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Abstract Background Developing a drug delivery system that can transport a higher concentration to the target cells can improve therapeutic efficacy. This study aimed to develop a novel delivery system for acetyl-11-keto-beta-boswellic Acid (AKBA) using chitosan-sodium alginate–calcium chloride (CS-SA-CaCl2) nanoparticles. The objectives were to evaluate the antiproliferative activity of these nanoparticles against colorectal cancer (CRC) cells and to improve the bioavailability and therapeutic efficacy of AKBA. Results With an extraction efficiency of 12.64%, AKBA was successfully extracted from the gum resin of B. serrata. The nanoparticle delivery system exhibited superior cytotoxicity against HT29 cells compared to free AKBA, AKBA extract (BA-Ex), and 5-FU. Furthermore, the nanoformulation (nano-BA-Ex) induced apoptosis in HT29 cells more effectively than the other treatments. In vivo results showed that nanoformulation inhibited chemically induced colon tumorigenesis in mice and significantly reduced the number of aberrant crypt foci (ACFs). Conclusions The developed CS-SA-CaCl2 nanoparticles loaded with AKBA extract exhibit potential as a potent drug delivery mechanism for the colorectal cancer model. Nano-BA-Ex is a promising strategy for enhancing the solubility, bioavailability, and therapeutic efficacy of BA derivatives. With its multiple effects on cancer cells and controlled drug release through nanocapsules, nano-BA-Ex stands out as a compelling candidate for further preclinical and clinical evaluation in CRC therapy.

Globally, hepatic cancer ranks fourth in terms of cancer-related mortality and is the sixth most frequent kind of cancer. Around 80% of liver cancers are hepatocellular carcinomas (HCC), which are the leading cause of cancer death. It is well known that HCC may develop resistance to the available chemotherapy treatments very fast. One of the biggest obstacles in providing cancer patients with appropriate care is drug resistance. According to reports, more than 90% of cancer-specific fatalities are caused by treatment resistance. By binding to the 3'-untranslated region of target messenger RNAs (mRNAs), microRNAs (miRNAs), a group of noncoding RNAs which are around 17 to 25 nucleotides long, regulate target gene expression. Moreover, they play role in the control of signaling pathways, cell proliferation, and cell death. As a result, miRNAs play an important role in the microenvironment of HCC by changing immune phenotypes, hypoxic conditions, and acidification, as well as angiogenesis and extracellular matrix components. Moreover, changes in miRNA levels in HCC can effectively resist cancer cells to chemotherapy by affecting various cellular processes such as autophagy, apoptosis, and membrane transporter activity. In the current work, we narratively reviewed the role of miRNAs in HCC, with a special focus on tumor microenvironment and drug resistance.

Background. Helicobacter pylori (H. pylori), a widespread bacterial pathogen, is associated with various gastrointestinal diseases, including gastric cancer. Statins, widely prescribed cholesterol-lowering agents, have demonstrated pleiotropic effects, including potential antimicrobial properties. This in vitro study investigated the direct antibacterial effects of three clinically approved statins, simvastatin, atorvastatin, and rosuvastatin, against H. pylori isolates. Methods. H. pylori strains were isolated from gastric biopsies of dyspeptic patients and identified by microbiological techniques. The minimum inhibitory concentrations (MICs) of statins were determined using the agar dilution method, and their antimicrobial activity was evaluated by the disc diffusion method using different concentrations of simvastatin, atorvastatin, rosuvastatin, tetracycline, and amoxicillin. Scanning electron microscopy (SEM) was employed to examine the morphology of H. pylori cells. Results. The minimum inhibitory concentration (MIC) values (μg/mL) of atorvastatin, rosuvastatin, simvastatin, tetracycline, and amoxicillin against H. pylori were 240 ± 20, 450 ± 20, 460 ± 15, 155 ± 30, and 140 ± 20, respectively. In the disc diffusion assay, atorvastatin and rosuvastatin produced significantly larger inhibition zones compared to simvastatin at all concentrations tested (p

Background. Copper is an essential trace element found in the human body in an oxidized (Cu II) and reduced (Cu I) form. It plays a crucial role in the integrity and function of proteins and enzymes. Short-term and long-term exposure to copper can result in harmful effects and lead to clinical manifestations in multiple bodily systems, including the gastrointestinal tract, liver, kidneys, eyes, respiratory, cardiovascular, central nervous, endocrine, and hematopoietic systems. Objective. The purpose of this study is the importance of early recognition and diagnosis of copper poisoning immediate and necessary measures and the use of chelators. Materials and Methods. In this review article, authors from Pub Med, Scopus, and a toxicologic emergencies reference book from 1996 to 2024 are used. Result. An excessive increase in copper level produces reactive oxygen species that can cause lipid peroxidation in cell membranes, direct oxidation of proteins, and the breakdown of DNA and RNA molecules. All of these can generally be reasons for cell death. Conclusion. Assessing levels of copper in whole blood, free serum copper, 24-hr urine copper, liver biopsy for copper concentration, and ceruloplasmin play a crucial role in the diagnosis. The blood copper concentration is directly related to the severity of poisoning. Treatment for copper poisoning typically involves removing the source of exposure and administering medications to help remove the excess copper from the body. Supportive care for copper intoxication usually includes managing vomiting, correcting fluids and electrolytes, and stabilizing vital signs. Chelators like D-penicillamine, succimer, trientine, tetrathiomolybdate, and PBT-2 have been utilized in treatment.

Introduction: Nifedipine (NF) is a calcium channel blocker that accelerates wound healing and subsequently relieves pain and discomfort. The aim of the present study was to investigate the local effect of this drug on the wound-healing process of the palate. Materials & Methods: In this triple-blind clinical trial study, 31 patients who were referred to the Periodontology Department of Babol Dental School (14 in the experimental group and 17 in the control group) were examined. They were candidates for gingival surgery and needed a palate transplant. Mucotom was used to create identical wounds in the palate (transplant donor). After a free gingival grafting, the active ingredient of 0.3% NF was applied as a mucosal adhesive (made of chitosan) in the area of the graft (palate). Patients were examined and recorded on days 2, 4, 7, 14, and 30 after surgery for wound closure and healing criteria (Landry & Manchester scar scale) and pain (VAS). Sutures were removed on day 7 of the study. Data were analyzed with SPSS 20 and chi-square, Kruskal-Wallis and Mann-Whitney tests. The significance level was set at 0.05. Results: Based on Landry and Manchester criteria, the wound healing process in the two groups was not significant (p=0.125). There was no significant difference between mean wound size reduction and VAS in both treatment and control groups (p=0.253). Conclusion: Topical NF has no effect on the natural process of healing oral mucosal ulcers and reducing pain.

