The Role of Quercetin for the Treatment of Endometriosis and Endometrial Cancer: A Comprehensive Review.

Endometrial glands and stroma can be seen outside the uterine cavity in endometriosis, a gynecological disorder linked to estrogen dependency. Hormonal therapies, surgical excision, and non-steroidal anti-inflammatory drug therapy are among the traditional endometriosis treatments, however, various side effects limit their efficacy. Therefore, it is vital to research complementary and alternative therapeutic modalities to decrease the side effects of conventional therapies. While the search for the best endometriosis treatment continues, the focus is being paid to the assistance provided by polyphenols, notably quercetin. A broad spectrum of health-improving benefits of quercetin includes interactions with endometriosis-related molecular targets such as cell proliferation, apoptosis, invasiveness, inflammation, and oxidative stress. According to already-known research, medicines that mimic the physiological effects of quercetin are good candidates for creating novel endometriosis therapies. This review aims to comprehensively review quercetin's potential as a non-pharmacological treatment for endometriosis by interacting with several cellular and molecular targets.

Entrapment of Digoxin-KLH Conjugate in Alginate/Chitosan Nanoparticles: A New Antigen Delivery System For Production of Anti-digoxin Antibodies.

BACKGROUND: Nanoparticles have received more and more attention in the vaccine and drug delivery systems field due to their specific properties. In particular, alginate and chitosan have been known as the most promising nano-carries. Digoxin-specific antibodies effectively manage acute and chronic digitalis poisoning using sheep antiserum. OBJECTIVE: The present study aimed to develop alginate/chitosan nanoparticles as a carrier of Digoxin-KLH to promote the immune response by improving the hyper-immunization of animals. METHOD: The nanoparticles were produced by the ionic gelation method in mild conditions and the aqueous environment, which leads to the production of particles with favorable size, shape, high entrapment efficiency, and controlled release characteristics. RESULT: The synthesized nanoparticles of 52 nm in diameter, 0.19 in PDI, and -33mv in zeta potential were considerably unparalleled and characterized by SEM, FTIR, and DSC. Nanoparticles resembled a spherical shell, smooth morphology, and homogeneous structure shown by SEM images. FTIR and DSC analyses confirmed conformational changes. Entrapment efficiency and loading capacity were 96% and 50%, respectively, via direct and indirect methods. The invitro conjugate release profile, release kinetics, and mechanism of conjugate release from the nanoparticles were studied under simulated physiological conditions for various incubation periods. An initial burst effect revealed the release profile, followed by a continuous and controlled release phase. The compound release mechanism from the polymer was due to Fickian diffusion. CONCLUSION: Our results indicated the prepared nanoparticles could be appropriate for the convenient delivery of the desired conjugate.

Modulation of microRNAs expression and cellular signaling pathways through curcumin as a potential therapeutical approach against ovarian cancer: A review.

Short non-coding RNAs called microRNAs (miRNAs) control gene expression by either inhibiting translation or degrading messenger RNA. MiRNAs are crucial for many biological functions, and the deregulation of their expression is strongly linked to the emergence of cancer. A single miRNA controls several gene expressions, allowing it to simultaneously control a number of cellular signaling pathways. As a result, miRNAs may be used as therapeutic targets as well as biomarkers for the prognosis and diagnosis of different cancers. Recent research has shown that natural compounds like curcumin, resveratrol and quercetin exert their pro-apoptotic and/or anti-proliferative impacts by modulating one and/or more miRNAs, which inhibits the growth of cancer cells, induces apoptosis, or increases the effectiveness of conventional cancer therapies. Here, we summarize the most recent developments in curcumin's control over the expression of miRNAs and emphasize the significance of these herbal remedies as a viable strategy in the treatment and prevention of cancer.

The Role of High-Fructose Diet in Liver Function of Rodent Models: A Systematic Review of Molecular Analysis.

