Porous conductive and biocompatible scaffolds on the basis of polycaprolactone and polythiophene for scaffolding

Porous conductive and biocompatible scaffolds on the basis of polycaprolactone and polythiophene for scaffolding

Raana Sarvari1 · Bakhshali Massoumi2 · Amir Zareh2 · Younes Beygi‑Khosrowshahi3 · Samira Agbolaghi3

Abstract

The fabrication of novel scaffolds was represented on the basis of conductive and biodegradable copolymers. The star-like polycaprolactone (S-PCL) was synthesized from dipentaerythritol as a core by a catalyst of Sn(oct)8 through ring-opening technique. After functionalization of S-PCL by thiophene, thiophene monomer was polymerized from polycaprolactone ends via chemical oxidation polymerization to reach star-like polycaprolactone–polythiophene (S-PCL–PTh). The scaffolds demonstrated a porous configuration (160–۱۹۰ nm) having the great surface area as well as conductivity of 0.011 S cm−۱٫ The cytocompatibility measurements exhibited thatthe nanofibers were not toxic to the MG63 cells

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pH‑responsive nanosystems based on reduced graphene oxide grafted with polycaprolactone‑block‑poly(succinyloxyethylmethacrylate) for doxorubicin release

pH‑responsive nanosystems based on reduced graphene oxide grafted with polycaprolactone‑block‑poly(succinyloxyethylmethacrylate) for doxorubicin release

Bakhshali Massoumi1 · Raana Sarvari2 · Leila Khanizadeh1 · Samira Agbolaghi3 · Younes Beygi‑Khosrowshahi3

 

Abstract
pH-responsive nanocarriers were synthesized via polycaprolactone-b poly(succinyloxyethylmethacrylate) copolymers grafted onto reduced graphene oxide (rGO-g-PCL-b-PSEMA) for anticancer drug delivery applications. For this propose, ε caprolactone monomer was polymerized from –OH groups of rGO with ring-opening polymerization (ROP) to obtain polycaprolactone grafts (rGO-g-PCL). In the next step, 2 hydroxyethylmethacrylate monomer was polymerized from PCL end through atom transfer radical polymerization to afford rGO-g-PCL-b-poly(hydroxyethylmethacrylate) (PHEMA). The pH-responsive rGO-g-PCL-b-PSEMA was obtained by reacting rGO-g-PCL-b-PHEMA with excess succinic anhydride in pyridine under mild conditions. The pH sensitivity of nanosystems was confirmed via dynamic light scattering at pH values of 4 and 7.4. Doxorubicin encapsulation efficacy was calculated to be 92%. The effect of pH on release behaviors of rGOg- PCL-b-PSEMA nanocarriers was investigated. Therelease rates at pH values of 7.4, 5.4 and 4 were about 52.1, 64.2 and 68.63 wt% after 775 min and at 37 °C. The release rate was improved at tumor simulatedenvironment (42 °C and pH ≤ ۵٫۴).The cytotoxic effects of nanosystems were appraised by 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the results indicated that novel smart nanosystems were nontoxic to MCF-7 cells and can be applied as anticancer drug deliver

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The potential therapeutic efect of melatonin on human ovarian cancer by inhibition of invasion and migration of cancer stem cells

The potential therapeutic efect of melatonin on human ovarian cancer by inhibition of invasion and migration of cancer stem cells

Maryam Akbarzadeh1,2, Ali Akbar Movassaghpour3, Hossein Ghanbari4, Maryam Kheirandish5, Nazila Fathi Marouf6, Reza Rahbarghazi7, Mohammad Nouri1,2 &Nasser Samadi2,6

ABSTRACT

There is an urgent need to identify targeting molecules to control invasion and metastasis in cancer patients. We frst isolated cancer stem cells (CSCs) from SKOV3 ovarian cancer cells and then investigated the role of melatonin in invasiveness and migration of CSCs compared to SKOV3 cells. The proportion of CSCs in SKOV3 cells was as low as 1.28% with overexpression of both CD133 and CD44. The ability of spheroid formation along with SOX2 overexpression revealed a high self-renewal potential in isolated cells. Melatonin (3.4mM) inhibited proliferation of CSCs by 23% which was confrmed by a marked decrease in protein expression of Ki67, as a proliferation marker. Applying luzindole, a melatonin receptor 1, 2 inhibitor, partially abolished anti-proliferative efect of melatonin. Melatonin also decreased Epithelial mesenchymal transition (EMT) related gene expressions including ZEB1, ZEB2, snail and vimentin with increase in E-cadherin as a negative EMT regulator. Incubation of CSCs with melatonin showed a marked decrease in matrix metalloproteinase 9 (MMP9) expression and activity. Melatonin also inhibited CSCs migration in a partially receptor dependent and PI3k and MAPK independent manner. Melatonin can be considered as an important adjuvant to control invasion and metastasis especially in patients with high melatonin receptor expression.

