Exploration of the photothermal role of curcumin-loaded targeted carbon nanotubes as a potential therapy for melanoma cancer.

In this research, the hydrophilic structure of multi-walled carbon nanotubes (MWCNTs) was modified by synthesizing polycitric acid (PCA) and attaching folic acid (FA) to create MWCNT-PCA-FA. This modified nanocomplex was utilized as a carrier for the lipophilic compound curcumin (Cur). Characterization techniques including TGA, TEM, and UV-visible spectrophotometry were used to analyze the nanocomplex. The mechanism of cancer cell death induced by MWCNT-PCA-FA was studied extensively using the MTT assay, colony formation analysis, cell cycle assessment via flow cytometry, and apoptosis studies. Furthermore, we assessed the antitumor efficacy of these targeted nanocomplexes following exposure to laser radiation. The results showed that the nanocomposites and free Cur had significant toxicity on melanoma cancer cells (B16F10 cells) while having minimal impact on normal cells (NHDF cells). This selectivity for cancerous cells demonstrates the potential of these compounds as therapeutic agents. Furthermore, MWCNT-PCA-FA/Cur showed superior cytotoxicity compared to free Cur alone. Colony formation studies confirmed these results. The researchers found that MWCNT-FA-PCA/Cur effectively induced programmed cell death. In photothermal analysis, MWCNT-PCA-FA/Cur combined with laser treatment achieved the highest mortality rate. These promising results suggest that this multifunctional therapeutic nanoplatform holds the potential for combination cancer therapies that utilize various established therapeutic methods.

A versatile theranostic magnetic polydopamine iron oxide NIR laser-responsive nanosystem containing doxorubicin for chemo-photothermal therapy of melanoma.

Theranostics nanoparticles (NPs) have recently received much attention in cancer imaging and treatment. This study aimed to develop a multifunctional nanosystem for the targeted delivery of photothermal and chemotherapy agents. Fe3O4 NPs were modified with polydopamine, bovine serum albumin, and loaded with DOX via a thermal-cleavable Azo linker (Fe3O4@PDA@BSA-DOX). The size of Fe3O4@PDA@BSA NPs was approximately 98 nm under the desired conditions. Because of the ability of Fe3O4 and PDA to convert light into heat, the temperature of Fe3O4@PDA@BSA NPs increased to approximately 47 °C within 10 min when exposed to an 808 nm NIR laser with a power density of 1.5 W/cm2. The heat generated by the NIR laser leads to the breaking of AZO linker and drug release. In vivo and in vitro results demonstrated that prepared NPs under laser irradiation successfully eradicated tumor cells without any significant toxicity effect. Moreover, the Fe3O4@PDA@BSA NPs exhibited the potential to function as a contrasting agent. These NPs could accumulate in tumors with the help of an external magnet, resulting in a significant enhancement in the quality of magnetic resonance imaging (MRI). The prepared novel multifunctional NPs seem to be an efficient system for imaging and combination therapy in melanoma.

Stimuli-responsive hydrogel based on natural polymers for breast cancer.

Aims: Breast cancer is the most common malignancy among women in both high- and low-resource settings. Conventional breast cancer therapies were inefficient and had low patient compliance. Stimuli-responsive hydrogels possessing similar physicochemical features as soft tissue facilitate diagnostic and therapeutic approaches for breast cancer subtypes. Scope: Polysaccharides and polypeptides are major natural polymers with unique biocompatibility, biodegradability, and feasible modification approaches utilized frequently for hydrogel fabrication. Alternating the natural polymer-based hydrogel properties in response to external stimuli such as pH, temperature, light, ultrasonic, enzyme, glucose, magnetic, redox, and electric have provided great potential for the evolution of novel drug delivery systems (DDSs) and various advanced technologies in medical applications. Stimuli-responsive hydrogels are triggered by specific cancer tissue features, promote target delivery techniques, and modify release therapeutic agents at localized sites. This narrative review presented innovation in preparing and characterizing the most common stimuli-responsive natural polymer-based hydrogels for diagnostic and therapeutic applications in the breast cancer area. Conclusion: Stimuli-responsive hydrogels display bioinspiration products as DDSs for breast cancer subtypes, protect the shape of breast tissue, provide modified drug release, enhance therapeutic efficacy, and minimize chemotherapy agents' side effects. The potential benefits of smart natural polymer-based hydrogels make them an exciting area of practice for breast cancer diagnosis and treatment.

Metformin enhances anti-cancer properties of resveratrol in MCF-7 breast cancer cells via induction of apoptosis, autophagy and alteration in cell cycle distribution.

