Green synthesis of zinc oxide nanoparticles using novel bacterium strain (Bacillus subtilis NH1-8) and their in vitro antibacterial and antibiofilm activities against Salmonellatyphimurium.

Zinc oxide nanoparticles (ZnO NPs) are used in a range of applications, including food packaging, preservation, and storage. In the current investigation, extracellular green synthesis of ZnO NPs through an simple, eco-friendly, and rapid approach using a novel bacterial strain (Bacillus subtilis NH1-8) was studied. To assess the morphological, optical, and structural properties of ZnO NPs, transmission electron microscopy (TEM), energy-dispersive X-ray (EDX), scanning electron microscopy (SEM), fourier transform infrared (FTIR) spectroscopy, ultraviolet-visible (UV-vis) spectroscopy, and X-ray diffraction (XRD) techniques were carried out. In addition, disk diffusion, minimum bactericidal concentration (MBC), and minimum inhibitory concentration (MIC) methods were performed to determine the antibacterial activity of ZnO NPs. The average size of biosynthesized ZnO NPs was 39 nm, exhibiting semi-spherical, which was confirmed by TEM analyses. The UV-vis spectroscopy exhibited the absorption peak at 200-800nm. The ZnO NPs have shown effective antimicrobial and antibiofilm activities against S. typhimurium. Thus, biosynthesized ZnO NPs could be exploited as a breakthrough technology in the surface coating of food containers and cans to minimize contamination by S. typhimurium.

Eight Weeks of Vitamin C Supplementation Restores the Lost Correlation between Serum Leptin and C-reactive Protein (CRP) in Patients with Type 2 Diabetes; A Randomized, Double-blind, Parallel-group, Placebo-controlled Clinical Trial.

OBJECTIVE: Inflammation is a well-described factor in the pathophysiology of type 2 diabetes mellitus (DM), which has been a suspect in the alteration of correlations between CRP and leptin in patients with type 2 DM. AIM: This study aimed to show the effect of vitamin C as an antioxidant on the correlation of the serum levels of C-reactive protein (CRP) and leptin in patients with type 2 DM. METHODS: We recruited 70 patients with longstanding T2DM and randomly assigned them into two groups; one received 500 mg/day of vitamin C, and the other received a placebo for eight weeks. Both groups were matched regarding baseline characteristics such as age, gender, weight, and diabetic medications. RESULTS: Out of 70 individuals, 57 participants were left in the study. After eight weeks of follow-up, leptin level was significantly increased in the Vitamin C group (MD = 3.48 change = 24%, p-value = 0.001) but did not change in the placebo group. Other markers such as Fasting plasma glucose, HbA1c, Creatinine, uric acid, Urea, cholesterol, HDL, LDL, TG, AST, ALT, insulin, and CRP did not significantly change in both groups (p value > 0.05). The significant changes in the leptin level among the vitamin C group also remained after controlling for age, BMI, Blood pressure (BP), Triglyceride (TG), and cholesterol. Also, the correlation between serum CRP and leptin became significant in the vitamin C group after eight weeks of follow-up but not in the placebo group. (rs = 0.730, p < 0.001 vs. rs = 0.286, p-value = 0.266 in placebo group). CONCLUSION: This study shows vitamin C can restore CRP-leptin correlation in patients with type 2 diabetes and increase serum leptin levels. More studies are needed to clarify the mechanism of this restoration. CLINICAL TRIAL REGISTRATION NUMBER: IRCT20160811029306N1.

Improving sexual dysfunction through guided imagery music (GIM): A clinical trial study.