Statement of the Problem: Continuous use of chemical agents to reduce the number of cariogenic bacteria leads to adverse effects; therefore, in recent years, many studies have focused on plant-based substances. Purpose: This study explores the antibacterial effects of Mentha Longifolia (M. longifolia) essential oil on Streptococcus mutans (S. mutans), Streptococcus sobrinus (S. sobrinus), and Lactobacillus as cariogenic microorganisms and determines the compounds in it. Materials and Method: In this experimental study, S. mutans, S. sobrinus, and Lactobacillus isolates were collected from the saliva samples of five children with severe early childhood caries (S-ECC). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of M. longifolia essential oil were determined by Broth microdilution method. Chlorhexidine 0.2% and phosphate-buffered normal saline (pH= 7.0) were used as positive and negative controls, respectively. The chemical composition of M. longifolia essential oil was evaluated by gas chromatography-mass spectrometry. The data were analyzed with a paired t-test and the p below 0.05 was considered significant. Results: The MIC and MBC ratios for S. mutans were 3.12% and 6.25%, for S. sobrinus were 6.25% and 12.5%, ​​and Lactobacillus were 3.12% and 6.25%, respectively. Chemical analysis of M. longifolia essential oil showed that 34 various compounds. Piperitone oxide (27.59%), Transcariophylline (14.55%), and 2-cyclohexane-1-one (12.24%) were the major constituents. Conclusion: M. longifolia essential oil has both growth inhibitory and bactericidal effects on all the three species of bacteria. This antibacterial effect was similar against S. mutans and Lactobacillus, which was greater than S. sobrinus, thus, it can be used as a supplementary for caries prevention compounds.

Oxaliplatin (cyclohexane-1,2-diamine; oxalate; platinum [2+]) is a third-generation chemotherapeutic drug with anticancer effects. Oxaliplatin has a role in the treatment of several cancers. It is one of the few drugs which can eliminate the neoplastic cells of colorectal cancer. Also, it has an influential role in breast cancer, lung cancer, bladder cancer, prostate cancer, and gastric cancer. Although oxaliplatin has many beneficial effects in cancer treatment, resistance to this drug is in the way to cure neoplastic cells and reduce treatment efficacy. microRNAs are a subtype of small noncoding RNAs with ∼22 nucleotides that exist among species. They have diverse roles in physiological processes, including cellular proliferation and cell death. Moreover, miRNAs have essential roles in resistance to cancer treatment and can strengthen sensitivity to chemotherapeutic drugs and regimens. In colorectal cancer, the co-treatment of oxaliplatin with anti-miR-19a can partially reverse the oxaliplatin resistance through the upregulation of phosphatase and tensin homolog (PTEN). Moreover, by preventing the spread of gastric cancer cells and downregulating glypican-3 (GPC3), MiR-4510 may modify immunosuppressive signals in the tumor microenvironment. Treatment with oxaliplatin may develop into a specialized therapeutic drug for patients with miR-4510 inhibition and glypican-3-expressing gastric cancer. Eventually, miR-122 upregulation or Wnt/β-catenin signaling suppression boosted the death of HCC cells and made them more sensitive to oxaliplatin. Herein, we have reviewed the role of microRNAs in regulating cancer cells’ response to oxaliplatin, with particular attention to gastrointestinal cancers. We also discussed the role of these noncoding RNAs in the pathophysiology of oxaliplatin-induced neuropathic pain.

Multiple myeloma (MM) produces clonal plasma cells and aberrant monoclonal antibody accumulation in patients’ bone marrow (BM). Around 1% of all cancers and 13% of hematological malignancies are caused by MM, making it one of the most common types of cancer. Diagnostic and therapeutic methods for managing MM are currently undergoing extensive research. MicroRNAs (miRNAs) are short noncoding RNAs that reduce or inhibit the translation of their target mRNA after transcription. Because miRNAs play an influential role in how myeloma develops, resources, and becomes resistant to drugs, miRNA signatures may be used to diagnose, do prognosis, and treat the myeloma response. Consequently, researchers have investigated the levels of miRNA in plasma cells from MM patients and developed tools to test whether they directly impacted tumor growth. This review discusses the latest discoveries in miRNA science and their role in the development of MM. We also emphasize the potential applications of miRNAs to diagnose, prognosticate, and treat MM in the future.

Introduction: E. coli is one of the failure factors in the pulpectomy of primary and permanent teeth. It is also responsible for many infectious diseases in Humans. This study aimed to determine antibacterial effect of arginine, protamine, aqueous extract of green tea, and Aloe vera against Escherichia coli (E. coli). Material & Methods: Aqueous extract of green tea, Aloe vera, and protamine with a concentration of 400 mg/ml, and arginine at a concentration of 160 mg/ml were used in this experimental study. E. coli was cultured on Mueller-Hinton broth and minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the test materials against this microorganism was determined using micro-dilution test. Sodium hypochlorite 2.5% was used as a positive control. (Ethic code: 9643822) Findings: It was found that protamine had the highest antibacterial activity (with MIC and MBC 0.62 mg/mL) and aqueous extract of green tea showed the lowest antibacterial activity against E. coli (with MIC100 mg/ml and MBC 200 mg/ml). Positive control (sodium hypochlorite 2.5%) showed better antibacterial activity against E. coli compared to other test materials. Discussion & Conclusion: Apart from sodium hypochlorite, among the tested materials, protamine had the maximum effect and aqueous extract of aloe vera, arginine, and aqueous extract of green tea showed the lowest antibacterial effect against E. coli., respectively.

