فهرست مطالب

Basic Medical Sciences - Volume:24 Issue: 9, Sep 2021

Iranian Journal of Basic Medical Sciences
Volume:24 Issue: 9, Sep 2021

  • تاریخ انتشار: 1400/06/17
  • تعداد عناوین: 17
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  • Elahe Esmaeilpanah, Bibi Marjan Razavi, Hossein Hosseinzadeh * Pages 1159-1172

    Metabolic syndrome (MetS) has turned into a prevalent condition that has imposed a tremendous financial strain on public health care systems. It is believed that the MetS consists of four main factors (hypertension, dyslipidemia, hyperglycemia, and obesity) and may lead to cardiovascular events. Camellia sinesis, in the form of green tea (GT), is one of the most consuming beverages worldwide. Catechins are the dominant component of green tea leaves. Epigallocatechin gallate has the maximum potency. GT has been widely used as a supplement in various health conditions. As the oxidative stress pathway is one of the probable mechanisms of MetS etiologies and GT beneficial effects, GT may be a novel strategy to overcome the MetS. This review aims to reveal the probable pharmacological effects of GT on MetS. The last 10-year original articles on MetS parameters and GT have been gathered in this review. This manuscript has summarized the probable effects of green tea and its catechins on MetS and focused on each different aspect of MetS separately, which can be used as a basis for further investigations for introducing effective compounds as a way to interfere with MetS.It seems that GT can reduce MetS parameters commonly via anti-inflammatory and anti-oxidative mechanisms. Further clinical trials are needed to confirm the use of GT and its constituents for the treatment of MetS.

    Keywords: Diabetes, Dyslipidemia, green tea, Hypertension, metabolic syndrome, Obesity
  • Maryam Sadat Jalali, Alireza Sarkaki, Saeed Azandeh, Esrafil Mansouri, Mohammad Ghasemi Dehcheshmeh, Ghasem Saki * Pages 1173-1181
    Objective(s)
    Human Wharton’s jelly-derived mesenchymal stem cells (hWJ-MSCs) have been recognized as a potential tool to replace damaged cells by improving the survival of the dopaminergic cells in Parkinson’s disease (PD). In this study, we examined the effects of hWJ-MSCs and associated with L-dopa/carbidopa on motor disturbances in the PD model.
    Materials and Methods
    PD was induced by injection of 6-hydroxydopamine (6-OHDA) (16 μg/2 μl into medial forebrain bundle (MFB)). Sham group received a vehicle instead of 6-OHDA. PD+C group received hWJ-MSCs twice on the 14th and 28th days post PD induction. PD+C+D group received hWJ-MSCs and also L-dopa/carbidopa (10/30 mg/kg). PD+D group received L-dopa/carbidopa alone. Four months later, motor activities (the parameters of  locomotor and muscle stiffness) were evaluated, dopaminergic neurons were counted in substantia nigra pars compacta (SNc), the level of dopamine (DA), and tyrosine hydroxylase (TH) were measured in the striatum.  
    Results
    Data indicated that motor activities, the number of dopaminergic neurons, and levels of DA and TH activities were significantly reduced in PD rats as compared to the sham group (p <0.001). However, the same parameters were improved in the treated groups when compared with the PD group (p
    Conclusion
    The chronic treatment of PD rats with hWJ-MSCs and L-dopa/carbidopa, improved motor activity, which may be the result of increased TH activity and due to released DA from dopaminergic neurons.
    Keywords: Dopamine, L-DOPA, Mesenchymal stem cells, Parkinson's disease, Rat, Tyrosine hydroxylase
  • Rania Elgohary *, Rania Abdelsalam, Omar Abdel-Salam, Mahmoud Khattab, Neveen Salem, Zakaria El‐Khyat, Fatma Morsy Pages 1182-1189
    Objective(s)
    This study aimed to determine the impact of cannabinoid agonists and antagonists on the mucosal lesion progress in the stomach induced by water-immersion restraint stress (WIRS).   
