2024-03-28T16:33:02Z
https://ijbms.mums.ac.ir/?_action=export&rf=summon&issue=1965
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
2
Alzheimer’s disease treatment: The share of herbal medicines
Masoud
Soheili
Mohammad
Karimian
Gholamali
Hamidi
Mahmoud
Salami
One of the most frequent forms of dementia in neurological disorders is Alzheimer’s disease (AD). It is a chronic neurodegenerative disease characterized by impaired learning and memory. Pathological symptoms as extracellular amyloid-beta (Aβ) plaques and intracellular accumulation of neurofibrillary tangles occur in AD. Due to the aging of the population and increased prevalence of AD, discovery of new therapeutic agents with the highest effectiveness and fewer side effect seems to be necessary. Numerous synthetic medicines such as tacrine, donepezil, galantamine, rivastigmine, memantine, glutathione, ascorbic acid, ubiquinone, ibuprofen, and ladostigil are routinely used for reduction of the symptoms and prevention of disease progression. Nowadays, herbal medicines have attracted popular attention for numerous beneficial effects with little side effects. Lavandula angustifolia, Ginkgo biloba, Melissa officinalis, Crocus sativus, Ginseng, Salvia miltiorrhiza, and Magnolia officinalis have been widely used for relief of symptoms of some neurological disorders. This paper reviews the therapeutic effects of phytomedicines with prominent effects against various factors implicated in the emergence and progression of AD.
Alzheimer’s disease
Crocus sativus
Ginkgo biloba
Ginseng
Lavandula angustifolia
Magnolia officinalis
Melissa officinalis
Salvia miltiorrhiza
2021
02
01
123
135
https://ijbms.mums.ac.ir/article_17118_63c274e2ddc401a3f0132c1545849a93.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
2
Integron and its role in antimicrobial resistance: A literature review on some bacterial pathogens
Parisa
Sabbagh
Mehdi
Rajabnia
AMirhosein
Maali
Elaheh
Ferdosi-Shahandashti
In recent years, different acquired resistance mechanisms, including transposons, bacteriophages, plasmids, and integrons have been identified as involved in the spread of resistance genes in bacteria. The role of integrons as mobile genetic elements playing a central role in antibiotic resistance has been well studied and documented. Integrons are the ancient structures that mediate the evolution of bacteria by acquiring, storing, disposing, and resorting to the reading frameworks in gene cassettes. The term integron describes a large family of genetic elements, all of which are able to capture gene cassettes. Integrons were classified into three important classes based on integrase intI gene sequence. Integrons can carry and spread the antibiotic resistance genes among bacteria and are among the most significant routes of distribution of resistance genes via horizontal transfer. All integrons have three essential core features. The first feature is intI, the second one is an integron-associated recombination site, attI, and an integron-associated promoter, Pc, is the last feature. Among them, the class 1 integron is a major player in the dissemination of antibiotic resistance genes across pathogens and commensals. Various classes of integrons possessing a wide variety of gene cassettes are distributed in bacteria throughout the world. This review thus focuses on the distribution of integrons among important bacteria.
Antibiotic resistance
Gene cassettes
Integrases
Integrons
Mobile elements
2021
02
01
136
142
https://ijbms.mums.ac.ir/article_17187_90040334894577bf4b6d8a3992b9ab69.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
2
Interference of Lactobacillus casei with Pseudomonas aeruginosa in the treatment of infected burns in Wistar rats
Mohammad
Abootaleb
Narjes
Mohammadi Bandari
Nazila
Arbab Soleimani
Objective(s): Burns are the most common type of trauma with a high mortality rate worldwide. The use of modern and natural medicines, especially probiotic products, has been recently considered for cutaneous wound healing. The present study was designed to investigate the effect of Lactobacillus casei on wound healing caused by Pseudomonas aeruginosa. Materials and Methods: In this study, the anti-adhesion activity of L. casei was examined by the glass slide method, and inhibitory substances in the cell-free supernatant (CFS) were quantified by high-performance liquid chromatography (HPLC). Following the induction of second-degree wounds, multidrug-resistant (MDR) P. aeruginosa was injected subcutaneously and directly on the burn. The animals were divided into four groups. The supernatant of L. casei was sprayed for treatment every day and wound healing was examined. Results: Based on our findings, the supernatant of L. casei showed considerable anti-adhesion effects on P. aeruginosa. HPLC analysis indicated that the inhibitory effect of this supernatant can be due to four main organic acids including lactic acid, acetic acid, citric acid, and succinic acid. The effect of treatment on fibroblastic cells showed that the treated group by supernatant of L. casei had more fibroblastic cells compared with the non-treated group. Moreover, this supernatant increased the rate of fibroblastic cells, re-epithelialization in the wound area, and the largest thickness of the epidermis and dermis layers.Conclusion: The present findings showed that L. casei supernatant significantly reduced inflammation and could be used to treat P. aeruginosa infection in second-degree burns.