BACKGROUND: Women with perfect health are strong foundations of a healthy and prosperous family life and suppressing the natural needs of women will have adverse effects on the intimacy and vitality of family members, especially in the field of sexual function. This study aimed to determine the effect of GIM on the level of sexual function in women with sexual dysfunction. MATERIALS AND METHODS: In this cluster randomized trial, which was conducted from 2018 to 2019 in the randomly selected comprehensive health centers of Isfahan, Iran, 72 women of reproductive age (two groups of 36 people) with sexual dysfunction were selected by convenience sampling method, and then, music-guided imagination was performed on the intervention group. No special intervention was performed in the control group. Data collection tools were demographic characteristics questionnaire and a standard questionnaire of the female sexual function index. RESULTS: There was no statistically significant difference in sexual function and demographic characteristics before the intervention between the two groups (P = 0/301). The results demonstrated that the overall score of sexual function in the intervention subjects was better than the control group (P = 0/003). Improvement of sexual function dimensions (desire, arousal, orgasm) was also significant in the intervention group compared to the control group (P < 0.05). CONCLUSION: GIM can be effective in improving women's sexual function. Providing this technique as a low-cost and affordable method is recommended to health experts in private and government clinics. This method can improve the mental health of the family and society.

Prodrug Polymeric Nanoconjugates Encapsulating Gold Nanoparticles for Enhanced X-Ray Radiation Therapy in Breast Cancer.

An optimal radiosensitizer with improved tumor retention has an important effect on tumor radiation therapy. Herein, gold nanoparticles (Au NPs) and drug-containing, mPEG-conjugated CUR (mPEG-CUR), self-assembled NPs (mPEG-CUR@Au) are developed and evaluated as a drug carrier and radiosensitizer in a breast cancer mice model. As a result, cancer therapy efficacy is improved significantly by applying all-in-one NPs to achieve synchronous chemoradiotherapy, as evidenced by studies evaluating cell viability, proliferation, and ROS production. In vivo anticancer experiments show that the mPEG-CUR@Au system improves the radiation sensitivity of 4T1 mammary carcinoma and completely abrogates breast cancer.

Antimicrobial Activity of Silver Nanoparticles Synthesized by the Green Method Using Rhus coriaria L. Extract Against Oral Pathogenic Microorganisms.

Background: Oral health is part of general health. Dental caries is the most common chronic disease worldwide. Considering the significance of plaque control, complications of chemical agents, and the optimal antimicrobial efficacy of nanoparticles, this study aimed to assess the antimicrobial activity of silver nanoparticles (AgNPs) synthesized by the green method using Rhus coriaria L. extract against oral pathogenic microorganisms. Methods: In this in vitro experimental study, Rhus coriaria fruit was dried at room temperature. It was then ground, and its aqueous extract was obtained by the maceration technique. The effects of AgNPs synthesized by the green method in different concentrations were evaluated against Enterococcus faecalis (E. faecalis), Streptococcus mutans (S. mutans), Streptococcus sobrinus (S. sobrinus), Lactobacillus acidophilus (L. acidophilus), and Streptococcus salivarius (S. salivarius) using the well-plate technique. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were also calculated. Data were analyzed by the Wilcoxon test, Kruskal-Wallis test, and Mann-Whitney test. Results: The MIC values were 1024 µg/mL for S. mutans and E. faecalis, and 512 µg/mL for S. sobrinus, S. salivarius, and L. acidophilus. The resistance of S. mutans and E. faecalis was higher than that of S. sobrinus, S. salivarius and L. acidophilus. According to the growth inhibition zones and MBC test results, S. salivarius had the highest resistance to AgNPs followed by L. acidophilus, S. sobrinus, S. mutans, and E. faecalis. Conclusion: AgNPs synthesized by the green method using Rhus coriaria extract was effective against oral pathogenic microorganisms. Thus, they may be used in the formulation of mouthwash and toothpaste.

Efficacy and expenses of succimer vs. d-penicillamine plus garlic in the treatment of lead poisoning: a retrospective cross-sectional study.