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New insights to structure and immunological features of Leishmania lipophosphoglycan3

New insights to structure and immunological features of Leishmania lipophosphoglycan3

  Maryam Hosseinia a, Mostafa Haji-Fatahalihaa a, Abolfazl Miahipour b, Mehdi Yousefic
a Stem Cell and Regenerative Medicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
b Department of Medical Parasitology and Mycology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
c Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

ABSTRACT

Leishmaniasis is a major public infectious disease caused by the genus Leishmania. No effective drug or vaccination
strategy for leishmaniasis has been designed yet. Several intracellular Leishmania antigens have been
recognized to serve in vaccination, ensuring long-lasting protection against Leishmania infection.
Lipophosphoglican 3 (LPG3) as a member of the heat shock protein 90 family involves in the synthesis of
lipophosphoglycan (LPG) and implicates in parasite virulence. Regarding the immunological properties of LPG3
particularly its N-terminal fragment, it would be considered as a favourable adjuvant in Leishmania vaccination.

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Natural killer T cells in Preeclampsia: An updated review

Natural killer T cells in Preeclampsia: An updated review

Vida Hashemi a,b,d, Sanam Dolati a,c,d, Arezoo Hosseini a,c,d, Tohid Gharibi a,c,d, Shahla Danaiie ,Mehdi Yousefi c,d
a Stem Cell and Regenerative Medicine Institute, Tabriz University of Medical Sciences, Tabriz, Ira
b Department of Basic Science, Faculty of Medicine, Maragheh University of Medical Sciences, Maragheh, Iran
c Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
d Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
e Gynecology Department, Eastern Azerbaijan ACECR ART Center, Eastern Azerbaijan Branch of ACECR, Tabriz, Iran

ABSTRACT

Preeclampsia (PE), as a pregnancy-specific syndrome, has become one of the main causes of maternal and fetal mortality worldwide and is known as a major risk factor for preterm birth. PE is typically characterized by hypertension, significant proteinuria, and an excessive maternal systemic inflammatory response. Recent evidences provide support for the notion that Natural killer T (NKT) cells (a small, but significant immunoregulatory T cell subset of human peripheral blood lymphocytes) play pivotal roles in pregnancy. NKT cells with unique transcriptional and cytokine profiles exist in different peripheral tissues acting as mediators between the innate and adaptive immune systems. NKT cells secrete Interleukin-4 (IL-4) and Interferon-γ (IFN-γ) which might regulate the balance between Type 1 T helper (Th1) and Type 2 T helper (Th2) responses. During pregnancy, maternal immunity is biased towards type II cytokine production to inhibit the function of type I cytokines that could be harmful for the developing fetus. This shift to type II cytokines does not occur in preeclamptic patients. In this review, we discuss the numbers, phenotype, changes, and the functional activity of Natural killer T (NKT) cells during normal pregnancy and preeclampsia

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(Effect of Intravenous immunoglobulin on Th1 and Th2 lymphocytes and improvement of pregnancy outcome in recurrent pregnancy loss (RPL

Effect of Intravenous immunoglobulin on Th1 and Th2 lymphocytes and improvement of pregnancy outcome in recurrent pregnancy loss

Majid Ahmadia,b,c,1 , Samaneh Abdolmohammadi-vahida,b,c,1 , Mahnaz Ghaebia,b,c , Leili Aghebati-Malekia,b,c , Amir Afkhamb,c , Shahla Danaiid , Sedigheh Abdollahi-Fardd , Lida Heidarid , Farhad Jadidi-Niaraghb,c , Vahid Younesie , Mohammad Nourif , Mehdi Yousefib,c, *

a Stem Cell and Regenerative Medicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran

bDrug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

c Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

dGynecology Department, Eastern Azerbaijan ACECR ART Center, Eastern Azerbaijan Branch of ACECR, Tabriz, Iran

ePishtaz Teb Zaman Diagnostics, Tehran, Iran

f Department of Biochemistry and Clinical Laboratories, Tabriz University of Medical Sciences, Tabriz, Iran

A B S T R A C T

Background: Women with elevated natural killer (NK) cell frequency and function during pregnancy, suffer from recurrent pregnancy loss (RPL). In the present study, the possible effect of intravenous immunoglobulin (IVIG) administration on Th1 and Th2 cell frequency, cytokine secretion, and expression of transcription factors is compared between RPL patients and control group. Materials and methods: Totally, 44 women with a history of RPL (32 women as treated group and 12 as control group) were enrolled in the study. The frequency of Th1 and Th2 lymphocytes, the expression of transcription factors related to these cells and the serum levels of associated cytokines were assessed by flowcytometry, real-time PCR and ELISA, respectively. All, assessments were performed both before and after treatment with IVIG. Results: A significant reduction in Th1 lymphocyte frequency, transcription factor expression and cytokine levels were observed in IVIG-treated group, while all the above parameters indicated a significant increase for Th2 lymphocytes. Th1/Th2 ratio decreased significantly (p value < 0.0001) at the end of treatment and 28 out of 32 (87.5%) women in IVIG-treated group had live birth in comparison with 5 out of 12 (41.6%) in untreated group. Conclusion: IVIG administration proves to be an efficienttherapeutic strategy which is able to enhance the success rate of pregnancy through a shift in Th2 responses. Furthermore, IVIG presents efficacy for the treatment of reproduction failures especially in subjects with immune cell abnormalities and increased NK cell level and function