The present systematic review of animal studies on long-term fructose intake in rodents revealed a significant decrease in the activities of antioxidant enzymes due to a fructose-rich diet. The reduced activity of these enzymes led to an increase in oxidative stress, which can cause liver damage in rodents. Of eight studies analyzed, 5 (62.5%) and 1 (12.5%) used male and female rats, respectively, while 2 studies (25%) used female mice. Moreover, half of the studies used HFCS, but the other half employed fructose in the diet. Hence, it is essential to monitor dietary habits to ensure public health and nutrition research outcomes.

Synthetic selenium nanoparticles as co-adjuvant improved immune responses against methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the leading causes of hospital-acquired infections worldwide, which is resistant to many antibiotics, resulting in significant mortality in societies. Vaccination is a well-known approach to preventing disease. Autolysin, a surface-associated protein in S. aureus with multiple functions, is a suitable candidate for vaccine development. As a co-adjuvant, selenium nanoparticles (SeNPs) can increase the immune system, presumably resulting in increased vaccine efficacy. The present study evaluated the immunogenicity and defense of recombinant autolysin formulated in SeNPs and Alum adjuvants against MRSA. r-Autolysin was expressed and purified by the Ni-NTA affinity chromatography. SeNPs were synthetically obtained from sodium dioxide, followed by an assessment of shape and size using SEM and DLS. Balb/c mice were injected subcutaneously with 20 mg of r-autolysin formulated in Alum and SeNps adjuvants three times with the proper control group in 2 weeks intervals. Cytokine profile and isotyping ELISA were conducted to determine the type of induced immunity. Opsonophagocytosis tests assessed the functional activity of the vaccine, and the bacterial burden from the infected tissues was determined. Results showed that mice receiving SeNps and r-Autolysin had higher levels of total IgG and isotypes (IgG1 and IgG2a) and increased cytokine levels (IFN-γ, TNF-α, IL-12, and IL-4) as compared with those only receiving autolysin and PBS as a control. More importantly, mice immunized with SeNps and r-Autolysin exhibited a decrease in mortality and bacterial burden compared to the control group. We concluded that SeNps could stimulate immune responses and can be used as an adjuvant element in vaccine formulation.

Erratum to "Nanotechnology in Wound Healing; Semisolid Dosage Forms Containing Curcumin-Ampicillin Solid Lipid Nanoparticles, in Vitro, Ex Vivo and in Vivo Characteristics".

[This corrects the article DOI: 10.15171/apb.2018.046.].

Increased urinary arsenic concentration in newly diagnosed type 2 diabetes mellitus: a gender-independent, smoking-dependent exposure biomarker in older adults in Tehran.

Arsenic is ranked in the top ten environmental toxicants but its impact on type 2 diabetes mellitus (T2DM) and its association with other human health effects is contradictory. We aimed in this study to compare the urinary arsenic concentration (u As) in older age adults (> 40 years) and their T2DM subgroup in an age and gender-matched case control study to find the association of u As with, diet, oxidative stress, smoking, anthropometric factors, and lifestyle in our study participants. Face-to-face interviews based on structured questionnaires were conducted on 200 female and male volunteers (100 cases and 100 control). Considering the exclusion criteria, u As concentration and serum biomarkers of oxidative stress (malondialdehyde, superoxide dismutase, catalase) of 30 newly diagnosed T2DM and 30 control were determined by ICP-mass analysis and ELISA reader respectively. Despite the similarities in sociodemographic, diet, and lifestyle factors in males and females and their T2DM subgroups, a 4 times difference in u As levels between T2DM (93.7 ng/L (32)) and their healthy counterparts (23.7 ng/L (2.3)) without meaningful associations with gender, age, BMI, diet, and lifestyle was observed. Mean u As concentration in total population of smokers was significantly higher than non-smokers ((119 ng/L vs. 22.5 ng/L (p = 0.03)) and oxidative stress markers were not significantly higher in T2DM smokers than non-smokers. Chronic arsenic exposure through smoking could be contributed to the incidence of T2DM in older age adults. Oxidative stress markers were not significantly increased in smoker subgroup compared with non-smokers but except smoking pattern, other variables did not affect u As concentration. Precautionary measure to reduce the exposure of people with this element is recommended to prevent the arsenic-induced T2DM in human populations.