5-Fluorouracil (5FUra) is the third most popular chemotherapeutic component employed to treat solid tumors. In the present study, we aimed to appraise the silymarin (SM) and silymarin nanoemulsion (SMN) effect on 5FUra-induced gastrointestinal toxicity in adult male rats. A total of 30 male Wistar rats were divided into 6 groups including the control (Crl) group, and groups treated with SMN (5 mg.kg−1), SM (5 mg.kg−1), 5FUra + SMN (5 mg.kg−1), and 5FUra + SM (5 mg.kg−1) by IP injection for 14 days. And gastrointestinal toxicity was induced by a single intraperitoneal (IP) injection of 5FUra (100 mg.kg−1) for the last group in the study. Treating rats with SM and SMN diminished elevating malondialdehyde (MDA) levels, and improved total antioxidant capacity (TAC) levels. Also, the intensity of mRNA expression of interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-α) caused by 5FUra in the gastrointestinal tissue tract, and macroscopic oral ulcerations decreased, ass well as weight loss was prevented, particularly in the SMN group. Moreover, in the microscopic scope, there were significant improvements in the levels of hyperemia, hyaline, and inflammatory cell infiltration in the tongue, esophagus, and intestinal tissues in the FUra + SMN and FUra + SM groups compared to 5FUra. Hence, treatment with SM and SMN reduced oxidative stress, histopathological degeneration, and gene expression of inflammatory markers in the gastrointestinal tract. According to the results, treatment with SM and SMN markedly decreases the gastrointestinal toxicity caused by 5FUra.

Statement of the Problem: Molar teeth with furcation involvement are one of the most common problems in patients with periodontal disease. Regeneration methods are of the most controversial treatment strategies for these lesions. Purpose: The purpose of this study was to determine the effect of plasma rich in growth factors (PRGF) with 1.2% Atorvastatin (ATV) in the treatment of furcation involvement of mandibular molars. Materials and Method: The present randomized clinical trial was conducted on 15 patients with moderate periodontitis and class II furcation involvements; 24 defects were located in four groups of six, including debridement, ATV1.2%, PRGF, PRGF with ATV1.2%. The parameters of vertical probing depth (VPD), vertical clinical attachment level (VCAL), gingival index (GI), horizontal probing depth (HPD) and gingival recession (GR) were measured at baseline (T0), immediately before surgery (T1), 3 (T2), and 6 (T3) months after surgery. Moreover, the bone conditions were evaluated by digital subtraction radiography before and six months after surgery. Data were analyzed using SPSS23 software. Results: No significant difference in radiographic parameters was observed among the groups (p= 0.08). There was no significant difference in the mean levels of VPD, VCAL and HPD among the groups at different times (p

Background: Amongst the chemical warfare agents, blistering (vesicant) agents can be significant materials. The most important agent in this group is sulfur mustard (mustard gas) which is known as “King of chemical warfare (CW) agents “. Exposure to this agent, seriously causes damages in several organs, such as the eyes. This article reviews the ophthalmological aspects of sulfur mustard with reference of its management. Methods: A wide-ranging search in PubMed databases, Thomson Reuters and Scopus was done and different aspects of chemical properties of sulfur mustard, its mechanism of action and effects on eyes, clinical finding, diagnostic evaluation, initiate actions, pharmaceutical and surgical interventions was reported. Results: Sulfur mustard can alkylate DNA and RNA strands and break down structures of protein and lipid of cell membrane. This may impair cell energy production, and leads to cell death. Exposure to sulfur mustard, therefore, causes such problems for organs, including irreversible damage to the eyes. Conclusion: Understanding the mechanism of the sulfur mustard effect and the early training in prevention injuries will cause fewer complications and damage to organs, including the eyes. Washing the eyes with tap water or eyewash solutions, using mydriatic drops, anti- inflammatory drugs, matrix metalloproteinase inhibitors and antibiotics may help to the management of poisoning. Surgical interventions including tarsorrhaphy, amniotic membrane transplantation, stem cell transplantation and corneal transplantation could reduce the harm to the victims.

Abstract 5-Fluorouracil (5-FU) is one of the most common chemotherapeutic agents used in treating solid tumors, and the 5-FU-induced cardiotoxicity is the second cause of cardiotoxicity induced by chemotherapeutic drugs. Propolis (Pro) has vigorous anti-inflammatory activity. Its cardio-protective characteristic against doxorubicin-induced cardiotoxicity was previously proven. The current study aimed to appraise the effect of Pro on 5-FU-induced cardiotoxicity in rats. Twenty-four male Wistar rats were divided into four groups: Control, 5-FU, 5-FU + Pro 250 mg/kg, and 5-FU + Colchicine (CLC) 5 mg/kg. Different hematological, serological, biochemical, histopathological, and molecular assays were performed to assess the study’s aim. Moreover, a rat myocardium (H9C2(2–1)) cell line was also used to assess this protective effect in-vitro. 5-FU resulted in significant cardiotoxicity represented by an increase in malondialdehyde (MDA) levels, cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) expression, cardiac enzyme levels, and histopathological degenerations. 5-FU treatment also decreased bodyweight, total anti-oxidant capacity (TAC), catalase (CAT) levels, blood cell counts, and hemoglobin (Hb) levels. In addition, 5-FU disrupted ECG parameters, including increased elevation in the ST-segment and increased QRS complex and QTc duration. Treating with Pro reduced oxidative stress, cardiac enzymes, histopathological degenerations, and COX-2 expression in cardiac tissue alleviated ECG disturbances and increased the number of blood cells and TAC levels. Moreover, 5-FU-induced bodyweight loss was ameliorated after treatment with Pro. Our results demonstrated that treatment with Pro significantly improved cardiotoxicity induced by 5-FU in rats.

