The significance of protein coronas on the biological fates of nanoparticles has been widely recognized. Therefore, the alterations on biological effects caused by protein coronas need systemic study ...and interpretation to design novel safe and efficient nanomedicines. In the present study, we present a comprehensive quantitative analysis of the protein coronas on gold nanorods modified with various surface ligands of different chemical compositions and charges. The design of surface ligands is of utmost importance for the functionalization of nanoparticles, and further, the ligand-induced biological identity determines the fate of nanoparticles in the human body. We found that the surface chemistry influences the composition of the protein corona more profoundly than surface charge. Since the first and most important challenge for administrated nanomedicines is navigating the interaction with macrophages, we further investigated how the surface chemistry-induced specific protein corona affects the phagocytosis and immune responses of macrophages exposed to the corona–nanoparticle complexes. Our results reveal that the protein corona alters the internalization pathways of gold nanorods by macrophages via the interactions of the predominant coronal proteins with specific receptors on the cell membrane. The cytokine secretion profile of macrophages is also highly dependent on the adsorption pattern of the protein corona. The more abundant proteins involved in immune responses, such as acute phase, complement, and tissue leakage proteins, present in the acquired nanoparticle corona, the more macrophage interleukin-1β (IL-1β) released is stimulated. The ligand–protein corona composition-immune response coefficient analysis may serve next-generation nanomedicines with high efficiency and good safety for better clinical translation.
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IJS, KILJ, NUK, PNG, UL, UM
Metal ions are essential components that help maintain the processes of normal life, and they can be used to fabricate self-assembled building blocks for peptide derivatives, proteins and nucleic ...acids. Here, we have developed a novel strategy to construct supramolecular hydrogels modulated using metal cations. Upon introducing a variety of metal ions into aqueous solutions of a gelator (naproxen-FF), including a nonsteroidal anti-inflammatory drug (NSAID) and dipeptide, we obtain stable hydrogels under neutral or alkaline conditions. It is found that these hydrogels with three-dimensional nanofiber networks exhibit excellent mechanical properties and thixotropy, as well as superb responsivity to multiple metal ions. Due to the significance of potassium ions in biological processes, the K-triggered hydrogel has been chosen as a model, and its self-assembly mechanism has been explored
via
various spectral analysis processes. In addition, the self-assembly performances of peptides are significantly affected by the chemical structures of the gelator molecules. This work provides deep insight into the aggregation mechanism of dipeptide-conjugating drug molecules through introducing a variety of metal ions, laying the foundation for further biological applications.
Naproxen-FF shows superb responsiveness to multiple metal ions and its assembly capacity is obviously improved due to its methoxy group.
Aging and menopause effect on body composition and energy balance. Estrogen (E2) plays an important role in body’s metabolism. The aim of the present study was to determine changes in leptin function ...in young intact and ovariectomized (OVX) animals in comparison to the aged animals treated with E2. Young (Intact and OVX 4 months) and aged (19–21 months) female mice were fed High-fat diet (HFD) for 12 weeks and, then they were divided into eight groups including: Intact + OIL, Intact + E2, Intact + Pair body weight (PBW), OVX + OIL, OVX + E2, OVX + PBW, Aged + OIL, and Aged + E2. E2 was administered subcutaneously every four days for four weeks. Responsiveness to leptin was assessed by measuring energy balance components. Results showed that eating HFD increased weight and calorie consumption in young mice, and chronic treatment with E2 decreased both these variables in young animals. E2 only improved the sensitivity to leptin in young animals. Treatment with E2 resulted in increased α-MSH neuropeptide, reduced NPY and AgRP neuropeptides in the brain, and decreased serum leptin in the young animals. Also, treatment with E2 increased the expression of p-STAT3 molecular level in the hypothalamic arcuate nucleus (ARC) in the young animals. Our results indicated that response to E2 depended on age and E2 protects young HFD fed mice from obesity and improves leptin sensitivity.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Consumption of a high-fat diet (HFD) is associated with an increased incidence of inflammatory diseases and metabolic disorders. Also, these disorders will increase in women with aging and menopause, ...which is probably due to the reduced role of estradiol (E2). Selective estrogen modulators including tamoxifen (TAM), which acts through estrogen receptors, have important metabolic effects. This study aimed to determine whether TAM and E2 have protective effects on inflammation caused by HFD in young and aged mice. Methods: Four-month-old (Sham and ovariectomized OVX) and 20-month-old female C57BL/6J mice were used in this study. After feeding them with HFD for 12 weeks, they were divided into nine groups consisting of Sham + Oil, Sham +TAM, Sham + E2, OVX + Oil, OVX +TAM, OVX + E2, Aged + Oil, Aged +TAM, and Aged + E2. TAM and E2 were injected subcutaneously every four days for four weeks. At the end of the experiments, the mice’s blood was sampled. The serum cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) were also determined using ELISA kits. Results: The results revealed that HFD increased inflammation by reducing IL-10 and increasing TNF-a/IL-10 and IL-6/IL-10 ratio in young and aged mice, and TAM and E2 therapy resulted in a significant decrease in TNF-α and IL-6, and an increase in IL-10 in young and aged mice. Conclusion: In conclusion, the results of this study indicated that TAM, in addition to being used as an anticancer drug, can reduce HFD-induced inflammation in both young and aged mice. Therefore, probably it is a good candidate to substitute E2.