PURPOSE: Lead Poisoning is a major health problem in Iran. We aimed to compare efficacy of a standard regimen (Succimer) with that of a low-priced combination of D-penicillamine and Garlic in outpatients with lead poisoning. METHODS: In this retrospective cross-sectional study, year-long clinical files of outpatients with lead poisoning in two referral toxicology clinics in Mashhad, Iran were reviewed. A total of 79 patients (all men), received either Succimer or a combination of D-penicillamen plus garlic (DPN + Gar), for 19 and 30 days, respectively. Clinical and laboratory data, including blood lead level (BLL), were analyzed and treatment expanses were compared between the two regimens. RESULTS: Of 79 male patients, 42 were treated by DPN + Gar and 37 received Succimer. Mean BLL of DPN + Gar group before treatment (965.73 ± 62.54 µg/L) was higher than that of the Succimer group (827.59 ± 24.41) (p < 0.001). After treatment, BLL in both groups significantly reduced to 365.52 ± 27.61 µg/L and 337.44 ± 26.34 µg/L, respectively (p < 0.001). The price of a 19-day treatment with Succimer was approximately 28.6 times higher than a one-month course of treatment with garlic plus DPN. None of the treatments caused serious side effects in the patients. CONCLUSION: Combination therapy with DPN + Gar is as effective as Succimer in Pb poisoning, while treatment with Succimer is significantly more expensive.

Iron oxide and gold bimetallic radiosensitizers for synchronous tumor chemoradiation therapy in 4T1 breast cancer murine model.

The development of highly integrated multifunctional nanomaterials with a superadditive therapeutic effect and good safety is an urgent but challenging task in cancer therapy research. The present study aims to design a nanoplatform that offers the opportunity to enhance antitumor activity while minimizing side effects. Given the Au-mediated X-ray radiation enhancement and the ability of Fe-based nanomaterials to create reactive oxygen species (ROS) and DNA damage, we anticipated that bimetallic Fe3O4-Au heterodimer would bring strong radiosensitizing capacity. Fe3O4-Au heterodimer surface was covered with bovine serum albumin (BSA) to achieve good surface functionality, stability and prolonged blood circulation. Folic acid (FA) moieties were added to the nanoformulation to increase tumor-homing, specificity and uptake. Finally, curcumin (CUR) was incorporated into the nanoparticle to function as a natural anticancer agent. The integration of all these components has yielded a single nanoplatform, Fe3O4-Au-BSA-FA-CUR, capable of successfully fulfilling the mission of superadditive cancer therapy to avoid the risks of organ removal surgery. The efficacy of the proposed nanoplatform was investigated in vitro and in vivo. High radiosensitizing ability, X-ray-induced ROS generation and DNA damage, and good biocompatibility were demonstrated through in vitro experiments. Also, the administration of Fe3O4-Au-BSA-FA-CUR with X-ray irradiation completely eradicated the tumor without any mortality and toxicity in healthy tissues in vivo. Our results highlight the potential of CUR-loaded Fe3O4-Au-BSA-FA heteronanostructure to enable synergistic localized radiochemotherapy and open up a new door to attractive possibilities that warrant further exploration.

Effects of Zataria multiflora essential oil on the germinative cells of Echinococcus granulosus.

BACKGROUND: Novel and more efficient compounds are urgently required for medical treatment of cystic echinococcosis (CE). Germinative cell culture of Echinococcus granulosus could be used for anti-echinococcosis agent tests and other biological studies on CE. This study was performed to establish an in vitro cell culture model for E. granulosus germinative cells and to evaluate the lethal effect of Zataria multiflora essential oil (ZMEO) on the cultured cells. METHODS: The inner surface of germinal layers of CE cysts was scraped, and the obtained materials were trypsinized to obtain a suspension of single germinative cells. Medium 199 was used as the basic culture medium and was supplemented with fetal bovine serum, 2-mercaptoethanol, L-cysteine, L-glutamine, glucose, sodium pyruvate, hydatid fluid, amphotericin B and antibiotics. The cells were cultured at a concentration of 104 cells/ml of culture medium and incubated at 37 °C. The culture medium was replaced every 7 days. Chemical composition of ZMEO was identified by GC-MS analysis. ZMEO was tested at concentrations of 0.5-8 mg/ml. Viability of the cells was assessed by trypan blue exclusion assay. RESULTS: A significant increase in the cell number was evident at 20, 30 and 45 days after cultivation. At 45 days of cultivation, the number of cells was approximately five-fold higher than on the first day. In GC-MC analysis, carvacrol, p-cymene, g-terpinene and thymol were found to be the main compounds of ZMEO. The lethal effect of ZMEO on the germinative cells at concentrations of 6, 7 and 8 mg/ml was 100% after 60, 25 and 7 min of exposure, respectively. CONCLUSIONS: At 45 days of cultivation, the cell concentration was suitable for the desired in vitro experiments. A high lethal effect of ZMEO on the germinative cells of E. granulosus may be considered an opportunity for the introduction of a novel, more effective and safer therapeutic agent for treatment of CE using an herbal product.