Background: This study aimed to assess the effect of graphene oxide (GO) nanoparticles mouthwash on oral mucosa, Streptococcus mutans (S. mutans) count in the saliva of rats, and human enamel surface microhardness, in comparison with fluoride mouthwash. Methods: This study was conducted in two phases namely an animal study, and an in vitro experimental study. GO mouthwash (0.005%), sodium fluoride (NaF) mouthwash (0.05%), and a combination of both (0.05% NaF-0.005% GO) were prepared. The oral cavity of 36 rats was inoculated with S. mutans, and they were randomly divided into 4 groups according to the type of mouthwash. The control group received saline mouthwash. Fourteen days after using the mouthwashes, all rats were sacrificed, and the salivary S. mutans count was measured. The buccal and tongue mucosa were also histologically examined for the type and severity of inflammation, number of blood vessels, epithelial thickness, and epithelial keratinization. For microhardness testing, 40 sound extracted human premolars were randomly assigned to four groups (n=10) of culture medium with S. mutans and different mouthwashes. The enamel microhardness was measured at 7 and 14 days, and compared with the baseline value. Results: The mean S. mutans count in the saliva of rats in GO and NaF-GO groups was significantly lower than that in other groups (p

Background: Poisoning is a major public health problem that constitutes a significant share of the global burden of disease. Previous studies conducted in this area indicated the importance of such epidemiological studies. The most critical impact of these studies is their effect on changing current regulations and, therefore, decreasing poisoning cases. We aimed to evaluate all poisoning cases with regard to the patients’ demographics and the involved intoxicants. Methods: The present study was conducted to investigate all poisoning cases who were admitted during a three-year period. Causes of poisoning, hospitalization, management procedures and outcome of the cases were surveyed. A total of 1448 patients referred to Shahid Beheshti Hospital (Babol, Iran) from 2015 to 2018. Results: More than half of the patients were females (51.7%), and the majority of poisoning cases were seen in patients aged between 15 to 25 years (34.2%). It was found that suicide made a large part of poisoning cases (65.6%), and females tend to attempt suicide more than males (64.3% vs. 35.7%, respectively). Also, regular drugs followed by club drugs were the most abundant toxic agents (52.1% and 23.3%, respectively). Aluminum phosphide (AlP) was the most lethal intoxicant in our study, accounting for 68.2% of all deaths. Conclusions: According to the results, it is concluded that the existing regulations for drug control and suicide prevention have not been efficient enough and further actions yet to be made to reduce the consequences of drug- and non-drug-related toxicities.

New Coronavirus which is called 2019-nCoV (2019-Novel-Coronavirus) or SARS-Cov-2 (Severe Acute respiratory Syndrome-Coronavirus 2) causes deadly pneumonia that first appeared in December 2019 in Wuhan city in China. This virus spreads all over the world quickly and made several problems for the community and healthcare system. Several drugs have been tried to manage COVID-19; however, our knowledge of this virus is not complete. At any rate, effective treatment or vaccine for this disease has not been discovered yet. Furthermore, to achieve this goal, more studies are needed on the structure of the virus and its pathogenesis mechanism. In this article, we summarized several articles suggesting treatments of COVID-19.

Background: Nowadays, radiotherapy is used effectively for treatment of head and neck cancers. Mucositis is one of the most important side effects of radiotherapy. Radio-protective agents protect tissues and cells against the adverse effects due to ionizing radiation and cleave radiation-induced free radicals. Lycopene as a potent antioxidant protects cells against oxidative damage by free radical–scavenging. The present study investigated the antioxidant effect of lycopene on oral mucosa of irradiated rats. Methods: In this experimental animal study, 28 rats were placed in four groups as follows: treated with 50 mg /kg of lycopene (L50), solvent+irradiation (SR), 25 mg / kg of lycopene+irradiation (LR25), and 50 mg / kg of lycopene+irradiation (LR50). The rats received lycopene intraperitoneally. On the irradiation day (day 0) and tenth day of radiation, blood samples were taken from the animals for FRAP and TBARS tests. Results: The results showed that the LR50 group didn’t show mucositis higher than Grade 2. There was a significant difference (p

Background: Propolis as a natural product has shown beneficial effects on human health. This study was aimed to investigate the chemical compositions and biological activity of three different extracts of propolis from two distinct geographic areas in Iran. Methods: The chemical composition of Iranian propolis extracts that were collected in the Spring of 2016 from two provinces in northern Iran: Ardabil and Polur in Mazandaran Province were measured through gas chromatography-mass spectrometry (GC-MS) methods. In addition, antimicrobial activity and cytotoxicity effect on HN5 and LNCaP cell lines were evaluated. The data were analyzed using one-way ANOVA and p

In the present study, adsorption behavior of mesoporous molecularly imprinted polymers for bisphenol A was investigated. Molecularly imprinted nanopolymers were synthesized by precipitation polymerization using bisphenol A as a template molecule. Two molecular ratios of templet: functional monomer: cross-linker (1:6:30 (MIP-6) and 1:4:20 (MIP-4)) was considered for experiments. Ethylene Glycol Dimethacrylate (EGDMA) as a Crosslinker, metacrylic acid (MAA) as a functional monomer and 2, 2´-azobisisobutyronitrile (AIBN) as an initiator were used for the synthesis of polymers. In addition, Langmuir and Freundlich adsorption isotherms and pseudo-first-order and pseudo-second-order kinetic models were studied for adsorption mechanism. Results showed that porous polymers with average pore diameter of 13 to 17 nm and specific surface area of 326 to 439 (cm3/g) were obtained. The maximum adsorption capacity was 400.1 μmol/g for MIP-6. SEM analysis showed that the synthesized polymer particles were spherical. The highest adsorption efficiency of bisphenol A achieved by MIP-6 was 71%.