    Materials and Methods
    Rats subjected to WIRS for 4 hr were treated with Dimethyl sulfoxide (DMSO), CBR1 agonist (NADA 1 mg/kg), CBR1 antagonist (Rimonabant 1 mg/kg), CBR2 agonist (GW405833 1 mg/kg) or CBR2 antagonist (AM630 1 mg/kg SC) 30 min before WIRS. Microscopic lesions, oxidative stress, inflammatory cytokines biomarkers, and (Myeloperoxidase) MPO in gastric tissues were determined.
    Results
    Results indicated development of severe gastric lesions with a substantial increase in the contents of (nitric oxide) NO, (malondialdehyde) MDA,  (interleukin-1 beta) IL-1β, MPO, (tumor necrosis factor-alpha) TNF-α, and a significant fall in the content of GSH and the activity of  PON-1 after WIRS.
    Conclusion
    Treatment with NADA and AM630 protected gastric tissues against ulcers as demonstrated by a decrease in the contents of MDA, TNF-α, MPO, and IL-1β along with an increase in the content of PON-1 activity and GSH in the stomach tissues. On the other hand, treatment with SR141716A or GW405833 showed no protective effects on ulcers development. It seems that cannabinoids exert their antioxidant potential and anti-inflammatory effects against  WIRS-induced gastric ulcers by activation of CB1R.
    Keywords: Anti-oxidant, Cannabinoid receptor, stress, TNF-α, Ulcer
  • Reza Jafarzadeh Esfehani, Atieh Eslahi, Mehran Beiraghi Toosi, Ariane Sadrnabavi, Mohammad Amin Kerachian, Mahsa Sadat Mohajeri Asl, Mahsa Farjami, Farzaneh Alizadeh, Majid Mojarad * Pages 1190-1195
    Objective(s)
    Infantile neuroaxonal degeneration (INAD) is a rare subgroup of neurodegeneration with brain iron accumulation (NBIA) disorders. This progressive disorder may develop during the early years of life. Affected individuals mostly manifest developmental delay and/or psychomotor regression as well as other neurological deficits. In the present study, we discussed 3 INAD patients diagnosed before the age of 10 by using Whole-Exome Sequencing (WES).
    Materials and Methods
    We evaluated 3 pediatric patients with clinical phenotypes of INAD who underwent WES. Sanger sequencing was performed for co-segregation analysis of the variants in the families. An in-silico study was conducted for identification of the molecular function of the identified genetic variants in the PLA2G6 gene.
    Results
    We detected three novel genetic variants in the PLA2G6 gene including a homozygous missense (NM_003560.2; c.1949T>C; p.Phe650Ser), a splicing (NM_001349864; c.1266-1G>A) and a frameshift variant (NM_003560.4; c.1547_1548dupCG; p.Gly517ArgfsTer29). Since the variants were not previously reported in literature or population databases, we performed in-silico studies for these variants and demonstrated their potential pathogenicity.
    Conclusion
    The current study reports novel genetic variants in the PLA2G6 gene in the Iranian population, emphasizing the importance of high-throughput genetic testing in rare diseases.
    Keywords: Developmental disabilities, magnetic resonance imaging, Neuroaxonal dystrophies, Pantothenate kinase associated neuro degeneration, Whole exome sequencing
  • Mohammad Mahdi Rafiei, Raheleh Soltani, Mohamadreza Kordi, Reza Nouri *, Abbasali Gaeini Pages 1196-1202
    Objective(s)
    Breast cancer is the most common cancer in women, caused by a disorder in the angiogenesis and apoptosis process. Exercise can affect the process of angiogenesis and apoptosis in the tumor tissue. Thus, the aim of the present study was to investigate the changes in angiogenesis and apoptotic factors in mice with breast cancer after 8 weeks of exercise training.