Biofilms Multidrug
resistant Probiotics Pseudomonas infections Wound healing
2021
02
01
143
149
https://ijbms.mums.ac.ir/article_17311_309d00a725059d3b145b36ee53300c15.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
2
Exercise alleviates cardiac remodelling in diabetic cardiomyopathy via the miR-486a-5p-Mst1 pathway
Dong
Sun
Haichang
Wang
Yanhui
Su
Jie
Lin
Mingming
Zhang
Wanrong
Man
Xinglong
Song
Liang
Zhang
Baolin
Guo
Kaikai
Hao
Dongdong
Sun
Objective(s): Physical exercise has emerged as an effective therapy to mitigate cardiac remodelling in diabetic cardiomyopathy (DCM). The results of our previous studies revealed mammalian sterile 20-like kinase 1 (Mst1) is a key regulator of the progression of DCM. However, the precise molecular mechanism of physical exercise-induced cardiac protection and its association with Mst1 inhibition remain unclear. Materials and Methods: Wildtype and Mst1 transgenic mice were challenged with streptozotocin (STZ) to induce experimental diabetes and were divided into sedentary and exercise groups. The DCM phenotype was evaluated by echocardiography, Masson’s trichrome staining, TUNEL and immunoblotting analyses. The exercise-regulated miRNAs targeting Mst1 were predicted by bioinformatic analysis and later confirmed by RT-qPCR, immunoblotting, and dual-luciferase reporter assays. In addition, cultured neonatal mouse cardiomyocytes were subjected to simulate diabetes to elucidate the underlying mechanisms. Results: Compared to the sedentary diabetic control, physical exercise inhibited Mst1 and alleviated cardiac remodelling in mice with DCM, as evidenced by decreases in the left ventricular end-systolic internal dimension (LVESD) and left ventricular end-diastolic internal dimension (LVEDD), increases in the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), attenuation of collagen deposition, and the suppression of apoptosis. Bioinformatic analysis and apoptosis assessments revealed exercise exerted protective effects against DCM through miR-486a-5p release. Moreover, luciferase reporter assays confirmed miR-486a-5p directly suppressed the expression of Mst1, thereby inhibiting the apoptosis of cardiomyocytes subjected to high glucose treatment. Conclusion: Physical exercise inhibits cardiac remodelling in DCM, and the mechanism is associated with miR-486a-5p release-induced Mst1 inhibition.
Apoptosis Diabetic cardiomyopathy Exercise Mst1 (STK4) miR
486a
5p
2021
02
01
150
159
https://ijbms.mums.ac.ir/article_17312_02215c54ec3607a8133245b1777cd947.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
2
Cyanocobalamin improves memory impairment via inhibition of necrosis and apoptosis of hippocampal cell death after transient global ischemia/reperfusion
Hossein
Khastar
Behzad
Garmabi
Fatemeh
Zare Mehrjerdi
Mohamad Taghi
Rahimi
Nabi
Shamsaei
Amir-Hossein
Ali
Nilofar
Khorsand
Mehdi
Khaksari
Objective(s): Brain ischemia/reperfusion (I/R) causes irreversible damage, particularly in the hippocampus. Cyanocobalamin (CNCbl) is known to be crucial for the proper operation of the nervous system. Vitamin B12 has been demonstrated to exert antioxidant effects via direct and indirect mechanisms. It can also protect cortical neurons against glutamate cytotoxicity. This research was conducted to examine CNCbl protection against neuronal cell death in the rat hippocampal region following transient cerebral ischemia.Materials and Methods: In this experiment, 48 male Wistar rats were selected, which were randomly divided into four groups (n=12 in each group): sham, ischemia/reperfusion, ischemia/reperfusion + CNCbl 200 and 400 (µg/kg). By occlusion of both common carotids, ischemia induction was performed within 20 min. CNCbl at the doses of 200 and 400 µg/kg was injected (IP) at the start of the reperfusion, 24 and 48 hr following reperfusion. The spatial memory was assessed 7 days following ischemia through the Morris water maze test. Antioxidant enzymes, apoptosis, and necrosis were measured after behavioral tests. Results: CNCbl significantly improved spatial memory impairments (p <0.05), also CNCbl therapy significantly increased both glutathione (p <0.01) and superoxide dismutase (p <0.05) and reduced malondialdehyde (p <0.01) and TNF-α (p <0.05) in comparison with the ischemia group. In addition, CNCbl significantly decreased both apoptosis and necrosis in the hippocampus CA1 (p <0.01).Conclusion: CNCbl improves memory impairment following ischemia injury by decreasing neuronal cell death via its antioxidant properties.