Breast cancer is the fifth leading cause of death, worldwide affecting both genders. Accumulating evidence suggests that metformin, an oral hypoglycemic agent used in the management of type 2 diabetes, exerts anti-tumor effects in many cancers, including the breast cancer. Resveratrol, a natural product found abundantly in many fruits, exhibits marked cytotoxic and pro-oxidant effects. This study was designed to investigate the effect of metformin in combination with resveratrol and cisplatin in MCF-7 cells. Study groups were as follows: untreated control group, single treatment groups (metformin, resveratrol, and cisplatin), double treatment groups (metformin + resveratrol, metformin + cisplatin, and cisplatin + resveratrol) and triple treatment groups (metformin + resveratrol + cisplatin). Our results indicated that metformin inhibits proliferation of MCF-7 cells, an effect that was associated with ROS production and G0/G1 cell cycle arrest, but not apoptosis. Moreover, resveratrol suppressed the proliferation of MCF-7 cells by induction of apoptosis as well as cell cycle arrest. Notably, a significant inhibitory effect in the co-treatment of metformin, resveratrol, and cisplatin was observed which was attributed to induction of autophagy-mediated cell death and apoptosis along cell cycle arrest. In conclusion, our results advocate the anti-cancer properties of metformin and resveratrol on MCF-7 cell s via induction of cell cycle arrest. Additionally, synergistic anti-cancer effects of metformin in a triple combination with cisplatin and resveratrol was attributed to induction of autophagy-mediated cell death and apoptosis along cell cycle arrest. Based on our findings it is proposed that patients may benefit from addition of a drug with a safe profile to conventional anticancer therapies.

Pentoxifylline mitigates cholestasis-related cholemic nephropathy.

Aim of the study: Cholestasis is the stoppage of bile flow that primarily affects liver function. On the other hand, kidneys are also severely influenced during cholestasis. Cholestasis-induced kidney injury is known as cholemic nephropathy (CN). There is no precise pharmacological option in CN. Previous studies revealed that oxidative stress plays a crucial role in the pathogenesis of CN. On the other hand, the positive effects of pentoxifylline (PTX) against renal injury with different etiologies have been frequently reported. In the current study, the potential nephroprotective role of PTX in cholestasis-induced renal injury is investigated. Material and methods: Bile duct ligated (BDL) rats were treated with PTX (10, 50, and 100 mg/kg), and renal markers of oxidative stress, urine level of inflammatory cytokines, as well as renal histopathological alterations were monitored. Results: Significant changes in oxidative stress markers were detected in the BDL group. On the other hand, it was found that PTX (10, 50, and 100 mg/kg) significantly ameliorated cholestasis-induced oxidative stress in renal tissue. Renal histopathological changes, including interstitial inflammation, tubular atrophy, fibrosis, and cast formation, were detected in the BDL rats. Moreover, urine pro-inflammatory cytokines [interleukin (IL)-1, IL-9, IL-18, tumor necrosis factor α (TNF-α), and interferon γ (INF-γ)] were significantly increased in the cholestatic animals. PTX (10, 50, and 100 mg/kg, 14 days) significantly ameliorated renal histopathological alterations and urine levels of inflammatory cytokines. Conclusions: These data indicate a potential nephroprotective role for PTX in cholestasis. The effects of PTX on oxidative stress parameters and the inflammatory response could play a primary role in its renoprotective mechanisms.

Efficacy of Honey-based Ophthalmic Formulation in Patients with Corneal Ulcer: A Randomized Clinical Trial.

AIM: The aim of this study was to evaluate the efficacy of honey-based ophthalmic drop in patients with foreign body induced corneal ulcer. BACKGROUND: Honey is traditionally used for skin, mucosal and corneal ulcers. Its use is well studied in human skin and mucosal ulcers and animal model of corneal ulcer with promising effects. METHODS: In this randomized clinical trial, 50 patients with foreign body induced corneal ulcer were allocated to receive 70% sterile honey-based ophthalmic formulation or 0.3% ophthalmic ciprofloxacin, as the standard treatment every 6 hours. All the patients were examined for the size of corneal epithelial defect, corneal infiltration and depth and followed on a daily basis until complete healing. Duration for complete healing was considered as the outcome measure. Smear, culture, antibiogram and minimum inhibition concentration (MIC) tests were performed for honey and ciprofloxacin in all patients. RESULTS: The average durations of complete healing of corneal epithelial defect in the honey and ciprofloxacin groups were 3.88 ± 3.44 vs. 6.32 ± 3.69days, respectively (p=0.020). No significant difference was observed between two groups regarding an average duration of healing of corneal infiltration (8.12 ±1.94 days vs. 8.64±2.15 days, p=0.375). MIC of honey for pseudomonas aeruginosa was 60%w/w, for E.Coli 40% w/w, and for staphylococcus aureus 30% w/w. CONCLUSION: Honey based ophthalmic drop can acceleratethe corneal epithelial defect healing in patients with foreign body induced corneal ulcer, compared to ophthalmic ciprofloxacin as a standard treatment. The study was registered in Iranian registry of clinical trial center (IRCT) with registration number IRCT2015020120892N1.