Background: Given that the world's population is aging, the problems associated with osteoporosis and related fractures are increasing. The aim of the study was to evaluate the effect of flaxseed extract on bone mineral density (BMD) in Wistar rats using digital radiography. Methods: In this experimental study, 25 male and 25 female Wistar rats were randomly divided into 5 groups: 1. Control, 2. Calcium and vitamin D (Ca/VitD), 3. 100 mg/kg flaxseed, 4. 200 mg/kg flaxseed, and 5. 400 mg/kg flaxseed. Then, the animals were kept for thirty days. Maxillary and mandibular BMD as well as serum levels of calcium, vitamin D and phosphorus were measured at baseline and after 30 days of keeping the rats. Results: The results showed that serum levels of calcium and phosphorus were not significantly different in all five groups before and after 30 days. Serum levels of vitamin D were significantly higher in the group receiving Ca/vit D (with a mean of 61.6±15.8 in the male group and 85±12.9 in the female group) as compared with other groups (P

Aluminum poisoning has been reported in some parts of the world. It is one of the global health problems that affect many organs. Aluminum is widely used daily by humans and industries. Residues of aluminum compounds can be found in drinking water, food, air, medicine, deodorants, cosmetics, packaging, many appliances and equipment, buildings, transportation industries, and aerospace engineering. Exposure to high levels of aluminum compounds leads to aluminum poisoning. Aluminum poisoning has complex and multidimensional effects, such as disruption or inhibition of enzymes activities, changing protein synthesis, nucleic acid function, and cell membrane permeability, preventing DNA repair, altering the stability of DNA organization, inhibition of the protein phosphatase 2A (PP2A) activity, increasing reactive oxygen species (ROS) production, inducing oxidative stress, decreasing activity of antioxidant enzymes, altering cellular iron homeostasis, and changing NF-kB, p53, and JNK pathway leading to apoptosis. Aluminum poisoning can affect blood content, musculoskeletal system, kidney, liver, and respiratory and nervous system, and the extent of poisoning can be diagnosed by assaying aluminum compounds in blood, urine, hair, nails, and sweat. Chelator agents such as deferoxamine (DFO) are used in the case of aluminum poisoning. Besides, combination therapies are recommended.

Background and Objective. Nonylphenol (NP), as an environmental pollutant, has adverse effects on the reproductive and nervous systems through disrupting the endocrine system and inducing oxidative stress. This study was aimed at investigating the protective effect of melatonin (MLT) on NP-induced reproductive and behavioral disorders in first-generation adult male rats. Methods. Pregnant Wistar rats were randomly assigned into five groups: control, NP (25 mg/kg), NP (25 mg/kg)+MLT (10 mg/kg), NP (25 mg/kg)+MLT (20 mg/kg), and MLT (20 mg/kg). The duration of treatment was 21 days from gestation time. Morris water maze was used to assess learning and memory. NP concentrations of serum and testicular tissue were measured by HPLC. Histological analysis of testicular tissues was done by H&E staining. Results. Behavioral study showed that NP does not impair learning and memory in first-generation rats. Histomorphometric results showed that NP can significantly reduce the cross-sectional area of the seminiferous tubules and the epithelium, the diameter and number of seminiferous tubules, the thickness of the epithelium, and the number of spermatocytes and spermatogonia compared to other groups. MLT reversed the NP-induced histomorphometric. Also, it changes and increased the activity of superoxide dismutase (SOD), total antioxidant capacity (TAC), and catalase (CAT). The level of malondialdehyde (MDA) significantly decreased in MLT-treated groups compared with the NP group. Conclusion. Our finding showed that MLT enhanced the learning process and reduced NP-induced testicular tissue damage through its antioxidants and cytoprotective effects.

Background. This study aimed to evaluate the impact of ketorolac on the pharmacokinetics of 5-FU and its effect on the efficacy of 5-fluorouracil (5-FU) on the HT-29 cell line. Methods. Cell culture: the HT-29 cell line was treated with different concentrations of 5-FU, ketorolac, and combination of 5-FU and ketorolac for 24 and 48 hours. The cell viability (%) was calculated by the MTT assay. Animal study: rats were randomly divided into control and pretreatment groups. The control group received physiological saline, whereas the pretreatment group received ketorolac by intraperitoneal (i.p.) injections on a daily basis for 14 days. On the 15th day, both groups received 5-FU (i.p.). Blood samples were collected at different times for HPLC analysis, and 5-FU pharmacokinetic parameters were calculated. Results. At cell culture study, in a certain concentration range, combination therapy showed synergistic effects (

AimsAcute myeloblastic leukemia (AML) is the most common type of acute leukemia in adults. Despite numerous treatment strategies including chemotherapy and radiotherapy, a large number of patients do not respond to treatment and experience relapse. The main problem of these patients is the development of resistance to anti-cancer drugs. Therefore, any endeavor to reduce drug resistance in these patients is of high priority. In general, several mechanisms such as changes in drug metabolic pathways, drug inactivation, drug target alterations and reduced drug accumulation in the cells contribute to drug resistance of cancer cells. In this context, evidence suggests that exosomes could reduce drug resistance by removing drugs from their parent cells. In the present study, we aimed to investigate the effects of exosome release inhibition on the resistance of U937 cells to PEGylated liposomal doxorubicin (PLD).Main MethodsIn order to find a suitable ABCG2 (ATP-binding cassette sub-family G member 2) transporter substrate, virtual screening was performed among a list of drugs used in leukemia and PLD was selected. U937 cells were treated with PLD with/without co-treatment with the exosome release inhibitor, GW4869. Released exosomes within different study groups were isolated and characterized to determine the differences between groups. Doxorubicin presence in the isolated exosomes was also measured by high performance liquid chromatography (HPLC) to confirm drug export through the exosomes. Finally, the effect of exosome inhibition on the cytotoxicity of PLD on U937 cells was determined using different cytotoxicity assays including the standard lactate dehydrogenase (LDH) release assay and the flow cytometric analysis of apoptotic and non-apoptotic cell death.Key FindingsGW4869 treatment caused a significant decrease in the exosome release of U937 cells compared to the untreated cells, as evidenced by the reduction of the protein content of the isolated exosomes (P