Apoptosis
Brain ischemia
Cyanocobalamin
Hippocampus
Memory
Necrosis
2021
02
01
160
166
https://ijbms.mums.ac.ir/article_17314_48f266ea9efe6f13a36b50bfa654085a.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
2
The combination of vitamin D3 and erythropoietin alleviates acute kidney injury induced by ischemia-reperfusion via inhibiting inflammation and apoptosis
Longyan
Qin
Xin
Lin
Juan
Liu
Rong
Dong
Jing
Yuan
Yan
Zha
Objective(s): Acute renal ischemia may cause acute renal dysfunction due to lack of blood supply; the manifestations are renal tubular cell apoptosis, infiltration of macrophages, and microvascular destruction. Many studies have shown that erythropoietin (EPO) and vitamin D3 (VD3) can be used to prevent or treat renal ischemia-reperfusion (I/R) injury, and VD3 may interact with EPO. In the present study, the effects of the combination of VD3 and EPO in I/R acute kidney injury were studied. Materials and Methods: Rats were divided into 5 groups: sham-operated (SHAM), AKI without treatment (AKI-control), AKI treatment with VD3(AKI+VD3), AKI treatment with EPO(AKI+EPO), AKI treatment with VD3 and EPO(AKI+VD3+EPO). The effects of the combination of VD3 and EPO on AKI were assessed by histologic, inflammation, and apoptosis studies.Results: The degree of damage in renal tissue was significantly reduced in VD3, EPO, and combined groups. Combination therapy with VD3 and EPO markedly improved Creatinine clearance rate (CCr). The combined treatment group showed the lowest F4/80+ and CD68+ expressions. The expression of Bcl-2 in the combined treatment group was higher than those in VD3 group and the EPO group, while Bax’s expression goes in the opposite direction.Conclusion: This provides further evidence that VD3 and EPO have beneficial effects in I/R injury via anti-inflammatory and anti-apoptosis pathways. The synergistic protective effect of VD3 and EPO is of profound significance in the development of new strategies for the prevention and treatment of acute kidney injury (AKI).
Acute kidney injury
Apoptosis
Cholecalciferol
Erythropoietin
Inflammation
Vitamin D3
2021
02
01
167
174
https://ijbms.mums.ac.ir/article_17313_1bedf5cf22737a37e69b69e6d406a4d7.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
2
Comparative study of gavage and intraperitoneal administration of gamma-oryzanol in alleviation/attenuation in a rat animal model of renal ischemia/reperfusion-induced injury
Yasin
Bagheri
Alireza
Barati
Sana
Nouraei
Nasim
Jalili Namini
Mohammad
Bakhshi
Ezzatollah
Fathi
Soheila
Montazersaheb
Objective(s): Ischemia/reperfusion (I/R) is the leading cause of acute kidney injury. This study aimed to elucidate the reno-protective effect of gamma-oryzanol (GO) by comparing gavage and intraperitoneal (IP) administration methods on renal I/R injury in a rat model. Materials and Methods: Rats were divided into four groups including (group 1) sham, (group 2) I/R-control, (group 3) I/R+GO gavage-treated, and (group 4) I/R+ GO IP-treated. A single dose of GO was administrated to groups 3 and 4 (100 mg/kg body weight), 60 min before induction of I/R. After anesthesia, I/R was created by 45 min of ischemia, followed by 6 hr of reperfusion. Then, blood and tissue samples were subjected to evaluation of renal function, anti-oxidant capacity, inflammation, apoptotic proteins, and IKB/NF-kB pathway.Results: The two GO administration methods showed improvement of renal function along with attenuation of histological abnormalities. An increase in antioxidant capacity along with a decrease in pro-inflammatory markers, decline in the expression levels of BAX, Bax/Bcl-2, and caspase-3, and up-regulation of Bcl-2 expression were recorded. Moreover, a significant decrease in NF-Kb, p-IKBα, and MMP-2/9 with an increase in IKBα levels were also observed. Overall, in a comparative evaluation between the two gavage and IP administration methods, we did not find any differences in all examined parameters, except IL-6 which had a better result via gavage.Conclusion: A single dose of GO administration has a reno-protective effect against renal I/R injury. Gavage and IP administration exhibit similar efficiency in alleviation of I/R injury.