Synthesis of novel reducing agent for formation of metronidazole-capped silver nanoparticle and evaluating antibacterial efficiency in gram-positive and gram-negative bacteria.

In this study, a new type of silver nanoparticles capped with metronidazolium based ionic liquid is synthesized. By this aim, metronidazole is altered to ionic-liquid type structure with citrate counter ion as reducing agent. The produced reducing agent was characterized using 1HNMR and 13CNMR and FT-IR. The capability of metronidazolium-based reducing agent in formation and capping silver nanoparticles was examined in a chemical reaction. More specifically, synthesized silver nanoparticles were synthesized and capped with metronidazolium-citrate based ionic liquid, while the formation of particles in 48 h was monitored by UV-Vis spectroscopy. Fourier transform infrared spectroscopy showed the presence of capping agents around silver nanoparticles. The amount of metronidazolium and citrate as capping agents was determined by thermal gravimetric analysis. The prepared crystalline structure of silver nanoparticles was proved by X-ray diffraction spectroscopy. PSA analysis and TEM was performed to determine the size of particles. The synthesized silver nanoparticle has the potential to be used as an antibacterial agent in preparation of wound dressing with extra capability and efficacy in aerobic and anaerobic bacterium. In this regard, the antibacterial efficacy of discs from different concentration of silver nanoparticles in calcium alginate medium were evaluated in Gram-negative and Gram-positive bacterium.

Three-component synthesis of chromeno ß-lactam hybrids for inflammation and cancer screening.

Highly diastereoselective synthesis of chromeno ß-lactam hybrids was achieved by an efficient one-pot three-component reaction. With this procedure, the desired ß-lactam products were obtained in good yields and with exclusive cis stereoselection, by combining a variety of benzaldehydes, malononitrile, and either 5,5-dimethylcyclohexane-1,3-dione or 4-hydroxycoumarin in the presence of 1,4-diazabicyclo [2.2.2]octane under reflux conditions. These adducts were structurally characterized on the basis of IR, 1D and 2D NMR spectra, X-ray analysis, H-H COSY and H-C HSQC two-dimensional NMR experiments, and elemental analysis. Each of the synthesized compounds was screened for anti-inflammatory and anticancer activities. ß-Lactams 5b and 8b showed a 53.4 and 19.8 anti-inflammatory ratio, respectively, and 5b appeared more active than the well-known dexamethasone corticosteroid used for the treatment of rheumatoid and skin inflammation. ß-Lactams 5a, 5b, 5e, 5f, 5g, 8c, 8j and 8p also showed good antitumor activity against the SW1116 (colon cancer) cell line without notable cytotoxicity towards the HepG2 control cell line.

Reformulation of Traditional Chamomile Oil: Quality Controls and Fingerprint Presentation Based on Cluster Analysis of Attenuated Total Reflectance-Infrared Spectral Data.

Herbal oils have been widely used in Iran as medicinal compounds dating back to thousands of years in Iran. Chamomile oil is widely used as an example of traditional oil. We remade chamomile oils and tried to modify it with current knowledge and facilities. Six types of oil (traditional and modified) were prepared. Microbial limit tests and physicochemical tests were performed on them. Also, principal component analysis, hierarchical cluster analysis, and partial least squares discriminant analysis were done on the spectral data of attenuated total reflectance-infrared in order to obtain insight based on classification pattern of the samples. The results show that we can use modified versions of the chamomile oils (modified Clevenger-type apparatus method and microwave method) with the same content of traditional ones and with less microbial contaminations and better physicochemical properties.

The highly bioactive molecule and signal substance 6-formylindolo[3,2-b]carbazole (FICZ) plays bi-functional roles in cell growth and apoptosis in vitro.

The maintenance of cellular homeostasis is a complex process that is governed by the receipt of prototypical growth and death signals. The endogenous functions of aryl hydrocarbon receptor (AHR) in cellular homeostasis are not well understood. We aimed to establish whether the disturbance of endogenously activated AHR can influence cell growth, and if so, what mechanism(s) are involved. Cell growth was measured in mouse hepatoma Hepa-1 wild-type and cytochrome P4501A1 (CYP1A1)-deficient c37 cells. In other sets of experiments, HepG2 cells were exposed to different doses of FICZ (0.01nM-1 µM) alone or in combination with 50 nM of the CYP1A1 inhibitor 3'methoxy-4'nitro-flavone (MNF). CYP1A1 enzyme activity, cell viability, oxidative stress, and several endpoints of apoptosis were measured. FICZ treatment at a high concentration or in combination with MNF induced sustained CYP1A1 activity and led to oxidative stress and activation of apoptosis via a mitochondrial-dependent pathway. In comparison with the wild-type Hepa-1 cells, c37 cells lacking CYP1A1 activity proliferated faster in normal medium which contains trace levels of FICZ. Besides, in HepG2 cells, FICZ stimulated cell growth at low concentrations but inhibited cell growth at high concentrations. Based on these findings, we propose that CYP1A1 inhibitors, by increasing the levels of the endogenous ligand FICZ, change the cell growth kinetics and trigger cell death and apoptosis through a mitochondrial-dependent pathway. Since AHR controls multiple cellular functions, a wide range of toxicity can be expected by disturbing its endogenous functions.