    Materials and Methods
    Sixteen females BALB/c mice (age: 3-5 weeks and weight: 17.1 ± 0.1 g) with breast cancer were randomly divided into two groups of aerobic training and control. The aerobic training included 8 weeks and 5 sessions per week of running with an intensity of 14-20 m.min-1. HIF-1α, VEGF, miR-21 and cytochrome C, Apaf-1, caspase-9, and caspase-3 gene expressions were examined by real-time PCR. Repeated measures ANOVA, Bonferroni’s post hoc test, and independent samples t-test were used to analyze the data (p <0.05).
    Results
    The results showed that aerobic training reduced the growth of tumor volume and significantly reduced miR-21 gene expression. Aerobic training also significantly increased the gene expression of HIF-1α, cytochrome C, Apaf-1, caspase-9, and caspase-3, while changes in VEGF gene expression were not statistically significant.
    Conclusion
    It appears that aerobic exercise training reduces tumor size and ameliorates breast cancer by reducing miR-21 gene expression, suppressing the apoptosis process, and reducing angiogenesis.
    Keywords: aerobic exercise, Angiogenesis, Apoptosis, Breast Cancer, Gene expression
  • Kalina Belemezova *, Ivan Bochev, Ekaterina Ivanova-Todorova, Stanimir Kyurkchiev, Dobroslav Kyurkchiev Pages 1203-1210
    Objective(s)
    Mesenchymal stem cells (MSCs) exist in almost all tissues. Their unique nature is completed by their immunomodulatory functions, holding promise for the treatment of many diseases. An inflammatory environment precedes the immunosuppressive abilities of MSCs and this study was intended to better understand how umbilical cord MSCs (UCMSCs) react to the process of inflammation, regarding their basic characteristics and behavior when primed with the key pro-inflammatory cytokine, Interferon-γ (IFNγ).
    Materials and Methods
    Human MSCs from the umbilical cord were isolated, expanded, and treated with IFNγ. Primed cells were analyzed to define their ability to form colonies, their morphology, differentiation potential, proliferation, and apoptosis rate.  
    Results
    UCMSCs treated with IFNγ changed their fibroblast-like morphology and retained the expression of typical MSCs markers. IFNγ treated UCMSCs had significantly higher MFI levels regarding the expression of HLA-I (980.43 ± 556.64) and PD-L1 (598.04 ± 416.90) compared with the control cells (144.97 ± 78.5 and 122.05 ± 103.83, respectively; p <0.01). Under the influence of IFNγ, the cells had a lower population doubling time compared with the control cultures (50.345 ± 9.155 versus 61.135 ± 21.110, respectively; p <0.01) and higher numbers of colony-forming unit-fibroblasts (26.0 ± 12.2 versus 10.2 ± 8.0, respectively; p <0.05). The primed MSCs could not undergo osteogenic and adipogenic differentiation. IFNγ increased the percentage of cells in the apoptotic state on day eight (29.470 ± 6.59 versus 15.708 ± 6.190, respectively; p <0.01).
    Conclusion
    The properties of UCMSCs can be influenced by the pro-inflammatory cytokine IFNγ.
    Keywords: Cytokine, Differentiation, Inflammation, PD-L1, Proliferation, Stem cells
  • Mahdie Koushki, Azam Khedri, Mohammad Aberomand, Kourosh Akbari Baghbani, Ghorban Mohammadzadeh * Pages 1211-1219
    Objective(s)
    Recently, there is a significant focus on combination chemotherapy for cancer using a cytotoxic drug and a phytochemical compound. We investigated the effect of silibinin on etoposide-induced apoptosis in MCF-7 and MDA-MB-231 breast carcinoma cell lines.
    Materials and Methods
    The cytotoxic effects of silibinin and etoposide were determined using MTT assay after 24 and 48 hr incubation with these drugs individually and combined. The mRNA expression of Bax and Bcl2, and protein levels of P53, phosphorylated p53 (P-P53), and P21 were determined using real-time PCR and western blot analysis, respectively. The caspase 9 activity was measured using an ELISA kit.