Toxicity assessment of superparamagnetic iron oxide nanoparticles in different tissues.

Superparamagnetic iron oxide nanoparticles (SPIONs) have been employed in several biomedical applications where they facilitate both diagnostic and therapeutic aims. Although the potential benefits of SPIONs with different surface chemistry and conjugated targeting ligands/proteins are considerable, complicated interactions between these nanoparticles (NPs) and cells leading to toxic impacts could limit their clinical applications. Hence, elevation of our knowledge regarding the SPION-related toxicity is necessary. Here, the present review article will consider current studies and compare the potential toxic effect of SPIONs with or without identical surface chemistries on different cell lines. It centers on cellular and molecular mechanisms underlying toxicity of SPIONs. Likewise, emphasis is being dedicated for toxicity of SPIONs in various cell lines, in vitro and animal models, in vivo.

Preparation of PEG-grafted chitosan/streptokinase nanoparticles to improve biological half-life and reduce immunogenicity of the enzyme.

Streptokinase, as a thrombolytic drug, is widely used in treatment of cardiovascular disorders and deep vein thrombosis. Streptokinase is immunogenic due to its prokaryotic source, having short biological half-life (i.e. 15 to 30 min) that is not enough for an efficient therapy. In this study, nanoparticles (NPs) of chitosan/streptokinase and polyethylene glycol (PEG)-grafted chitosan/streptokinase were prepared by polyelectrolyte complex method. Particle size of chitosan and PEG-grafted chitosan NPs were 154 ± 42 and 211 ± 47 nm, respectively. Results showed that using PEG in preparation of nanoparticles leads to ~24% decrease in encapsulation efficiency. Encapsulation of streptokinase in the NPs also resulted in a slight reduction in enzymatic activity. However, in vivo findings indicated that response of the immune system was delayed for 20 days and blood circulation time of the enzyme increased up to 120 min by using PEG. Biological half-life of the drug also increased up to twice in PEG-grafted chitosan. In conclusion, PEG-grafted chitosan NPs could be an alternative for delivery of streptokinase to reduce its clinical limitations.

Nanotechnology in Wound Healing; Semisolid Dosage Forms Containing Curcumin-Ampicillin Solid Lipid Nanoparticles, in-Vitro, Ex-Vivo and in-Vivo Characteristics.

Purpose: Wound healing is a natural biologic process, but the duration of it may take too long. Trying to shorten this process is one of the challenges for scientists. Many technologies were applied to achieve this goal as well as nanotechnology. In this study semi solid formulations containing curcumin and ampicillin solid lipid nanoparticles (SLNs) were prepared to evaluate as burn wound healing agent. Methods: Curcumin as an anti-inflammatory and anti-bacterial agent and ampicillin as an antibiotic were applied. In-vitro and in-vivo evaluations were carried out. Particle size, loading efficiency, release profile, morphology and anti-bacterial efficacy of desired nanoparticles were evaluated at first. Then the remaining of the antibacterial effect in semi solid preparations was studied. Animal studies for both toxicology using rabbits and skin burn model using rats were designed. Pathology studies after applying of formulations was done too. Results: Desired nanoparticles were spherical in shape and particle size in range of 112-121 nm, with low zeta potential. For increasing stability of particles they were freeze dried using cryoprotectant. Lyophilized particles show no significant size enlargement. Results showed that both ointment and gel preparations have reasonable anti-bacterial effects, both of them cause increasing in the rate of wound healing in comparison with placebos and control groups and none of the formulations showed acute toxicity. Conclusion: It seems that using nanotechnology could shorten wound healing process to reduce treatment costs and increase compliance of patients.

Toxicity Assessment of Asteraceae Centaurea Repens L Extract in Mice.