Anti
oxidants Gamma
oryzanol Gavage Intraperitoneal Renal ischemia/reperfusion Signaling pathways
2021
02
01
175
183
https://ijbms.mums.ac.ir/article_17220_b416dc5390316d19883e8be8526aa5d0.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
2
L-Carnitine ameliorates the liver by regulating alpha-SMA, iNOS, HSP90, HIF-1alpha, and RIP1 expressions of CCL4-toxic rats
Derya
Karabulut
Ali
Akin
Murat
Unsal
Ayça
Lekesizcan
Tuğçe
Ozyazgan
Didem
Keti
Birkan
Yakan
Görkem
Ekebas
Objective(s): Carbon tetrachloride (CCL4) toxicity triggers fibrosis, activating various mechanisms within the cell. We aimed to create damage with CCL4 and investigate the effectiveness of L-carnitine on the mechanisms we identified.Materials and Methods: Forty rats were divided into 5 groups with equal number of rats in each group. Group I: Control group, Group II: L-carnitine group, 200 mg/kg L-carnitine twice a week, Group III: CCL4 group, 0.2 ml/100 gr CCL4, IP, dissolved in olive oil 2 times a week during 6 weeks; Group IV: L-carnitine + CCL4 group, 200 mg/kg L-carnitine 24 hr before 0.2 ml/100 g CCL4 application twice a week; Group V: CCL4 + L-carnitine, 200 mg/kg L-carnitine half an hour after 0.2 ml/100 g CCL4 application. The liver was evaluated histologically. Immunohistochemically stained with α-SMA, iNOS, HSP90, HIF-1α, and RIP1. TNF-α, TGF-β, AST, ALT, ALP, and GGT measurements were evaluated. Results: In the classical lobule periphery, an increase in lipid accumulation and a decrease in glycogen accumulation were observed. After immunohistochemical measurements and biochemical analyzes, an increase in the expression density of all proteins was observed in group III. In group IV and V, an improvement in tissue and a decrease in protein expression densities were observed.Conclusion: iNOS serves as a free radical scavenger in response to damage caused by increased toxicity of α-SMA, HSP90, and HIF-1α. Especially, increased RIP1 level in the tissue indicates the presence of necrosis in the tissue after CCL4-toxicity. Supplementing the amount of endogenous L-carnitine with supplementation provides a significant improvement in the tissue.
Alpha
SMA CCL4 HIF
1alpha HSP90 iNOS RIP1
2021
02
01
184
190
https://ijbms.mums.ac.ir/article_17191_923610920c13d99a549b6154823b5d8f.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
2
Identification of a novel homozygous mutation in the DDR2 gene from a patient with spondylo-meta-epiphyseal dysplasia by whole exome sequencing
Masoud
Heidari
Morteza
Soleyman-Nejad
Alireza
Isazadeh
Mohammad Hossein
Taskiri
Manzar
Bolhassani
Nahid
Sadighi
Zahra
Shiri
Zahra
Karimi
Mansour
Heidari
Objective(s): The spondylo-meta-epiphyseal dysplasia (SMED) short limbs-hand type is a rare autosomal recessive disease, which is characterized by premature calcification leading to severe disproportionate short stature and various skeletal changes. Defective function of a conserved region encoding discoidin domain receptor tyrosine kinase 2 (DDR2 protein) by the discoidin domain-containing receptor 2 (DDR2 gene) is cause of this disease. The purpose of present study was to investigate disease-causing mutations on DDR2 gene in an Iranian family with SMED, and predict the DDR2 protein molecular mechanism in development of SMED.Materials and Methods: In the present study, we evaluated a 2-year-old male with SMED. Detection of genetic changes in the studied patient was performed using Whole-Exome Sequencing (WES). PCR direct sequencing was performed for analysis of co-segregation of variants with the disease in family. Finally, in silico study was performed for further identification of molecular function of the identified genetic variant.Results: We detected a novel splice-site mutation (NM_001014796: exon9: c.855+1G>A; NM_006182: exon8: c.855+1G>A) in DDR2 gene of the studied patient using WES. This mutation was exclusively detected in patients with homozygous SMED, not in healthy people. The effects of detected mutation on functions of DDR2 protein was predicted using in silico study.Conclusion: The causative mutation in studied patient with SMED was identified using Next-generation sequencing (NGS), successfully. The identified novel mutation in DDR2 gene can be useful in prenatal diagnosis (PND) of SMED, preimplantation genetic diagnosis (PGD), and genetic counseling.