    Results
    Silibinin and etoposide alone and combined significantly inhibit cell growth in a dose and time-dependent manner in both cell lines. The strongest synergistic effects in terms of MCF-7 cell growth inhibition [combination index (CI) = 0.066] were evident. The silibinin-etoposide combinations cause a much powerful apoptotic death (47% and 40%) compared with each compound individually in MCF-7 and MDA-MB 231 cells, respectively. Additionally, the silibinin-etoposide combinations significantly increased the expression of P53, P-P53, and P21 in MCF-7 cells. Neither silibinin nor etoposide individually increased the level of P53 and P-P53 in MDA-MB-231 cells, but both of them individually and combined increased the level of P21.
    Conclusion
    Since the silibinin-etoposide combination induces apoptosis in both cell lines with and without expression of p53, thus, it is suggested that this combination may be a successful therapeutic strategy for breast cancer regardless of P53 status.
    Keywords: Apoptosis, Breast Cancer, Drug synergism, Etoposide, MCF-7 cells, Silibinin
  • Hengame Soudi *, Tahereh Falsafi, Mohaddeseh Mahboubi, Sara Gharavi Pages 1220-1230
    Objective(s)
    Outer inflammatory protein A (OipA) is an essential adhesin of Helicobacter pylori. We aimed to evaluate the effects of a recombinant OipA in the induction of crucial cytokines as a vaccine candidate and propolis as an adjuvant in C57BL/6 mice.
    Materials and Methods
    C57BL/6 mice were divided into nine groups according to the disposition of antigen and adjuvant and route of administration: subcutaneous (sc) or gavage. The administrated recombinant purified OipA and propolis concentrations were 10 μg/ml and 40 μg/ml, respectively. After vaccination, we measured expression levels of IFN-γ and IL-4 cytokine genes in the spleen cells of mice by real-time PCR.
    Results
    All results were contrasted with the negative sample. By sc injection, the expression of INF-γ was increased 3.5 and 2.9-fold for OipA and OipA plus propolis, respectively. By gavage 4.4 and 11-fold increase was found for OipA and OipA plus propolis, respectively. The administration of propolis by gavage showed more increase than Sc injection concerning the production of INF-γ. The 11-fold increase for injection of OipA plus propolis by gavage was comparable OipA plus Freund’s adjuvant injected subcutaneously. This result suggested an excellent immunological response toward OipA concerning the production of INF-γ in mice. In all cases there were no notable IL-4 production increases.
    Conclusion
    The results confirm the efficiency of OipA in induction of IFN-γ production, and thereby the cellular immune response. Propolis could be a suitable adjuvant.
    Keywords: Adjuvant, Helicobacter pylori, IFN-γ, IL-4, OipA, Propolis, Vaccine
  • Fatemeh Rafieenia, Elham Nikkhah, Fatemeh Nourmohammadi, Sousan Hosseini, Abbas Abdollahi, Nourieh Sharifi, Mohsen Aliakbarian, Mohammad Mahdi Forghani Fard, Mehran Gholamin, Mohammad Reza Abbaszadegan * Pages 1231-1239
    Objective(s)
    Besides the uncertainty about colorectal cancer stem cell (CCSC) markers, isolating, purifying, and enriching CCSCs to produce CCSC vaccines is highly challenging. However, allogeneic vaccines developed from CRC cell lines can provide universal, comprehensive, inexpensive, simple, and fast approach to cancer treatment.
    Materials and Methods
    CCSCs were isolated from human CRC tissue using the in vitro sphere formation assay and then characterized through gene expression analysis, in vivo and in vitro tumor formation assay, karyotyping, and surface marker detection. Subsequently, CCSCs and two CRC cell lines (HT-29 and SW-480) were inactivated with cisplatin (CDDP) and administrated as vaccines to the three groups of athymic C57BL/6 nude mice. Afterward, tumorigenesis was challenged with HT-29 cells. The antitumor effect of vaccines was evaluated by tumor and spleen examination and immune response analysis. The cytotoxic activity of splenocytes and serum levels of TGF-β and IFN-γ were measured by Calcein-AM cytotoxicity assay and enzyme-linked immunosorbent assay (ELISA), respectively.