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The c-Met receptor: Implication for targeted therapies in colorectal cancer

The c-Met receptor: Implication for targeted therapies in colorectal cancer

Elmira Safaie Qamsari1,2, Sepideh Safaei Ghaderi3,4,

Bahareh Zarei5, Ruhollah Dorostkar6, Salman Bagheri1,2,

Farhad Jadidi-Niaragh1,2,7, Mohammad Hossein Somi8

and Mehdi Yousefi8

Abstract

c-Met (mesenchymal–epithelial transition factor) is a tyrosine kinase receptor activated by hepatocyte growth factor and regulates multiple biological processes, such as cell scattering, survival, and proliferation. Aberrant c-Met signaling has been implicated in a variety of cancer types, including colorectal cancer. c-Met is genetically altered through various mechanisms that is associated with colorectal cancer progression and metastasis. Especially, in colorectal cancer, preclinical evidence for the aberrant activation of the c-Met signaling exists. Accordingly, molecular targeting of c-Met receptor could be a promising strategy, in the treatment of colorectal cancer patients. Recently, it was also shown that crosstalk between c-Met and other cell surface receptors attributes to tumorigenesis and development of therapeutic resistance. Characterization of the molecular mechanisms through which c-Met crosstalks with other receptors in favor of tumor formation and progression remains to explore. This review will describe the mechanisms of aberrant c-Met signaling in colorectal cancer and discuss on additional roles for c-Met receptor through crosstalk with other tyrosine kinase receptors and cell surface proteins in colorectal cancer. Novel therapeutic approaches for c-Met pathway targeting will also be discussed.

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Intravenous immunoglobulin (IVIG) modulates Th17 cells and improves live birth rate in patients with recurrent spontaneous abortion

Intravenous immunoglobulin (IVIG) modulates Th17 cells and improves live birth rate in patients with recurrent spontaneous abortion

Eghbal-Fard SP1P, Ahmadi MP1P, Dolati SP1P, Nouri MP2P, Babaloo
ZP1P, Farzadi LP3P, Jadidi Niaragh FP1P, Yousefi M P1P.
۱٫ Stem Cell and Regenerative Medicine Institute, Tabriz
University of Medical Sciences, Tabriz, Iran.
۲٫ Department of Biochemistry, Tabriz University of Medical
Sciences, Tabriz, Iran.
۳٫ Department of Gynecology, Tabriz University of Medical
Sciences, Tabriz, Iran.
Email: mehdi_yusefi@yahoo.com

Introduction: Recurrent spontaneous abortion (RSA) isa growing problem in the Iran, particularly among women over 30 years of age. In these women, RSAoccurs with both natural and artificial fertilization techniques. There is increasing evidence thatimmunologic factors play an important role in RSA.Th17 cells are recently proposed as new risk factors in RSA. Higher level of IL-17 has been reported in women with unexplained RSA compared with women with normal pregnancies Intravenous Immunoglobulin G (IVIG) was shown to cause immunomodulation in RSA patients.

Materials and Methods: 38 RSA subjects with cellular immune abnormalities were included and peripheral bloods was drawn upon positive pregnancy test. On the same date, IVIG, 400 mg/kg, was administrated intravenously and continue every 4 wk through 28-30 wk of gestation. 12 RSA patients with abnormal cellular immune profile were included as IVIG untreated group. We investigated IVIG effect on Th17 cells frequencies and cytokine secretions and pregnancy outcome in RSA patients before and after treatment.

Results: IVIG treatment significantly reduced the frequency of Th17 cells from 3.94±۱٫۱۲% to 1.83±۰٫۵۶%. Moreover, significant reduction in RORγt and IL-17 mRNAs and cytokine secretions (IL-17 and IL-23) were observed in IVIG treated patients. Pregnancy outcome in IVIG treated subjects (87.5%) was significantly higher than untreated group (41.6%). Conclusion: Our findings shed more light on the mechanisms of IVIG immunomdulatory effects and introduced IVIG as a promising therapeutic approach in RSA patients with cellular immune system abnormalities.

Key words: Recurrent spontaneous abortion, Intravenous immunoglobulin G, Treatment, Th17.