Evaluation of Vitamin D3 and Calcium Deficiency after Recovery from Extensive Burn.

BACKGROUND: Previous studies in pediatric populations have demonstrated that vitamin D deficiency is common in patients with large burns. The aim of the current comparative study was to investigate the serum level of vitamin D in patients with large burns [>20% total body surface area (TBSA)] after 6 months of therapy. METHODS: This case control study was conducted during 6-month period from 2017 to 2018 in Amiralmomenin Hospital, Shiraz, Iran. Forty two patients with large burns (>20% TBSA) and at least 6 months' post-burn period were enrolled. Also, 42 healthy and age and sex matched controls from those referring for routine check-ups were included for comparison. None of the patients and controls received vitamin D supplements. The serum level of calcium (Ca), parathormone (PTH) and vitamin D were compared between the groups. RESULTS: There was no significant difference between the two study groups regarding the baseline characteristics including the age (p=0.085), gender (p=0.275) and duration of sun exposure (p=0.894). We found that those with major burns had significantly higher serum levels of PTH (50.48±26.49 vs. 33.64±15.80; p=0.001). In addition, the serum levels of vitamin D were significantly lower in burn patients compared to healthy controls (18.15±9.18 vs. 31.43±16.27; p<0.001). CONCLUSION: Major burns (≥20% TBSA) are associated with increased serum levels of PTH and decreased serum levels of vitamin D. However, serum levels of calcium are not affected by major burns.

Comparison of the efficacy of oral fenugreek seeds hydroalcoholic extract versus placebo in nonalcoholic fatty liver disease; a randomized, triple-blind controlled pilot clinical trial.

OBJECTIVES: The aim of this study is to investigate the therapeutic property of hydroalcoholic extract of Fenugreek seeds in nonalcoholic fatty liver disease (NAFLD) in adult patients. METHODS: This randomized, placebo-controlled, parallel trial was conducted from November 2014 to June 2017. Patients aged between 18 and 70 years old with confirmed NAFLD were recruited from the Motahhari clinic, affiliated to Shiraz University of Medical Sciences, Iran. Participants either received 1 g hydroalcoholic extract of Fenugreek seeds or placebo daily for 3 months. The primary outcomes were changes in serum alanine transaminase and FibroScan controlled attenuation parameter score. Secondary outcome measures were changes in other laboratory data, liver stiffness measure, liver steatosis percent, and anthropometric variables. Participants were randomly assigned to the groups using blocked randomization method. Participants, investigators, and statistician were blinded to treatments allocation. RESULTS: After screening eighty patients, thirty patients met the inclusion criteria and were divided into two groups (1:1). After 3 months, two and four patients did not complete the trial in Fenugreek and placebo group, respectively. The changes in the anthropometrics, laboratories and FibroScan measurements were not statistically significant between the two groups. CONCLUSION: The evidence to prove the efficacy of the Fenugreek seeds' hydroalcoholic extract in NAFLD was not strong enough; hence, further experiments are still needed to assess the possible efficacy of Fenugreek on the treatment of NAFLD.