The species Asteraceae Centaurea repens (Asteraceae), known as Acroptilon repens, and Talkhe in persian is used in folk medicine as an emetic, anti-epileptic, and anti-malaria herb in many parts of the world but its toxic effects have not determined yet. This study aimed to evaluate the acute and subchronic toxicity of this extract to find its possible adverse health effects through clinical, hematological, biochemical, and histopathological endpoints in both gender of mice. Aerial parts of the plant were air-dried and the terpene extract of aerial parts of plant was provided by percolation using methanol, petroleum ether, and diethyl ether. All clinical, biochemical and histopathological changes were assessed in appropriate endpoints and compared with control group. Although no mortality was seen in acute study by administrating doses up to 2000 mg/kg, repeated dose study on 1000 mg/kg doses in 28 days in both genders showed liver necrosis and rise of liver enzymes (p-value < 0.05). Histopathological studies didn't show any other organ toxicity in dosed up to 1000 mg/kg. At the same time this study showed for the first the antihyperlipidemic properties of the aerial extract of Acroptilin in mice model. The pharmacological and histopathological results of the present study proved that the total parts of Acroptilon repens could be studied for supporting the traditional assertion in folk medicine to heal hyperlipidemia, diabetes, and cancer in lower doses although we performed the present study and concluded liver toxicity by subchronic use of Acropitolon repens extract.

Sub-chronic Dermal Toxicity of Silver Nanoparticles in Guinea Pig: Special Emphasis to Heart, Bone and Kidney Toxicities.

Silver nanoparticles (Ag NPs) have been widely used as new potent antimicrobial agents in cosmetic and hygienic products. Present study compares the tissue levels of Ag NPs in different organs of Guiana Pigs quantitatively after dermal application and analysis the morphological changes and pathological abnormalities on the basis of the Ag NPs tissue levels. Before toxicological assessments,the size of colloidal nanosilver was recorded by X-Ray Diffraction and Transmission Electron Microscope tests and the sizes of samples were recorded in sizes less than 100 nm. For toxicological evaluation, male guinea pigs were exposed to three concentrations of Ag NPs (100, 1000 and 10000 ppm) according to acute pretests for further assessments in subchronic model in a period of 13 weeks . A close correlation between dermal exposure and tissue levels of Ag NPs was found (p < 0.05) and tissue uptakes happened in dose dependent manner with the following ranking: ki dney>muscle>bone>skin>liver>heart >spleen. In histopathological studies, severe proximal convoluted tubule degeneration and distal convoluted tubule were seen in the kidneys of the middle and high-dose animals. Separated lines and marrow space narrow were determined as two major signs of bone toxicities which observed in three different dose levels of Ag NPs. Increased dermal dose of Ag NPs caused cardiocyte deformity, congestion and inflammation. The three different Ag NPs concentration gave comparable results for several endpoints measured in heart, bone and kidney, but differed in tissue concentrations and the extent of histopathological changes. It seems that Ag ions could be detected in different organs after dermal exposure ,which has the potential to provide target organ toxicities in a time and dose dependent manner.

Acute and subchronic toxicity assessment of the hydroalcoholic extract of Stachys lavandulifolia in mice.

Stachys lavandulifolia is used as the herbal tea and its wide and potent medical effects have been reported for the extract in animal studies. This study aimed to find the safety profile of the extract to find the appropriate doses for further human studies. The aerial parts of the plant were air-dried and the hydroalcoholic extract was obtained and concentrated by percolation method with 140 mg/ml concentration. To assess the toxicity profile of this extract, 60 female mice (30 cases, 30 controls, 24.8 ± 2.1 g, 4-6 weeks) were administered the extract by oral gavages in acute (24 hrs), subacute (14 days) and subchronic (45 days) models. All clinical, hematological, biochemical and histopathological changes were assessed in appropriate midpoints and endpoints and compared with control group. Doses up to 140 mg/kg were recognized as maximum tolerated dose in subchronic model. Abnormal changes in kidney and liver weight in treatment groups as well as the significant elevation of biochemical parameters in 45 days study has suggested the possible hepatic and renal toxicity potentials of this extract with doses upper than 140 mg/kg. Doses up 70 mg/kg could be considered as no observable adverse effect level (NOAEL) and could be used in further clinical trials on the possible therapeutic effects of this plant.