show the effects of cannabinoid and vanilloid receptor antagonists on nicotine-induced relaxation response increases in rabbit corpus cavernosum.<br /><em><strong>Materials and Methods: </strong></em>From a total of seven male albino rabbits, three or four equal strips were cut from each corpus cavernosum and inserted in isolated organ baths. Tissues were contracted with phenylephrine (3×10−5 M). After contraction reached a plateau, strips were stimulated with EFS, and with the stabilization of EFS relaxation responses, 10-4 M of nicotine was administered to tissues. After that, in order to investigate the effects of AM251 (CB1 antagonist), AM630 (CB2 inverse agonist) or capsazepine (a vanilloid receptor antagonist) were given to different tissues, after the resting period.<br /><em><strong>Results: </strong></em>Nicotine (10−4 M) increased the EFS-induced relaxation responses (14.60%±2.94%, P<0.05). AM630 decreased the enhancement of nicotine-induced EFS relaxation responses (nicotine 10-4 M enhancement: 17.16%±3.19%; nicotine 10-4 M enhancement in the presence of AM630 10-6 M: 4.44%±3.43% P<0.05; n=6), whereas effects of AM251 and capsazepine were not significant. <br /><em><strong>Conclusion:</strong></em> In the present study, nicotine increased the amplitudes of EFS-induced relaxation responses probably via nicotinic acetylcholine receptors located on the nitrergic nerves of the corpus cavernosum. We showed the role of cannabinoid-like endo-ligands in nicotine-induced enhancement via CB2 receptors but not CB1 and VR1 receptors.
Cannabinoid receptors,Endocannabinoids,Nicotine,Penile erection,Smooth Muscle
https://ijbms.mums.ac.ir/article_20103.html
https://ijbms.mums.ac.ir/article_20103_f894bfca47317eb6d9072e87f9f7657d.pdf
Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
25
4
2022
04
01
Atractylodes chinensis volatile oil up-regulated IGF-1 to improve diabetic gastroparesis in rats
520
526
EN
Hongzeng
Li
Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China
Science and Technology, Qingdao, China
14187183242@qq.com
Yitong
Wang
Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China
2268526530@qq.com
Yuxin
Tian
Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China
Science and Technology, Qingdao, China
1692506563@qq.com
Feiyue
Tian
Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China
Science and Technology, Qingdao, China
2414623149@qq.com
Zhiyang
Xing
Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China
Science and Technology, Qingdao, China
879264054@qq.com
Yunfei
Wang
Shandong Xinhua Pharmaceutical Company Limited, Zibo, China
wangyunfei@xhzy.com
Meixing
Yan
0000-0001-9361-2492
Qingdao Women and Children’s Hospital, Qingdao, China
meixing@163.com
Yanling
Gong
https://orcid.org/00
Department of Pharmacy
College of Chemical Engineering
Qingdao University of Science and Technology
Qingdao, 266042 China
hanyu_ma@126.com
10.22038/ijbms.2022.60126.13339
<em><strong>Objective(s): </strong></em>Diabetic gastroparesis (DGP) is one of the main complications of diabetes, and more than half of diabetes cases are accompanied by gastroparesis. This study aims to explore the effect of Atractylodes chinensis volatile oil (ACVO) on DGP rats.<br /><em><strong>Materials and Methods:</strong></em> The rats were injected with STZ combined with a high-sugar and high-fat diet in an irregular manner to establish the DGP model. ACVO at different doses (9.11 mg/kg, 18.23 mg/kg, and 36.45 mg/kg) were given by intragastric administration. A mixture of cisapride and metformin was used as the positive control. At the end of the experiment, gastric emptying and intestinal propulsion were determined. Then the tissue samples and blood were taken from each group for serum analysis, western blot and immunopathological examination. <br /><em><strong>Results:</strong></em> After treatment with ACVO, body weight increased and blood glucose decreased when compared with rats in the DGP group. Gastric emptying and intestinal propulsion were accelerated, and gastric acid secretion increased. The serum insulin-like growth factor-1 (IGF-1) level was increased. Protein expressions and positive cells of IGF-1 receptor (IGF-1R), acetylcholine transferase (CHAT), and stem cell factors (SCF) in the stomach were significantly increased determined by western blot and immunofluorescence staining. The morphology and the number of interstitial cells of Cajal (ICCs) in the stomach were restored, determined by hematoxylin and eosin staining and immunohistochemical staining, respectively. <br /><em><strong>Conclusion:</strong></em> ACVO effectively alleviated DGP in rats, and its mechanism may be related to the up-regulation of IGF-1/IGF-1R signaling.