Effects of oral butyrate and inulin supplementation on inflammation-induced pyroptosis pathway in type 2 diabetes: A randomized, double-blind, placebo-controlled trial.

PURPOSE: Pyroptosis, a form of inflammatory programmed cell death, is activated in diabetic patients. This study was conducted to investigate the effects of daily consumption of sodium butyrate (NaBut) and high-performance (HP) inulin supplementation, individually or in combination, on the expression of pyroptosis-related genes, microRNA (miR) 146a-5p, miR-9-5p and biomarkers of oxidative stress in patients with type 2 diabetes (T2DM). METHODS: In this study, we conducted a randomized, double-blinded, placebo-controlled clinical involving sixty patients with type 2 diabetes. Participants received 600 mg/d of NaBut (group A), 10 g/d of HP inulin (group B), 600 mg/d of NaBut + 10 g/d of HP inulin (group C) or placebo (group D) for 45 consecutive days. We assessed the pyroptosis-related genes mRNA expression in peripheral blood mononuclear cells (PBMCs), as well as the plasmatic levels of miR-146a and miR-9 before and after the intervention. Moreover, blood samples of the patients at baseline and following the intervention were tested for total antioxidant capacity (TAC), superoxide dismutase (SOD) and catalase levels using enzyme-linked immunosorbent assay (ELISA). This study was registered on the Iranian Registry of Clinical Trials website (identifier: IRCT201605262017N29; https://www.irct.ir/). RESULTS: Following butyrate supplementation, the relative expression levels of TLR2/4, NF-κB1, Caspase-1, NLRP3, IL-1ß & IL-18 were significantly downregulated (p < 0.05). Furthermore, butyrate and concomitant use of butyrate and inulin caused a significant increase in the fold change of miR-146a and miR-9 compared with the placebo group (p < 0.05). Interestingly, the changes in total antioxidant capacity (p = 0.047) and superoxide dismutase (p = 0.006) were significantly increased after butyrate and concomitant use of butyrate and inulin supplement, respectively. CONCLUSION: In summary, the change in expression level of miR-146a-5p and miR-9-5p due to butyrate supplementation may have a pivotal role in alleviating of diabetes via inhibiting pyroptosis by targeting TLR2 and NF-κB1. These microRNAs might be considered as potential therapeutic targets in the treatment of type 2 diabetes but further researches is required to prove the link.

Comparison of the immediate analgesic effect of perpendicular needling and transverse needling at SP6 in patients with primary dysmenorrhea: Study protocol for a randomized controlled trial.

BACKGROUND: Acupuncture has been widely used to treat primary dysmenorrhea (PD) with satisfactory outcomes. Sanyinjiao (SP6) is the most commonly used acupoint for PD. Different needling techniques may influence the effect of SP6, and its underlying mechanism needs to be explored. This randomized controlled parallel trial is designed to evaluate the immediate analgesic effect and hemodynamic responses in uterine arterial blood flow of perpendicular needling and transverse needling at SP6 in patients with PD of cold-dampness stagnation pattern using color doppler ultrasonography. METHODS: Forty-eight patients who meet inclusion criteria will be randomized in a ratio of 1:1 to either perpendicular needling or transverse needling groups. Every participant will receive 1 session of acupuncture treatment for 10 minutes at bilateral SP6. In the perpendicular needling group, needles will be inserted vertically 1 to 1.2 cun and will be manipulated to achieve needling sensation. In transverse needling group, the needles will be inserted transversely 1 to 1.2 cun toward the abdomen without any manipulation to avoid needling sensation. Color doppler ultrasonography will be performed before, during, and after needling. The primary outcome measure is visual analog scale for pain. The secondary outcome measures include the uterine artery blood flow changes by measuring pulsatility index, resistance index values, and ratio of systolic peak and diastolic peak, the Hamilton anxiety scale, blood pressure, and heart rate. Adverse events in both groups also will be recorded. DISCUSSION: This trial will be the first study protocol designed to explore the influence of needling techniques on the analgesia effect of solo acupoint and its hemodynamic responses for PD. It will promote more widespread awareness of the benefits of using suitable needling techniques in acupuncture clinical setting and provide a further explanation of the underlying hemodynamic mechanism. TRIAL REGISTRATION: This study protocol was registered at the Chinese clinical trial registry (ChiCTR1900026051).