    Results
    The results of gene expression analysis showed that CCSCs are CD44+CD133-LGR5-. All vaccinations resulted in decreased tumor growth, spleen enlargement, enhanced serum level of IFN-γ and TGF-β, and increased cytotoxic activity of natural killer (NK) cells. The antitumor efficacy of the CCSC vaccine was not more than CRC cell line-based vaccines. Interestingly, the allogeneic SW-480 vaccine could effectively inhibit tumorigenesis.
    Conclusion
    Despite the great challenge in developing CCSC vaccines, allogeneic vaccines based on CRC cell lines can efficiently induce antitumor immunity in CRC.
    Keywords: Allogeneic, Autologous, Cancer Stem cell, Colorectal cancer, Vaccine
  • Seyed Jalal Hosseinimehr, Soghra Farzipour, Maryam Alvandi, Zahra Shaghaghi * Pages 1240-1246
    Objective(s)
    Lung cancer is the main cause of cancer death, and its incidence is increasing worldwide. The goal of this study is to evaluate in vitro and in vivo tumor targeting behavior of [99mTc]Tc -HYNIC-(Ser)3-J18 in lung carcinoma (SK-MES-1)-bearing mice.
    Materials and Methods
    The J18 (RSLWSDFYASASRGP) peptide was conjugated with hydrazinonicotinamide (HYNIC) via three serine amino acids as a linker at the peptide’s N-terminal and then labeled with technetium-99m using tricine and tricine/EDDA as the co-ligands. The radiolabeled peptides were assessed for in vitro receptor binding, specific binding, and saturation affinity. In vivo biodistribution studies were also performed for 99mTc-peptide 1 (tricine co-ligand) and 99mTc-peptide 2 (tricine/EDDA coligands) in nude mice bearing SK-MES-1 xenograft tumors.
    Results
    In vitro studies showed high specific binding for 99mTc-peptide 1 in SKMES-1 cells compared with 99mTc-peptide 2 (11.5 vs. 4.5). The Kd values for 99mTc-peptide 1 and 99mTc-peptide 2 were reported to be 3.1±0.3 nM and 3.46 ± 0.8 nM, respectively.  The biodistribution study also showed high significant tumor to muscle ratios were 5.1 and 6.18 for 99mTc-peptide 1 at 1 and 2 hr after injection, respectively, while these ratios were 3.81 and 5.18 for peptide 2, respectively.
    Conclusion
    Overall, 99mTc-labeled J18 peptide in the presence of tricine as co-ligand has better in vitro and in vivo tumor targeting properties in SK-MES-1 cells than tricine/EDDA co-ligands. These findings show that the 99mTc-labeled J18 peptide is a good candidate for lung carcinoma targeting.
    Keywords: [99mTc ]Tc-HYNIC-(Ser)3-J18, EDDA, HYNIC-SSS-J18, Linker, Lung carcinoma targeting, NSCLC, Tricine
  • Xi Jiang *, Ying Hu, Yingjie Zhou, Jin Chen, Chonglu Sun, Ziwei Chen, Changfeng Jing, Lexing Xu, Fuhe Liu, Wenjuan Ni, Xuefeng Yu, Lei Chen Pages 1247-1253
    Objective(s)
    This research was designed to determine the role of irisin in lipopolysaccharide (LPS)-induced endometritis in female mice.
    Materials and Methods
    Animals were randomly assigned into sham, sham + irisin, LPS, LPS + irisin (0.1, 1, 10 μg/kg), and LPS + irisin + compound C groups. Histological features and expression of AMPK, NF-κB, inflammatory mediators, and oxidative stress markers were compared among different groups.