Atractylodes,Gastroparesis,Insulin-Like Growth Factor I,Interstitial cells of Cajal,Stem cell factor
https://ijbms.mums.ac.ir/article_20059.html
https://ijbms.mums.ac.ir/article_20059_b8bf06661820beb555ee295373a36f8f.pdf
Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
25
4
2022
04
01
Effect of Eucommia ulmoides leaves on hyperuricemia and kidney injury induced by a high-fat/high-fructose diet in rats
527
535
EN
Man
Gong
0000-0002-9256-1213
Henan University of Chinese Medicine, Henan Zhengzhou 450046, China
man.gong_2019@hactcm.edu.cn
Hong
Zhang
The Second Affiliated Hospital of Zhengzhou University, Henan Zhengzhou,450014, China
1033184142@qq.com
Qian
Xiao
Liu
Henan University of Chinese Medicine, Henan Zhengzhou 450046, China
lianyu1127@126.com
xia
qing
Li
Henan University of Chinese Medicine, Henan Zhengzhou 450046, China
1119106744@qq.com
Yang
Zhang
Henan University of Chinese Medicine, Henan Zhengzhou 450046, China
543767384@qq.com
jin
wei
Zhang
Henan University of Chinese Medicine, Henan Zhengzhou 450046, China
1625396534@qq.com
na
Huang
Henan University of Chinese Medicine, Henan Zhengzhou 450046, China
1257553831@qq.com
ying
an
Chen
Henan University of Chinese Medicine, Henan Zhengzhou 450046, China
cay0423@163.com
Liping
Dai
0000-0002-1910-7591
Henan University of Chinese Medicine, Henan Zhengzhou 450046, China
liping_dai@hactcm.edu.cn
Min
Zhi
Wang
0000-0003-4770-3814
Henan University of Chinese Medicine, Henan Zhengzhou 450046, China
zhmw123@163.com
10.22038/ijbms.2022.62681.13867
<em><strong>Objective(s):</strong></em> To investigate the protective and preventive treatment effects of Eucommia ulmoides leaves on a rat model of high-fat and high-fructose diet (HFFD) induced hyperuricemia and renal injury.<br /><em><strong>Materials and Methods:</strong></em> Network pharmacology and molecular-docking methods were used to predict the effects and action mechanisms of the major components of E. ulmoides leaves on hyperuricemia. Combining literature collection, we used SciFinder and the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and Analysis Platform to collect E. ulmoides leaf flavonoid and iridoid components. Swiss Target Prediction, Similarity ensemble approach (SEA), GeneCards, and the Online Mendelian Inheritance in Man (OMIM) database were used to obtain core targets, and the Search Tool for Recurring Instances of Neighbouring Genes (STRING) protein database was used as core target for gene ontology enrichment Set and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Molecular docking was applied to predict the pathways regulating the metabolism of uric acid. The selected targets and targeting efficacy were validated using a rat model of hyperuricemia and renal injury induced by a high-fat and high-fructose diet.<br /><em><strong>Results:</strong></em> A total of 32 chemical components with effective targets, which regulated the PI3K-AKT pathway and endocrine resistance, were collected. Molecular docking results showed that iridoids and flavonoids are bound to proteins related to inflammation and uric acid metabolism. In addition, it was verified via animal experiments that an E. ulmoides leaf extract ameliorated hyperuricemia, renal injury, and inflammation, which are closely related to the targets Interleukin- 6 (IL-6), Tumor necrosis factor-α (TNF-α), Toll-Like Receptor 4 (TLR4), and Glucose transporter 9 (GLUT9). <br /><em><strong>Conclusion:</strong></em> E. ulmoides leaf flavonoids and iridoids ameliorate hyperuricemia and uric-acid–induced inflammation through a multi-component, multi-target, and multi-pathway mechanism, which provides a theoretical basis for the development of therapeutics from E. ulmoides leaf components.
Eucommia ulmoides leaves,High-fat and high-fructose diet,Hyperuricemia,Kidney Injury,Molecular docking,Network pharmacology
https://ijbms.mums.ac.ir/article_20110.html
https://ijbms.mums.ac.ir/article_20110_f92c40504934d962cf1607e9fa866fe5.pdf
Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
25
4
2022
04
01
Antiproliferative and apoptotic activity of gemcitabine-lauric acid conjugate on human bladder cancer cells
536
542
EN
Hongxia
Wang
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
hxw1470@163.com
Zhiyu
Shao
College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China
zyshao@dhu.edu.cn
Zhiwen
Xu
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
xuzhiw1997@outlook.com
Binghao
Ye
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
y30190388@mail.ecust.edu.cn
Ming
Li
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
18217685667@163.com
Qiaoqiao
Zheng
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
y20170025@mail.ecust.edu.cn
Xingyuan
Ma
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
maxy@ecust.edu.cn
Ping
Shi
0000-0002-6904-2802
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
ship@ecust.edu.cn
10.22038/ijbms.2022.61118.13528
<em><strong>Objective(s): </strong></em>Gemcitabine is a first-line drug for the treatment of bladder cancer. One of the most important mechanisms of gemcitabine resistance is the low expression of cellular membrane transporter hENT1. Various derivatives containing fatty acid side chains have been developed in order to facilitate gemcitabine uptake and prolong its retention in cells, such as CP-4126. In this study, the anti-tumor effect and mechanism of a new derivative of gemcitabine named SZY-200 on bladder cancer cells were investigated. SZY-200 was assembled from the gemcitabine-lauric acid conjugate.<br /><em><strong>Materials and Methods:</strong></em> Antiproliferative activities of SZY-200 and lauric acid were evaluated using CCK-8 assay and clonogenic survival assay. The hENT1 inhibitor NBMPR was employed to determine the role of hENT1 in the apoptotic activity of GEM, CP-4126, and SZY-200. RT-qPCR, flow cytometry, fluorescence microscope, western blotting, and wound healing assay were used to study the mechanisms of SZY-200. The target genes were predicted using the BATMAN-TCM database.<br /><strong><em>Results: </em></strong>Our data showed that SZY-200 could inhibit the proliferation of bladder cancer cells by inducing cell cycle arrest and apoptosis. The inhibitory effects were comparable to gemcitabine and CP-4126. SZY-200 does not rely on hENT1 to help it enter bladder cancer cells. Also, we found that lauric acid could inhibit the proliferation of bladder cancer cells. SZY-200 could down-regulate the expressions of PPARG and PTGS2 which were related to the occurrence and development of bladder cancer.<br /><em><strong>Conclusion:</strong></em> SZY-200 has the same or more advantages as CP-4126 and could be an ideal candidate drug for further in vivo investigation.
Apoptosis,Cell cycle checkpoints,Gemcitabine,SLC29A1 protein,Urinary bladder neoplasms
https://ijbms.mums.ac.ir/article_20088.html
https://ijbms.mums.ac.ir/article_20088_e423ed5179cc59bbfc8f69a34672a776.pdf