Docosahexaenoic acid suppresses migration of triple-negative breast cancer cell through targeting metastasis-related genes and microRNA under normoxic and hypoxic conditions.

There is insufficient evidence with respect to the effect of the standard anticancer therapeutic agents as well as common dietary supplements on the expression of such genes and microRNAs (miRNAs). Therefore, this study was aimed to study the effect of applying linoleic acid (LA) and docosahexaenoic acid (DHA) fatty acids alone or combined with Taxol on the expression of the matrix metalloproteinase (MMP)-9, MMP-2, vimentin, and talin2 genes, tumor-suppressor miR-194 and, onco-miR-106b in triple-negative breast cancer cell line, known as MDA-MB-231. MDA-MB-231 as metastatic breast cancer cell line was cultured and treated using 0.3 µM Taxol, 100 µM DHA, and 50 µM LA for 24 hours, alone or combined with Taxol under the normoxic and hypoxic conditions. Cells were harvested, after RNA extraction and complementary DNA synthesis, analysis of the expression levels of the studied genes and miRNAs was done through the use of the quantitative real-time polymerase chain reaction (qRT-PCR). Wound healing assay and Western blot analysis were also performed for confirmation. The results of qRT-PCR showed that treating the MDA-MB-231 cells with DHA caused an increase in the miR-194 expression and a decrease in the miR-106b expression, leading to the downregulation of the MMP-2 and MMP-9, and vimentin, and upregulation of the talin2 under the normoxic and hypoxic conditions. The results of the wound healing scratch assay revealed that the administration of the DHA and the DHA-Taxol combination caused the repression of cell migration in comparison with the control groups under the normoxic and hypoxic conditions. The results of the Western blot analysis demonstrated that DHA and the DHA-Taxol combination caused an increase in the expression of the talin2 protein rather than the control cells under both normoxic and hypoxic conditions. This study showed that DHA has significant antimetastatic effects against the triple-negative breast cancer cells. DHA could serve as a promising supplementation for suppressing the breast cancer cell migration, especially under the hypoxic condition.

Non-Carcinogenic Health Risk Assessment due to Fluoride Exposure from Tea Consumption in Iran Using Monte Carlo Simulation.

Excessive intake of fluoride can cause adverse health effects. Consumption of tea as a popular drink could be a potential source of fluoride exposure to humans. This research aimed to evaluate the fluoride concentration in tea among the Iranian people using the available data in the literature and to assess the health risk related to the consumption of tea in men, women, and children. The health risk assessment was conducted using the chronic daily intake and hazard quotient according to the approach suggested by the Environmental Protection Agency. The fluoride content in published studies varied noticeably, ranging from 0.13 to 3.27 mg/L. The results revealed that the hazard quotient (HQ) in age groups of women (21-72 years) and children (0-11 years) was within the safe zone (HQ < 1) which showed that there was no potential of non-carcinogenic risk associated with drinking tea in these groups. However, in one case of the men (21-72 years), the HQ > 1 which shows a probable risk of fluorosis. The order of non-carcinogenic health risks in the studied groups was in the order of men > women > children. The results of this can be useful for organizations with the responsibility of human health promotion.

Anti-tumor Effect of Quercetin Loaded Chitosan Nanoparticles on Induced Colon Cancer in Wistar Rats.