Abstract Background Propolis is a natural bee product with a wide range of biological activities that are related to its chemical composition. The present study investigated the quantification of quercetin (Q) in Ardabil ethanol extract of propolis (AEEP), and then compared its anti-bacterial, anti- biofilm and cytotoxic effects on cancer and normal cell lines. Method In the present study, the chemical composition of AEEP was determined through the high-performance liquid chromatography (HPLC). The AEEP and its main component, quercetin (Q), were evaluated in vitro against 57 oral streptococci by a broth micro-dilution method. The biofilm formation was assessed through the crystal violet staining and MTT assays. The impact of AEEP and Q anti-proliferative effect were evaluated on the fibroblast as normal and cancer cell lines (KB and A431). Results The Q concentration in the composition of AEEP was 6.9% of all its components. The findings indicated that the AEEP and Q were efficient against the cariogenic bacteria and were able to inhibit the S.mutans biofilm adherence at a sub-MIC concentration. Moreover, electron micrographs indicated the inhibition of biofilms compared to control biofilms. In addition, the AEEP and Q indicated a dose-dependent cytotoxic effect on A431 and KB cell lines. On the contrary, they had no cytotoxic effect on fibroblast cells. Conclusion The results indicated that the synergistic impact of main components of AEEP was related to the inhibition of the cancer cell proliferation, cariogenic bacteria and oral biofilm formation. It may play a promising role in the complementary medicine and, it is suggested to be used as food additives.

Background: Orofacial pain is a form of inflammatory pain usually treated with corticosteroids, which have many side effects. Objective: The aim of this study was to investigate the clinical and histological profile of antinociceptive effects of hydroalcoholic extract of caper (Capparis spinosa) for the first time in the orofacial region. Methods: This experimental study was carried out at Babol University of Medical Sciences in 2018. Thirty-six male Wistar mice were divided into 6 groups: The first group received saline, the second group received dexamethazone, and four groups received different doses (10, 20, 50, 100 mg/kg) of caper extract. In the formalin test, 1% formalin solution was injected into the right submucosal layer of the lip and lateral area of the nose. Pain intensities were recorded at 5-min blocks for 60 min after injection. Dose effect of caper on pain was recorded. The mice were euthanized and the oral area was biopsied and stained with Hematoxylin-eosin, Toluidine blue, and Congo red. Data were analyzed using repeated measures ANOVA and t-test by IBM-SPSS version 20. Results: Caper produced antinociceptive effects in comparison with saline groups (p0.999). Histopathologic examination revealed the highest thickness of epithelium, fibrous, and muscular tissue density and the lowest inflammatory infiltration at the dose of 100 mg/kg of caper. Conclusion: The results of the present study suggest that hydroalcoholic extract of caper possesses antinociceptive activity in a dose-dependent manner and caper-induced antinociception might be mediated, at least in part, by anti-inflammatory effects.

Among the blistering (vesicant) chemical warfare agents (CWA), sulfur mustard is the most important since it is known as the “King of chemical warfare agents”. The use of sulfur mustard has caused serious damages in several organs, especially the eyes, skin, respiratory, central and peripheral nervous systems after short and long term exposure, incapacitating and even killing people and troops. In this review, chemical properties, mechanism of actions and their effects on each organ, clinical manifestations, diagnostic evaluation of the actions triage, and treatment of injuries have been described.

Background. The ultimate aim of periodontal treatment is to regenerate periodontium and regenerative treatment after that. The aim of this study was to evaluate the effect of PRGF with 1% metformin biofilm in the treatment of two-wall intrabony periodontal defects. Methods. In this clinical trial, 8 patients with moderate chronic periodontitis and two-wall intrabony defect were selected. The defects were assigned to 4 groups: debridement, 1% metformin, PRGF, PRGF and metformin. The parameters of vertical probing depth, vertical clinical attachment level and gingival index were measured at baseline, immediately before surgery, and 3 and 6 months after surgery. In addition, the radiographic changes were evaluated with digital subtraction radiography before and 6 months after surgery. Analysis of the results was performed with repeated measurements, Friedman test and chisquared test. Results. All the groups exhibited improvements in all the clinical parameters after 6 months. Inter-group comparison of GI, CAL and PPD parameters revealed no statistically significant differences. Radiographic changes in the group of 1% metformin with PRGF revealed statistically significant differences compared with other groups; however, there were no statistically significant differences in other groups. Conclusion. Application of PRGF with 1% metformin in intrabony two-wall periodontal defects was effective in improving the clinical parameters but this effect revealed no difference compared with other groups; however, in terms of radiographic changes significant improvements were noted

Background: Enteric-coated capsules are solid dosage forms which are designed to bypass the stomach and release the drug in the small intestine. This study was done to compare pharmacokinetics of ibuprofen tablet and ibuprofen as enteric-coated capsule using sodium alginate beads. Methods: A crossover randomized study was performed on 12 healthy volunteers receiving a single dose of regular ibuprofen tablet (200 mg) and enteric-coated capsule (200 mg). The washout time between the periods was one month. Pharmacokinetic and pharmacodynamic blood samples were collected for 16 hours following treatment. High-performance liquid chromatography (HPLC) method used the following specifications: C18 column with 4.6 mm diameter & 25 mm length, the fluorescent detector of excitation and emission wavelengths were 224 and 290 nm, respectively. Results: After a single oral dose of ibuprofen formulations, the median times to maximum concentration were 60 and 240 minutes in ibuprofen tablet (200 mg) and enteric-coated capsule, respectively. The maximum levels for the participants receiving ibuprofen tablet and enteric-coated capsule were 11.71±1.3 and 10.32±4.19 µg/mL, respectively. The pharmacokinetic (PK) modeling data showed the area under curve (AUC) to be 61.51 hours & 86.62 hours for the group receiving the tablet and the capsule, respectively. Conclusion: According to the results, in is concluded that enteric coating may delay the onset of ibuprofen effect and increases the duration of action. This formulation has advantages over the conventional drug delivery systems as it lengthens the dosing intervals and also increases patient compliance for chronic pain.