The cancer registry system is an important part of the cancer control program. Improper coding of cancers leads to misclassification and incorrect statistical information about cancer. Therefore, in ...this study, the main objective of the qualitative analysis was the accuracy in assigning the codes to the pathological reports in the centers responsible for cancer registry. This study was descriptive, retrospective and applied. The data source in this study included 15,659 pathology reports received during the years 2017-2019 in the population-based cancer registry centers of Mazandaran province. Out of 1800 reports, 1765 samples of reports were selected and analysis was done on them by stratified random sampling method. A researcher-made checklist was used to collect data, and the Kappa agreement coefficient and Cohen's agreement percentage were presented to check the accuracy of the reports. STATA13 was used for data analysis. 1150 of 1765 pathology reports (65.0%), did not have a topographic, morphological and behavioral codes and 410 (23.2%) had grade codes. The Kappa coefficient in reports with a topography code was 0.916 and with a morphology code it was 0.929, respectively. In behavior coding, the highest agreement is in the category of benign cancers at 65.2% and in grade coding in the category without grade is 100%. The most reports were on carcinoma morphology, and the Kappa coefficient in morphology codes has almost complete reliability. In terms of behavior coding, there was the most agreement in the category of benign cancers. The Kappa coefficient in given behavior codes has low reliability.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Type 2 diabetes causes structural and functional changes in the myocardium, which is called cardiomyopathy. Diabetic cardiomyopathy (DCM) is a distinct primary disorder process, independent of ...coronary artery disease, which leads to heart failure in diabetic patients. Also, DCM is a multifaceted disorder that is one of the leading causes of death in elderly and postmenopausal women. Menopause is associated with decreased and stopped ovarian function, which reduces and stops the production of ovarian hormones, especially estrogen. Moreover, menopause is associated with an increased risk of cardiovascular diseases. Sex steroids such as 17-β estradiol have a variety of protective effects on many tissues in the body, including the cardiovascular system. In this article, the concept of DCM, the underlying molecular signaling pathway, and, finally, the role of 17-β estradiol as one of the most important estrogens in moderating DCM are discussed to provide a theoretical basis for in-depth study.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Carbonic anhydrase (CA) IX overexpresses exclusively on cell membranes of hypoxic tumors, regulating the acidic tumor microenvironment. Small molecules of CA inhibitor modified with short peptide ...successfully achieve CA IX-targeted self-assembly that localizes CA inhibitors on hypoxic cancer cell surfaces and enhances their inhibition efficacy and selectivity. CA IX-related endocytosis also promotes selective intracellular uptake of these nanofibers under hypoxia, in which nanofiber structures increase in size with decreasing pH. This effect subsequently causes intracellular acid vesicle damage and blocks protective autophagy. The versatility of tunable nanostructures responding to cell milieu impressively provokes selective toxicities and provides strategic therapy for hypoxic tumors. Moreover, in vivo tests demonstrate considerable antimetastatic and antiangiogenesis effects in breast tumors, and particularly remarkable enhancement of antitumor efficacy in doxorubicin administration. With its biocompatible components and distinctive hypoxia therapies, this nanomaterial advances current chemotherapy, providing a new direction for hypoxic cancer therapy.