Purpose: This study was aimed to evaluate the site-specific drug delivery of 5-FU with chitosan (CS) as a carrier and quercetin (Qu) against induced colon cancer in Wistar rats. Methods: Cross-linked CS-Qu nanoparticles (NPs) were prepared by ionotropic gelation method. Physicochemical characterization of NPs was performed by Fourier-transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), in vitro drug release, and drug loading efficiency (LE). 1, 2-Dimethylhydrazine (DMH) and dextran sulfate sodium (DSS) were applied to induce adenocarcinoma tumors on inbred male Wistar rats' colon. The treatment group of rats was administered through enema with NPs dispersion. Hematoxylin and eosin staining were performed to the histopathological examination of tumors. Results: Zeta potential and particle size for NPs were +53.5 ± 5 mV and 179 ± 28 nm, respectively. About 96% Qu LE was obtained with a maximum release of 5.63 ±1.59% and 4.62 ± 1.33% after 24 hours in PB solution with pH values of 6 and 7.4, respectively. The numbers of 8 to 21 tumors were observed in all rats administered with DMH and DSS. Significantly decreasing of microvascular density and mitosis count was detected in the treatment group in comparison with cancerous group (P = 0.032 for the former compared to P = 0.016 for the later), respectively. Furthermore, the treatment group showed a high apoptosis rate (P = 0.038). Conclusion: The developed Qu-loaded CS NPs were good candidates for site-specific and sustained drug release in enema treatment. Decreasing of microvascular density and mitosis count, along with increasing the apoptosis percent in the treatment group proved that the NPs could have promising results in site-specific and sustained drug delivery against colorectal cancer.

Photodynamic therapy using zinc phthalocyanine with low dose of diode laser combined with doxorubicin is a synergistic combination therapy for human SK-MEL-3 melanoma cells.

Chemotherapy is a generally used anticancer strategy for melanoma and it may have improved outcomes in combination with other approaches. One such strategy is photodynamic therapy (PDT), where a photosensitizer (PS) generates reactive oxygen species (ROS) after illumination of target cells. Interestingly, in low doses and high doses of light sources, special cellular responses can be induced. Regarding this fact, in this study, the combination of zinc phthalocyanine (ZnPc)-PDT and Doxorubicin (DOX) was applied at low and high dose of diode laser to treat SK-MEL-3 cells. Cytotoxic effects were determined by MTT assay for assessment synergistic effects were estimated by calculation of Combination Index (CI); that synergistic effects were observed in most groups. In low dose of laser irradiation higher synergism effects were observed. Significant changes of ROS were not observed with combinations, but autophagy, subG1 and G2/M phase cell cycle arrest, decreased cell migration ability and apoptosis induction were significantly increased compared to either treatment alone. The expression of caspase-8, -9, -3 and Bcl-2 genes revealed caspase-dependent apoptosis in all groups. Moreover, ZnPc-PDT and chemo-PDT down-regulated the expression of MMP-9 and Vimentin genes that impaired cell migration. In conclusion, it can be suggested that pre-treatment with ZnPc-PDT has high effects to sensitize SK-MEL-3 cells to DOX, in particular with low dose of diode laser.

Photodynamic therapy for cancer: Role of natural products.

Photodynamic therapy (PDT) is a promising modality for the treatment of cancer. PDT involves administering a photosensitizing dye, i.e. photosensitizer, that selectively accumulates in tumors, and shining a light source on the lesion with a wavelength matching the absorption spectrum of the photosensitizer, that exerts a cytotoxic effect after excitation. The reactive oxygen species produced during PDT are responsible for the oxidation of biomolecules, which in turn cause cell death and the necrosis of malignant tissue. PDT is a multi-factorial process that generally involves apoptotic death of the tumor cells, degeneration of the tumor vasculature, stimulation of anti-tumor immune response, and induction of inflammatory reactions in the illuminated lesion. Numerous compounds with photosensitizing activity have been introduced commercially. Although many papers have been published with regard to PDT in the last decade, there has been relatively little focus on natural medicinal plant extracts and compounds derived therefrom. Herbal plants and their extracts are natural substances, and in comparison with synthetic chemicals are considered "green". This review focuses on the different mechanisms of PDT and discusses the role of various plant extracts and natural compounds either alone or in combination for carrying out PDT on different types of cancers.