    Results
    The results showed that LPS resulted in obvious uterus damage, meanwhile, the inflammatory mediators (COX-2, iNOS, IL-1β, IL-6, and TNF-α), as well as NF-κB in the uterine tissue, were significantly increased and the level of adenosine monophosphate-activated protein kinase (AMPK) was reduced. Nevertheless, pretreatment with irisin reversed the phenomena caused by LPS. Interestingly, compound C (AMPK inhibitor) abolished irisin’s effects on the uterus, which suggested that irisin’s beneficial function was achieved through regulating the AMPK-NF-κB pathway. Moreover, LPS-induced alterations of oxidative factors (MnSOD, GSH, and MDA) were reversed significantly by pretreatment with irisin. This data indicated irisin’s beneficial function was also related to antioxidation besides anti-inflammation.  
    Conclusion
    Our study implies that irisin is a potential therapeutic agent for endometritis.
    Keywords: AMP-activated protein kinases, Endometritis, Inflammation, Irisin, Lipopolysaccharide NF-κB
  • Ladan Rahimzadeh Torabi, Monir Doudi *, Nafiseh Sadat Naghavi, Ramesh Monajemi Pages 1254-1263
    Objective(s)
    With emergence of drug resistance, novel approaches such as phage therapy for treatment of bacterial infections have received significant attention. The purpose of this study was to isolate and identify effective bacteriophages on extremely drug-resistant (XDR) bacteria isolated from burn wounds.
    Materials and Methods
    Pathogenic bacteria were isolated from hospitalized patient wounds in specialized burn hospitals in Iran, and their identification was performed based on biochemical testing and sequencing of the gene encoding 16S rRNA. Bacteriophages were isolated from municipal sewage, Isfahan, Iran. The phage morphology was observed by TEM. After detection of the host range, adsorption rate, and one-step growth curve, the phage proteomics pattern and restriction enzyme digestion pattern were analyzed.
    Results
    All isolates of bacteria were highly resistant to antibiotics. Among isolates, Acinetobacter baumannii strain IAU_FAL101 (GenBank accession number: MW845680), which was an XDR bacterium, showed significant sensitivity to phage Pɸ-Bw-Ab. TEM determined the phage belongs to Siphoviridae. They had double-stranded DNA. This phage showed the highest antibacterial effect at 15 °C and pH 7. Analysis of the restriction enzyme digestion pattern showed Pɸ-Bw-Ab phage was sensitive to most of the used enzymes and based on SDS-PAGE, protein profiles were revealed 43 to 90 kDa.
    Conclusion
    Considering the potential ability of the isolated phage, it had an antibacterial impact on other used bacterial spp and also strong antibacterial effects on XDR A. baumannii. Also, it had long latency and low burst size. This phage can be a suitable candidate for phage therapy.
    Keywords: Acinetobacter baumannii, Bacteriophage, Burns, Drug resistance, Lambda-Like Phage, Restriction Enzyme-Mapping, Sodium Dodecyl Sulfate-PAGE, Wound infections
  • Nazli Sotoudeh, Zahra Noormohammadi, Mahdi Habibi-Anbouhi, Fatemeh Kazemi-Lomedasht, Mahdi Behdani * Pages 1264-1271
    Objective(s)
    Cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) is the most important human immune checkpoint that modulates T cells activity and brings about immune-homeostasis. Accordingly, checkpoint inhibitor cancer therapy has been approved as a growing method to block over-expressed immune checkpoints, such as CTLA-4 receptors. Considering the competitive characteristics of single-domain antibodies with monoclonal antibodies, we tried to develop a camelid Nanobody against human CTLA-4.
    Materials and Methods
    We have constructed the VHH gene library by using immunized-camel peripheral blood mononuclear cells and carrying out the Nested-PCR technique. VHH-library was screened by phage display technique and specific nanobodies against CTLA-4 protein were selected and amplified with bio-panning steps. Stronger binders were screened by Periplasmic Extract-ELISA, followed by estimating the complexity of the library. Specific anti-CTLA-4 Nanobody and 3hCTL55, with longer CDR3 and a higher binding rate, were selected for more assays.
    Results
    Results revealed the existence of two different clones in the library with 108 binders. In comparison with seven different antigens, using the ELISA technique confirmed the specificity of Nanobody 3hCTL55 against human CTLA-4 antigen. We calculated Nanobody 3hCTL55 affinity for human CTLA-4 antigen at 50×10-9 M, approximately. Performing western blot and Flow-cytometry techniques showed that Nanobody 3hCTL55 was able to specifically detect and attach both commercial human CTLA-4 protein and human CTLA-4 antigen on the cell surface and in the cell lysate.