DDR2 gene In silico Sanger sequencing Splice
site mutation Spondylo
meta
epiphyseal dysplasia Whole exome sequencing
2021
02
01
191
195
https://ijbms.mums.ac.ir/article_17190_92eab85991367fe107bd9942fc5bb248.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
2
LILRA3 is related to monocyte-derived dendritic cell maturation and activation
Xinyu
Wu
Qi
Cheng
Huawei
Jiang
Meiju
Zhou
Xiaochan
Chen
Huaxiang
Wu
Jing
Xue
Yan
Du
Objective(s): Previously we reported functional leukocyte immunoglobulin-like receptor A3 (LILRA3) leads to susceptibility and sub-phenotypes of several autoimmune diseases. LILRA3 levels in blood serum and CD14+ monocytes enhanced in systemic lupus erythematosus and resulted in disease severity. However, the mechanism of LILRA3 in the pathogenesis of autoimmunity remains elusive. This study aims to explore the potential impact of LILRA3 on the differentiation, maturation, and function of monocyte-derived DCs (MoDCs).Materials and Methods: The human monocytic cell line (THP-1) was cultured to derive MoDCs in vitro. We performed plasmid transfection to examine the impact of LILRA3 on monocyte differentiation. Surface markers on MoDCs were measured using FACS. To assess the function of mature MoDCs, IL-12p70, IFN-γ and IL-4 levels were detected after the mixed leucocyte response by enzyme-linked immunosorbent assay. Western blot assay was employed in this study to determine the signaling pathways in MoDCs activation.Results: LILRA3 promotes MoDCs maturation, our results showed significant up-regulation of CD40, CD80, CD86, CD209, and HLA-DR and increased production of pro-inflammatory cytokine IL-12. LILRA3-treated MoDCs exhibited a robust proliferation of allogeneic CD4+ T cells and induced naïve CD4+ T cell polarization into the Th1 phenotype. Furthermore, the preceding activation of MoDCs maturation and LILRA3 function might be attributed to p38 MAPK and STAT1 signaling pathway’s aberrant activation. Conclusion: This is the first study to report that LILRA3 played a critical role in promoting MoDCs maturation and directing MoDCs to modulate Th1 cell differentiation, which may have a role in the pathogenesis of autoimmune diseases.
Cell differentiation
Dendritic cell
JAK/STAT1
LILRA3
Monocyte
MAPK p38
2021
02
01
196
202
https://ijbms.mums.ac.ir/article_17134_c9baaeba60b75b9eb7ba79f2558ab915.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
2
Preparation and immunological properties of a nanovaccine against Pseudomonas aeruginosa based on gold nanoparticles and detoxified lipopolysaccharide
Faezeh
Najafzadeh
Asghar
Tanomand
Azam
Haddadi
Jafar
Majidi
Objective(s): Pseudomonas aeruginosa is one of the most important bacterial pathogens in immunocompromised patients, and the lipopolysaccharide (LPS) of this organism is a key factor in virulence and both innate and acquired host responses to infection. In this study, we prepared a nanoconjugate vaccine composed of P. aeruginosa detoxified lipopolysaccharide (D-LPS) and gold nanoparticles (Au NPs) and evaluated its potential as a vaccine candidate against P. aeruginosa infections. Materials and Methods: LPS from P. aeruginosa strain PAO1 was extracted by the hot phenol method with some modifications and then detoxified. Au NPs were synthesized by the reduction of hydrochloroauric acid trihydrate by sodium borohydride and then coupled to D-LPS via electrostatic interaction. Mice were subcutaneously injected in the tail base with 20 µg of D-LPS, D-LPS-Au NPs, Au NPs, and PBS. IgG titers were evaluated by ELISA and whole-cell ELISA methods. The immunized and control group mice were challenged with a 2×LD50 (7.5×107 CFU) of P. aeruginosa strain PAO1. Results: Mice vaccinated with D-LPS and D-LPS-Au NPs elicited a significant amount of IgG antibodies. Nanoconjugated LPS generated a significantly higher antibody titer compared with D-LPS alone. Also, immunization of mice with D-LPS-Au NPs increased survival times against challenge with 7.5×107 CFU (2×LD50) of P. aeruginosa strain PAO1. Conclusion: Our results showed that the suggested vaccine composed of P. aeruginosa D-LPS and Au NPs had a significant potential to protect against P. aeruginosa infections.