Background and Aim: Because of complexity in root canals, irrigating solutions are needed in addition to mechanical instrumentation for thorough cleansing of the root canal system. This in-vitro study was designed to determine the inhibitory effect of arginine, protamine, and aqueous extracts of green tea and aloe vera against Enterococcus faecalis (E. faecalis), which causes endodontic failure. Materials and Methods: In this experimental study, aqueous extracts of green tea and aloe vera and protamine at a concentration of 400 mg/ml and arginine at a concentra-tion of 160 mg/ml were used. E. faecalis was cultured on Mueller-Hinton broth, and minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the test materials against these microorganisms were determined using serial dilutions and according to the microdilution test. The positive control was 2.5% sodium hypochlorite (NaOCl). Results: Aqueous extract of aloe vera has high antibacterial activity against E. faecalis (MIC=12.5 mg/ml and MBC=100 mg/ml), and protamine had the least effect (MIC=400 mg/ml and MBC>400 mg/ml) compared to other test materials. NaOCl, with MIC and MBC of 0.25 mg/ml against E. faecalis, showed higher antibacterial activity compared to other test materials. Conclusion: Among the tested materials, except for NaOCl as a positive control, aqueous extract of aloe vera showed better antibacterial properties against E. faecalis.

Objectives: This study investigated the efficacy of theobromine in comparison with 0.05% sodium fluoride solution for remineralization of initial enamel caries lesions (IECLs). Materials and Methods: Ninety non-carious extracted premolars were sectioned longitudinally into buccal and lingual segments. Caries-like lesions were induced in each segment using acidified gel. Forty-five buccal segments were used for surface microhardness (SMH) test, and 45 buccal segments were used for energy-dispersive X-ray spectroscopy (EDS). The lingual segments were used as the control group for EDS and SMH test. The baseline SMH was measured with a Vickers hardness tester, and the baseline calcium content was analyzed by EDS. Each test group was divided into three subgroups for treatment with (1) artificial saliva, (2) 1.1 mol/L theobromine, and (3) 0.05% sodium fluoride. Remineralization and demineralization were done by daily pH cycling to simulate the oral environment. Samples in each group were immersed in treatment solutions for 1 min before and after the remineralizing cycle. After a 7-day cycle, the SMH test and EDS analysis were performed again. Data were analyzed using one-way ANOVA, Tukey’s post-hoc test, and paired sample t-test (P

Background. Hydroxychloroquine with or without azithromycin was one of the common therapies at the beginning of the COVID-19 pandemic. They can prolong QT interval, cause torsade de pointes, and lead to sudden cardiac death. We aimed to assess QT interval prolongation and its risk factors in patients who received hydroxychloroquine with or without azithromycin. Methods. This study was a retrospective cohort study. One hundred seventy-two confirmed COVID-19 patients were included in this study, hospitalized at Babol University of Medical Sciences hospitals between March 5, 2020, and April 3, 2020. Patients were divided into two groups: hydroxychloroquine alone and hydroxychloroquine with azithromycin. Electrocardiograms were used for outcome assessment. Results. 83.1% of patients received hydroxychloroquine plus azithromycin vs. 16.9% of patients who received only hydroxychloroquine. The mean age of patients was 59.2±15.4.The mean of posttreatment QTc interval in the monotherapy group was shorter than the mean of posttreatment QTc interval in the combination therapy group, but it had no significant statistical difference (462.5±43.1 milliseconds vs. 464.3±59.1 milliseconds; p=0.488). Generally, 22.1% of patients had a prolonged QTc interval after treatment. Male gender, or baseline QTc≥450 milliseconds, or high-risk Tisdale score increased the likelihood of prolonged QTc interval. Due to QTc prolongation, fourteen patients did not continue therapy after four days. Conclusions. Hospitalized patients treated by hydroxychloroquine with or without azithromycin had no significant difference in prolongation of QT interval and outcome. The numbers of patients with prolonged QT intervals in this study emphasize careful cardiac monitoring during therapy, especially in high-risk patients.

Objective. Recurrent aphthous stomatitis is one of the most common chronic inflammatory diseases in oral mucosa. Beneficial effects of omega-3 supplements on some inflammatory diseases have been proved. The aim of present study was to evaluate the effect of omega-3 supplements in recurrent aphthous stomatitis management and improve oral health-related quality of life. Methods. In this double-blind clinical trial, 40 patients with minor recurrent aphthous stomatitis were randomly divided into case and control groups. The case group received 1000 mg capsules of omega-3, while the control group received placebo capsules for 6 months. The questionnaires of the ulcer severity score and the chronic oral mucosal disease questionnaire were filled by the patients in three steps, at the baseline session, after 3 months, and after 6 months. The data were analyzed by SPSS 22 software through ANOVA, Mann–Whitney, and chi-square tests. P

Background: Recurrent aphthous stomatitis (RAS) is one of the most common painful oral lesions of which there is no certain treatment. Objective: The aim of this study was to determine the effect of Chitosan mouthwash 0.5% on RAS. Methods: This randomized double-blind crossover clinical trial was conducted at a dental school in Babol, Iran, from 2015 to 2016. Twenty patients with a history of minor aphthous stomatitis were entered into this study. All patients were initially monitored in the first episode without treatment, and then were randomly treated in three other episodes with Chitosan, Triamcinolone or Biogel mouthwashes. The ulcer size and pain intensity by using visual analogous score (VAS) were recorded in each episode. Data were analyzed by ANOVA and Tukey test. We used SPSS version 20 to analyze data. Results: The mean ulcer size on the fifth day (p=0.026, p=0.042, respectively) and VAS on the third and fifth days (p=0.011, p=0.013, respectively) were significantly less in Triamcinolone and Chitosan groups than Biogel and the no treatment episode. There were no significant differences between Chitosan and Triamcinolone groups in the average ulcer size and pain intensity in all the examination days. Conclusions: Chitosan mouthwash is effective on pain relief and reducing ulcer size of minor aphthous stomatitis and this effect is almost the same as Triamcinolone mouthwash. Clinical trial registration: The study was registered and approved by Iranian Registry of Clinical Trials (http://www.irct.ir) with IRCT ID: IRCT2015030718753N2. Funding: The study was funded by Deputy of Research and Technology of Babol University of Medical Sciences (ref. no.: 9133625).