    Conclusion
    Taken together, this developed camelid-specific anti-CTLA-4 Nanobody 3hCTL55, selected from a high-quality immune library by phage display technique, may be effective for further study about cancer diagnosis and cancer-therapy purposes.
    Keywords: CTLA-4 antigen, Immune checkpoint- proteins, Immunotherapy, Nanobody, Single-domain antibodies
  • Jieting Kong, Shengli Gao, Xiaoman He, Nana Zhang, Jinfang Huang, Pengfei Ji, Shouheng Yao, Xiang Ren, Yiru Wang, Yanling Gong, Feifei Guo * Pages 1272-1278
    Objective(s)
    To investigate the regulatory effects of the nucleus accumbens (NAcSh)-lateral hypothalamus (LHA) GABAergic neural pathway on palatable food (PF) intake via orexin-A expression in diet-induced obesity (DIO) rats.
    Materials and Methods
    NAcSh-LHA GABAergic pathways were observed by fluorogold retrograde tracing combined with fluorescence immunohistochemistry, and the regulatory effects of this neural pathway on PF intake were detected after 1) microinjection of GABA-A receptor agonist muscimol (MUS) or antagonist bicuculine (BIC) into LHA, 2) electrical stimulation NAcSh, and 3) blocking the orexin-A receptor by icv SB334867.
    Results
    Compared with rats on a normal diet (ND), NAcSh-LHA GABAergic neurons in the DIO rats were significantly decreased, and orexin-A expression in LHA significantly increased (p <0.05). Microinjection of MUS into LHA significantly decreased the PF intake in both ND and DIO rats (p <0.05), and BIC could markedly increase the PF intake in the ND rats (p <0.05), but not the DIO rats (P>0.05). After NAcSh electrical stimulation or SB334867 ICV injection, the PF intake was significantly decreased in the DIO rats (p <0.05), and there was no significant difference after preadministration of BIC into LHA (P>0.05).
    Conclusion
    This GABAergic pathway could regulate the expression of orexin-A in LHA and PF intake. Orexin-A neurons in LHA of DIO rats might be less sensitive to GABAergic signals and may consequently lead to more hedonic food intake.
    Keywords: Food intake, GABA, Nucleus accumbens, Obesity, Orexin-A
  • Sasan Zaeri *, Fatemeh Karami, Majid Assadi Pages 1279-1291
    Objective(s)
    The wound healing potential of beta-blocker drugs such as propranolol (PNL) has recently attracted attention. To date, incorporation of PNL into electrospun nanofibrous wound dressing mats has not been tested as a novel topical drug delivery system. Presently, electrospun nanofibrous mats loaded with PNL were fabricated, and their physicochemical properties and wound healing activities were evaluated.
    Materials and Methods
    Polyvinyl alcohol solutions containing 0, 2% or 4% (wt/vol) PNL were electrospun into mats, and the physicochemical properties and PNL release were evaluated. In vitro biocompatibility of selected PNL-loaded mats was tested in human foreskin fibroblasts and wound healing capability was evaluated in mouse skin wounds.
    Results
    The 4% PNL mat had thin fibers (160 nm), convincing porosity (79.5%), and good hydrophilicity (swelling: 89.1%, water contact angle: 42.1°) with little degradability (14.2%). The release of PNL was not in bursts and was best explained by the Korsmeyer–Peppas equation (R2 = 0.96, n = 0.40), suggesting Fickian release. The viability of fibroblasts was 173% on day 5 of incubation with 4% PNL mats, indicating good mat biocompatibility. In vivo treatment for 14 days with 4% PNL mats resulted in wounds with a surface area of only 9% of the original wound area. These wounds had better histopathologic characteristics and were associated with less oxidative stress.