Chromatin remodeling by curcumin alters endogenous aryl hydrocarbon receptor signaling.

The aim of this study was to gain more information about the mechanisms that regulate expression of the aryl hydrocarbon receptor (AHR) target gene CYP1A1. Human hepatoma cells (HepG2 and Huh7) and human immortalized keratinocytes (HaCaT) were treated with different concentrations of the dietary polyphenolic compound curcumin (CUR) alone or in combination with the natural AHR agonist 6-formylindolo[3,2-b]carbazole (FICZ). In an earlier study, we described that CUR can activate the AHR indirectly by inhibiting metabolic clearance of FICZ. Here, we measured cell viability, activation of AHR signaling, oxidative stress and histone modifying activities in response to CUR at concentrations ranging from 0.1 to 50 µM. We observed apparent non-linear responses on cell viability and activation of AHR signaling. The CYP1A1 expression and the CYP1A1 enzyme activity in the presence of CUR reflected the histone acetylation efficiency observed in nuclear extracts. At the lowest concentration, CUR significantly decreased histone deacetylase activity and increased the FICZ-induced CYP1A1 activity. In contrast, at the highest concentration, CUR increased the formation of reactive oxygen species, significantly inhibited histone acetylation, and temporally decreased FICZ-induced CYP1A1 activity. The results suggest that CUR can both increase and decrease the accessibility of DNA and thereby influence transcriptional responses to the ligand-activated AHR. This suggestion was supported by the fact that chromatin remodeling treatments with trichostatin A, p300, or 5-aza-dC increased CYP1A1 transcription. We conclude that the AHR-dependent transcriptional efficiency is modified by factors that influence the cellular redox status and the chromatin structure.

An in vivo and in vitro investigation on hepatoprotective effects of Pimpinella anisum seed essential oil and extracts against carbon tetrachloride-induced toxicity.

OBJECTIVES: Protective effects of different extracts and essential oil from Pimpinella anisum L. seeds were examined against carbon tetrachloride (CCl4)-induced toxicity. The parameters such as serum transaminases, lactate dehydrogenase activity, hepatic glutathione content, liver lipid peroxidation and histopathological changes of liver were assessed as toxicity markers. In the in vitro model of this study, markers such as cell viability, cellular reduced and oxidized glutathione and lipid peroxidation in HepG2 cells were evaluated. MATERIALS AND METHODS: Human liver cancer cell line HepG2 and male Sprague-Dawley rats were treated with extracts and essential oil, and markers of hepatotoxicity were investigated. RESULTS: The data revealed that the n-hexane extract, effectively attenuated CCl4-induced toxicity in both in vitro and in vivo models in current investigation. CONCLUSION: As the oxidative stress markers were ameliorated, it might be concluded that anise seed possesses protective effects probably due to its antioxidant constituents.

Prevalence and molecular genotyping of group a rotaviruses in Iranian children.

Rotavirus is the leading cause of acute gastroenteritis in worldwide young children. Effective vaccines to prevent rotavirus infection are currently available, although their clinical use is still limited, and rotavirus still causes many episodes of infantile gastroenteritis, mainly during the winter season. The aim of this study was to evaluate the prevalence of rotavirus infection in children aged <5-years-old who were hospitalised for gastroenteritis. One hundred and sixty-three stool samples from hospitalised children (<5-years-old) complicated with severe diarrhoea, in two hospitals in Jahrom City, Iran were collected from 2009 to 2010. Antigenic prevalence of rotavirus group A was distinguished by enzyme immunoassay. The antigen of group A rotavirus was diagnosed by EIA in 75 of 163 collected samples. The genotype of EIA-positive samples was determined by nested RT-PCR. The frequency of rotavirus genotypes G1, G2, G3, G4 and G9 was 17.33, 13.34, 2.67, 30.66 and 2.67 %, respectively. Also, the frequency of mixed and non-typable genotypes was detected in 2.67 and 30.66 %, respectively. G1/G8 mixed infection was the first of these rotavirus genotypes to be reported in Iran. Detection of high prevalence of group A rotavirus infection in hospitalised children with diarrhoea, and determination of circulating rotavirus genotypes in this region of Iran, provide useful data for formulating effective vaccines; especially for infants less than 5-years-old.