Tumor blood vessels have been reported to be abnormal in both structure and function compared with those in normal tissues, leading to a hostile microenvironment and inadequate antitumor drug ...delivery. Dopamine, a chemical messenger, is proven to inhibit angiogenesis and improve tumor vessel normalization. Here, a mesoporous silicon nanoparticle (MSN) is constructed that is responsive to the weakly acidic pH of the tumor extracellular matrix for steady delivery and tumor‐localized release of dopamine. Then MSNs are functionalized with amine conjugated phenylboronicacid molecules, and dopamine is loaded by reacting with phenylboronic acid. In a weakly acidic environment, MSNs intelligently release dopamine due to the hydrolysis of boronic‐ester bond between dopamine and phenylboronic acid, resulting in an evident inhibition of vascular endothelial cell migration and tubule formation. It is shown that loading of dopamine into the functional MSNs significantly prolong the circulatory half‐life of this small molecule. After intravenous injection to tumor bearing mice, this nanoformulation induce tumor blood vessel normalization, thereby improving the antitumor chemotherapeutic efficacy of doxorubicin. This study demonstrates that the pH‐responsive MSN offers great potential for delivery of dopamine in vivo and the normalization of tumor vessels by dopamine can provide an auxiliary treatment for cancer chemotherapeutic drugs.
Normalization of tumor blood vessels can facilitate the drug delivery. Mesoporous silicon nanoparticles are modified and functionalized to deliver dopamine (DA) as a normalized factor with pH‐sensitive bond to protect it from oxidation. DA can normalize vessels formation by its effect on vascular endothelial growth factor. Normalization of vessels improves the antitumor chemotherapeutic efficiency of doxorubicin.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Asafoetida is a gum derived from Ferula assa-foetida, which is used in traditional Iranian medicine to treat some reproductive system disorders. The effects of asafoetida on ovarian tissue, ...expression of certain genes associated with polycystic ovary syndrome (PCOS), and levels of liver, kidney, and blood cell factors after treatment in a rat model were investigated.
Thirty rats were divided into five groups: normal, polycystic, and treatment with three doses of asafoetida (12.5, 25, and 50 mg/kg for 3 weeks after PCOS induction). PCOS was induced by letrozole at a dose of 1 mg/kg administered orally for 3 weeks. Blood samples were taken, and the ovaries were removed and prepared for histomorphometric examination. Liver and kidney parameters were measured. The mRNA expression levels of luteinizing hormone receptor, CYP11A1, adenosine monophosphate-activated protein kinase, adiponectin, and adiponectin receptors 1 and 2 were also measured by real-time polymerase chain reaction.
The levels of liver, kidney, and blood parameters did not significantly differ between the treatment groups and the control group. At doses of 25 and 50 mg/kg, ovarian histopathology, especially the thicknesses of the theca and granulosa layers, was significantly improved relative to the PCOS group. The expression of target genes also improved in the 25 and 50 mg/kg treatment groups.
Asafoetida can be used to treat PCOS as a complementary approach to conventional therapies. Asafoetida appears to act by regulating and activating metabolic and ovarian cycle enzymes.
Background and Aim: Deep vein thrombosis, especially in the lower extremities, is one of the complications of immobility. Major surgeries, especially orthopedic surgeries and inpatient care in the ...intensive care unit, predispose the patients to such complications. The aim of this study was to compare the prevalence rats of venous thromboembolism between the patients treated with enoxaparin and subcutaneous heparin in the intensive care unit. Materials and Methods: This was a retrospective cross-sectional study. Sampling method was census. All the patients who had been admitted to the intensive care units of Imam Khomeini Hospital in Ahvaz from the beginning of September 2017 to the end of December 2017, were entered into this study. Data were extracted from the patients' medical records and recorded in a checklist for every patient. Using SPSS20 software, data were analyzed by descriptive and analytical statistics. Results: Out of 600 patients, 64 (10.66%) patients had venous thromboembolism, of which 35 patients (54.7%) were in the heparin group and 29 patients (45.3%) in the enoxaparin group (P >0.05). 18 patients had deep venous thrombosis (3%), among them 13 (72.22%) patients were in the heparin group and 5 (27.78%) patients in the enoxaparin group (P <0.05). Conclusion: In this study, enoxaparin administration was more effective than heparin in the prevention of deep vein thrombosis but the effects of these two drugs were the same in the prevention of pulmonary thromboembolism. More concrete conclusions require further studies with control of underlying and confounding factors.
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