    Conclusion
    The wound dressing fabricated with 4% PNL showed good potential for wound healing because of a favorable drug release profile from the nanofiber scaffold, and can be considered eligible for further clinical research.
    Keywords: Electrospun nanofiber, Fibroblast, Mouse, Oxidative stress, Propranolol, Wound
  • Elham Nikkhah, Fatemeh Kalalinia, Mitra Asgharian Rezaee, Zahra Tayarani-Najaran * Pages 1292-1300
    Objective(s)
    Mesenchymal stem cells (MSCs) extensively interact with cancer cells and other stromal cells in the tumor microenvironment. However, the role of MSCs in colorectal cancer (CRC) development and metastasis is controversial. Strong evidence demonstrated that conditioned medium (CM) obtained from MSCs regulates main cellular functions such as proliferation, differentiation, migration, and communication due to its cell secretomes. This study was designed to determine the inhibitory effect of dental pulp stem cells (DPSC) and its extracted conditioned medium (DPSC-CM) in CRC progression.
    Materials and Methods
    The inhibitory effects of DPSC-CM on growth, apoptosis, and migration of CRC cells were evaluated by resazurin, flow cytometry of propidium iodide (PI) stained cells, and wound closure assay, respectively. Western blotting detected the expression of MAPKinase and apoptotic proteins. Also, the homing ability of DPSCs and the invasion ability of CRC cells under indirect co-culture were assayed by the Boyden chamber assay.            
    Results
    DPSC-CM reduced the viability and induced the apoptosis of CRC cells significantly. Western blot analysis confirmed the increase in cytochrome C, phospho-JNK/SAPK to JNK/SAPK ratio, cleaved-caspase 8 and 3 in treated CRC cells with DPSC-CM, and decrease in phospho-ERK (P44/42 MAPK) to ERK (P44/42 MAPK) ratio, which are involved in induction of apoptosis and growth inhibition of cancer cells with minimal change in normal cells. Also, DPSCs could migrate (homing ability) to Caco2 and SW48 cells significantly.
    Conclusion
    To sum up, DPSC-CM had significant apoptotic and growth inhibitory effects on the CRC cells through the MAPKinase and apoptosis signaling pathways.
    Keywords: Apoptosis, Colonic neoplasms, Conditioned medium, Dental pulp, MAP kinase cascade, Stem cells
  • Esra Guzel Tanoglu * Pages 1301-1306
    Objective(s)

    This study aimed to research the roles of miR-139, miR-221, miR-200c, miR-145, miR-223, miR-424, and miR-377 in endoplasmic reticulum stress (ERS), oxidative stress (OS), fibrosis, and apoptosis processes in chronic pancreatitis (CP) rat model.

    Materials and Methods

    Fourteen rats were randomized into 2 groups (Group 1, sham group (n=7) and Group 2, CP group (n=7)). TGF-beta and malondialdehyde concentrations were measured in rat blood samples. qRT-PCR was used to investigate the expression levels of 7 miRNAs in the pancreas tissues. The correlations of mRNA undergoing significant changes with inflammation (TNF-α, IL-6), ERS (Ire1-α, Perk), apoptosis (Caspase 3, Bcl-2), OS (Cat, Gpx1), and fibrosis (α-Sma) were investigated.

    Results

    The biochemical results and histopathological scores in Group 1 were statistically significantly high compared with Group 2 (p <0.5). Expression levels of seven miRNAs (miR-200c, miR-145, miR-223, miR-424) were significantly higher, while miR-139 was significantly lower in CP. In our study, we found that miR-200c, miR-145, and miR-139 may contribute to CP progression and cellular processes based on the correlation between ERS, OS, apoptosis, and inflammation with miRNA expression levels.

    Conclusion

    miR-200c, miR-145, miR-139, miR-223, and miR-424 play roles in the CP model. They may be used as candidate biomarkers for the CP process.

    Keywords: Apoptosis, Chronic Pancreatitis, microRNAs, Oxidative stress, Quantitative real-time polymerase chain reaction, Rat