Gold Nanoparticles
Immune response
Lipopolysaccharide
Nanovaccine
Pseudomonas aeruginosa
2021
02
01
203
212
https://ijbms.mums.ac.ir/article_17189_c16cc94f47bd5aa49947fd52adfb5f30.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
2
Respiratory syncytial virus infection of microglia exacerbates SH-SY5Y neuronal cell injury by inducing the secretion of inflammatory cytokines: A Transwell in vitro study
Xiao-Yan
Zhang
Xiao-Cheng
Zhang
Hai-Yang
Yu
Yun
Wang
Jason
Chen
Yang
Wang
Li
Yu
Guo-Xin
Zhu
Xiu-Jing
Cao
Sheng-Hai
Huang
Objective(s): To elucidate the mechanism of Respiratory Syncytial Virus (RSV) infection and central neuronal disease and to understand the role of microglia in neuronal injuries during RSV infection.Materials and Methods: The effects of RSV and the cytokines produced by RSV-infected CHME-5 microglial cells on SY5Y neuronal cells were evaluated based on an in vitro Transwell coculture system. Five treatment groups were established in this study, including the normal control SY5Y group, RSV+SY5Y infection group, (cytokine+CHME-5)+SY5Y Transwell group, (RSV+CHME-5)+SY5Y Transwell group, and (RSV+cytokine+CHME-5)+SY5Y Transwell group. The morphological and physical alterations in SY5Y cells and their synapses were analyzed by confocal microscopy. The mRNA and protein expression levels of TLR3/RIG-I, as well as the expression of Hv1, in microglia were measured by qRT-PCR and Western blot assays. In addition, the apoptosis ratio of neuronal cells was determined by flow cytometry.Results: RSV infection activated the protein expression of Hv1 protein in microglia in vitro (p <0.05), induced morphological changes in SY5Y cells, lengthened synapses (73.36±0.12 μm vs 38.10±0.11 μm), simultaneously activated TLR3 and RIG-I protein expression (p <0.05), upregulated the secretion of the inflammatory cytokines TNF-α, IL-6, and IL-8 (p <0.01), and increased the apoptosis rate of SY5Y cells (p <0.01).Conclusion: The results demonstrate that RSV infection of microglia can induce SY5Y neuronal cell injury and stimulate apoptosis through inflammatory cytokine release.
Cytokines
In Vitro Techniques
Microglia
Neurons
Respiratory syncytial virus infections
2021
02
01
213
221
https://ijbms.mums.ac.ir/article_17188_e834cc7a5e3dfab5c51c634ac8fb5b0b.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
2
Sphingomyelin liposome bearing whole Leishmania lysate antigens induce strong Th2 immune response in BALB/c mice
Nazanin
Biari
Seyedeh Hoda
Alavizadeh
Omid
Chavoshian
Azam
Abbasi
Zahra
Saberi
Seyed Amir
Jalali
Ali
Khamesipoure
Mahmoud Reza
Jaafari
Ali
Badiee
Objective(s): Whole Leishmania lysate antigens (WLL) has been shown to be effective to tackle leishmaniasis in murine models. Although liposomes can be considered as promising vaccines, the activity of phospholipase-A (PLA) in WLL, breeds difficulties to preparing stable liposomal WLL. One strategy to overcome this shortcoming is to use lipids such as sphingomyelin (SM) which is resistant against PLA. This study aim is formulating stable SM liposomes containing WLL and comparing their adjuvant effects with another first generation vaccine , i.e. solube Leishmania Antigen (SLA) liposomes in BALB/c mice. Materials and Methods: BALB/c mice were immunized subcutaneously, three times with 2-week intervals, with Empty-liposome (E-lipo), Particulate WLL, Liposome-WLL, Liposome-SLA and control Buffer, three times every 2-week. Protection was assessed through measuring the swollen footpads and the load of parasites in the spleen. Other factors were used to assess the response of immune system by means of IgG subclasses, IL-4 and IFN-γ levels and intracellular cytokine assay in cultured splenocytes. Results: Although liposomal WLL were stable in terms of physicochemical properties, mice received Liposome-WLL did not reduce footpad swelling. The load of parasites in spleen and levels of IL-4- were also higher compared to other immunized groups. In terms of IgG isotypes, no considerable difference observed in mice received Liposome-WLL or other formulations. Conclusion: Liposome-WLL could be a suitable vaccine delivery system when a Th2 response is desired. Also, further studies are warranted to fully understand the role of sphingomyelin in inducing an immune response.
BALB C mouse Humoral immunity Leishmaniasis vaccines Liposomes Phospholipase
a
2021
02
01
222
231
https://ijbms.mums.ac.ir/article_17192_4305b47f7d9de57c09790d338a5c218d.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
2
Lettuce-avicularin treatment reverses insulin resistance through stimulation of glycolytic kinases and insulin signaling molecules
Joy
Amadi
Peter
Amadi
Uche
Njoku
Chioma
Onitchi
Objective(s): In order to recommend a more effective approach to manage insulin resistance, we monitored the activities of glycolytic kinases, insulin signaling molecules, and incretin hormones and identified the possible targets related to the insulin-sensitizing effects of combined pharmacological and dietary intervention involving avicularin and lettuce.Materials and Methods: Insulin resistance was induced in rats with a fructose-rich diet and confirmed from baseline analysis of FBS (>250 mg/dl), insulin (>25 µIU/ml), and HOMA-IR (>10). For 12 weeks, the insulin-resistant rats were treated exclusively with 5000 mg/kg b.w avicularin (DAvi) or by dietary placement on lettuce (DLet) or a combination of both and compared with non-insulin resistant rats.Results: Avicularin reversed alterations in HbA1c and insulin levels. DLet produced no significant effect on the incretins GLP 1 (P=0.909) and GIP (P=0.990), but DAvi slightly stimulated GLP 1 but not GIP. A strong positive correlation was found between improved β-cell responsiveness and the insulin signaling molecules: Akt2 (r=0.7248), IRS 1 (r=0.5173), and PI3K (r=0.7892). Only the combined avicularin and lettuce reversed the Akt2 levels (P=0.728). The lettuce meal slightly stimulated PI3K but normalized IRS 1 while avicularin treatment slightly stimulated IRS 1 but restored the PI3K levels (P=0.815). The positive correlation between β-cell responsiveness and hexokinase (r=0.5959), PFK (r=0.6222), and PK (r=0.6591) activities were statistically significant. Alterations in glycolytic kinases were reversed by DLet and in combination with avicularin.Conclusion: A combined pharmacological and dietary approach with avicularin and lettuce is required to effectively reverse insulin resistance.
Avicularin
Glycolysis
Incretins
insulin resistance
Insulin signaling
Lettuce
2021
02
01
232
239
https://ijbms.mums.ac.ir/article_17132_6690725d3e405ce9c86167309be68e95.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
2
Gallic acid treats dust-induced NAFLD in rats by improving the liver’s anti-oxidant capacity and inhibiting ROS/NFκβ/TNFα inflammatory pathway
Hafseh
Fanaei
Seyyed Ali
Mard
Alireza
Sarkaki
Gholamreza
Godarzi
Layasadat
Khorsandi
Objective(s): The burden of disease and death related to environmental pollution is becoming a major public health challenge, especially in developing countries. This study was designed to investigate the effect of dust exposure on liver function and its structure in rats. Gallic acid (GA) as a potent anti-oxidant was also used to treat NAFLD in rats exposed to dust. Materials and Methods: Twenty-four rats were randomly assigned into 3 groups: CA, Dust+N/S (after stopping dust exposure, rats received normal saline as vehicle, 1 ml, orally for 14 consecutive days), and Dust+GA (after stopping dust exposure, rats received GA at 100 mg/kg, orally for 14 consecutive days). Rats were exposed to CA/ dust for 6 weeks on alternate days. At the end of experiments, rats were anesthetized, their blood samples and liver sections were taken to perform molecular, biomedical and histopathological evaluations.Results: Dust exposure induced NAFLD features in rats. It increased the serum levels of liver enzymes, LDL, TG, cholesterol, MDA, and mRNA expression of NFκβ, TNFα, IL-6, HO1, and miRs [122 and 34a], while decreasing serum levels of HDL and liver TAC. Treatment with GA improved liver enzymes, serum levels of miRs, TG, expression of NFκβ, TNFα, IL-6, Nrf2, and HO1 and liver MDA and TAC levels, while it could not improve HDL, LDL, and cholesterol.Conclusion: This study showed dust exposure induced NAFLD in Wistar rats through inducing oxidative stress. Oxidative stress through activating the inflammatory pathways caused NAFLD features. Gallic acid treatment by inhibiting oxidative stress effectively protected liver function against dust induced inflammation.
Dust Gallic acid NAFLD Nrf2 Rat TNF
α
2021
02
01
240
247
https://ijbms.mums.ac.ir/article_17354_a4276dea051f5e12548238b04b084742.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
2
Prevention of cisplatin-induced nausea and vomiting by seabuckthorn (Hippophae rhamnoides L.) seed oil: Insights at the level of orexin-A in rats
Wen
Yuan
Hongbo
Wang
Yanling
Gong
Objective(s): Nausea and vomiting are perennial problems in cancer patients undergoing chemotherapy. Orexin-A (OXA) has been shown to regulate feeding and gastric motility. Seabuckthorn (Hippophae rhamnoides L.) seed oil (SSO) has been proved to promote digestion and bowel movements. We investigated whether SSO alleviated cisplatin-induced vomiting and its possible mechanism involved in OXA. Materials and Methods: Rats were randomly divided into normal control group (NCG), cisplatin group (CG), SSO low-dose group (SLG), SSO middle-dose group (SMG) SSO high-dose group (SHG), and ondansetron group (OG). Rats were pretreated respectively with SSO (0.850, 1.675, and 3.350 g/kg·BW) and ondansetron (2 mg/kg·BW) in SLG, SMG, SHG, and OG for 6 days, and the same volume of saline in NCG and CG groups. On the 6th day, cisplatin (6 mg/kg, IP) was administered in all groups except NCG. The cumulative food and kaolin intake, gastric emptying, plasma OXA level, OX1R mRNA and protein expression in the hypothalamus and brainstem, and OXA expression in the lateral hypothalamic area (LHA) were observed, and the HPLC method was used to analyze the composition of SSO. Results: Kaolin intake in cisplatin-induced vomiting rats was significantly reduced (p <0.05) and gastric emptying delayed by cisplatin was improved (p <0.05-0.01) by pretreatment with SSO. Plasma OXA concentration, OX1R expression in the hypothalamus and brainstem increased significantly (p <0.05–0.01). Furthermore, OXA expression in LHA also increased significantly (p <0.05). Conclusion: SSO prevents cisplatin-induced vomiting in rats, which is possibly involved in increasing peripheral and central OXA and the expression of OX1R in the hypothalamus and brainstem.
Cisplatin
induced vomiting LHA Orexin 1 receptor Orexin
A Seabuckthorn (Hippophae
rhamnoides L.) seed oil
2021
02
01
248
255
https://ijbms.mums.ac.ir/article_17133_ad82a9608bdd0fccdb94d6b3925e7ead.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
2
Vitamin B12 and estradiol benzoate improve memory retrieval through activation of the hippocampal AKT, BDNF, and CREB proteins in a rat model of multiple sclerosis
Narjes
Taherian
Gholamhassan
Vaezi
Ali
Neamati
Leila
Etemad
Vida
Hsojjati
Mahmoud
Gorji-Valokola
Objective(s): Multiple sclerosis (MS) causes extensive damage in the hippocampus. Vitamin B12 (vit B12) and estradiol benzoate (EB) have anti-inflammatory and re-myelination properties that make them proper in improvement of cognitive impairment. This study aimed to evaluate the effects of these compounds on learning and memory disturbances.Materials and Methods:77 adult male rats were implanted with stainless steel guide cannula bilaterally into the hippocampal area. The animals received 3 μl intrahippocampal EtB 0.01% and were randomly divided into eleven groups (7 rats/group). The groups included control, peanut oil (sham1), distilled water (sham 2), vit B12 (0.25, 0.5, 1 mg/kg), EB (25 and 50 mg/kg), vit B12 (0.25 mg/kg) plus EB (25 mg/kg), vit B12 (0.5 mg/kg) plus EB (25 mg/kg), and vit B12 (1 mg/kg) plus EB (50 mg/kg). The control group received intrahippocampal saline (as solvent). The locomotor activity and learning and memory functions were evaluated by open-field and shuttle-box tests, respectively. AKT, CREB, and BDNF levels were analyzed by Western blotting. Results: This study has found significant deficit in passive avoidance learning, locomotor activity, as well as decrease in the levels of phosphorylated AKT, BDNF, and CREB in groups that received EtB. Vit B12 (1 mg/kg), EB (50 mg/kg), and their combination markedly improved these side effects. Conclusion: This study demonstrated that vit B12 and estradiol benzoate, especially in combination therapy, can be helpful in treatment of memory problems and MS-induced dysfunction through activation of the hippocampal AKT, BDNF, and CREB proteins.
Estradiol benzoate
Hippocampus
Memory
Multiple Sclerosis
Vitamin B12
2021
02
01
256
263
https://ijbms.mums.ac.ir/article_17353_4bf9ae4656ca78a76fd4ffacf06186eb.pdf