Background and purpose: The antioxidant property of lycopene is well proven. The aim of this study was to evaluate the effect of lycopene on Oral Mucositis (OM) in rat induced by gamma radiation. Materials and methods: This experimental study was conducted in 28 male Wistar rats. They were divided into four groups (n=7 per group). 15 Gy of gamma radiation was used for 7 min and 39 sec. The rats were intraperitoneally (IP) injected within 6 days (daily) and their lips and tongues were examined to assess the incidence and severity of mucositis. Blood samples were also taken from the mice on days zero and six and the serum total antioxidant was evaluated by biochemical assays. Data analysis was done in SPSS V18. One-way ANOVA was done to analyze the datasets for mucositis and serum antioxidant capacity. Mann–Whitney test was applied for pairwise comparison of therapeutic groups in terms of the severity of mucositis. Results: Lycopene caused no delay in the onset of mucositis but the severity of mucositis was lower in lycopene groups compared to that in the placebo group. According to FRAP test, total antioxidant capacity changes of serum were significant between treatment groups on day six between L50 and PR, L50 and LR25, PR and LR50, and LR25 and LR50 groups. Conclusion: Lycopene did not delay the onset of mucositis in treatment groups, but the severity of mucositis was lower in lycopene groups compared with that in placebo group.

Cadmium poisoning has been reported from many parts of the world. It is one of the global health problems that affect many organs and in some cases it can cause deaths annually. Long-term exposure to cadmium through air, water, soil, and food leads to cancer and organ system toxicity such as skeletal, urinary, reproductive, cardiovascular, central and peripheral nervous, and respiratory systems. Cadmium levels can be measured in the blood, urine, hair, nail and saliva samples. Patients with cadmium toxicity need gastrointestinal tract irrigation, supportive care, and chemical decontamination traditional-based chelation therapy with appropriate new chelating agents and nanoparticle-based antidotes. Furthermore it has been likewise recommended to determine the level of food contamination and suspicious areas, consider public education and awareness programs for the exposed people to prevent cadmium poisoning.

Background: Azithromycin (AZM) is used in periodontal infections. The present study compared gingival crevicular fluid concentration of azithromycin of two pharmaceutical companies through the HPLC method. Methods: Two groups (n=15) of healthy volunteers participated in this study. The first group received an imported azithromycin (ImAZM) tablet (250 mg, PO) and the second group received an azithromycin tablet (250 mg PO) manufactured by an Iranian pharmaceutical company (IrAZM). Intrasulcular paper points (#30) were used in inter-proximal areas of molars and canines to collect gingival crevicular fluid samples at 6, 12, 36, 84 and 156 hours after drug administration. Results: The maximum concentration of AZM in gingival crevicular fluid was detected in each group 36 hour after administration. The concentration levels for the participants receiving ImAZM and IrAZM were 14.38±5.75 and 12.64±3.53 ng/mL, respectively. The pharmacokinetic (PK) modeling data showed half-life of AZM was 107.47 hr & 91.42 hr while the clearance was 113.02 hr &119.0 hr for the group receiving ImAZM and IrAZM, respectively. No significant differences were observed in other PK parameters, areas under the concentration time curves for the groups were almost identical. Conclusion: According to the results, there were no significant differences between the PK parameters of ImAZM and IrAZM products. It may be concluded that different doses of AZM have relatively similar PK parameters among the healthy participants.

Introduction: Bisphenol A (BPA) and Nonylphenol (NP) have estrogen-like activity, and some of their adverse biological effects have been demonstrated. This study was designed to determine the association of plasma and tissue concentrations of BPA and NP and changes in the parameters of the reproductive system in rats. Methods: Male Wistar rats were administered three doses of BPA and NP (5, 25, and 125 µg/kg) by gavage for 35 consecutive days in 2014-2015, and a 2-ml blood sample was taken from each treated rat. Concentrations of BPA and NP in the blood were determined using the HPLC-fluorescence detection method. The sperm are produced in the epididymis and vas deferens, and they swim up in Ham`s F10 solution, and, then, various parameters were evaluated using an invert microscope, and they included the count, motility, and morphology of the sperm. Results: The weight of the testes and prostate in the rats receiving BPA and NP treatment showed significant decreases compared to the control group. Similarly, NP created higher concentration than BPA in the serum (e.g., 5.48 ± 0.65 vs. 1.36 ± 0.25, at 125 µg/kg). Compared to the control group, dose-dependent significant decreases in count and motility in the sperm were observed following the administration of BPA (25 and 125 µg/kg) and NP (all three doses). Morphologic aspects of the rats` sperm were changed in various doses of BPA and NP Conclusions: According to our findings, BPA and NP induced dose-dependent toxic effects on various parameters, i.e., sperm toxicity, weight of the testes, and weight of the prostate gland.

Background: Treatment of chronic constipation is creating one of the major problems for doctors and patients. Pyridostigmine increases the gastrointestinal motility through the effects on cholinesterase. It seems that this mechanism can reduce chronic constipation. The aim of this study was to compare the effects of pyridostigmine and bisacodyl on chronic constipation. Methods: This study was conducted on 68 patients who suffered from chronic constipation. Patients were randomly divided into two groups of Pyridostigmine and bisacodyl in which each consisted of 34 patients, respectively. Bristol stool form score, straining defecation, the time of defecation, the number of defecation per week, sense of incomplete evacuation and self-digitation were collected by means of questionnaires and the data were compared. Results: Sixty-eight patients with the mean age of 68.12±84.49 were studied. The mean difference in the frequency of defecation per week, VAS score, the time to defecation and the Bristol Stool form Scale in pre and post-treatment were 4.33±1.88, 5.96±2.29, 12.30±7.95 min and 2.10±0.95 in pyridostigmine group and 2.96±1.81, 4.06±2.22, 6.67±5.23 min and 1.41±0.84 in bisacodyl group, respectively. The significant difference was observed in both pyridostigmine and bisacodyl groups (P=0.005, P=0.002, P=0.002 and P=0.005, respectively). 60% and 32.3 of patients in pyridostigmine and bisacodyl groups recovered from self-digitations, respectively. In pyridostigmine and bisacodyl groups, 66.7% and 32.3 of them had improvement in the sense of incomplete defecation, respectively. Conclusion: Pyridostigmine and bisacodyl significantly improved the symptoms of chronic constipation similarly.

Background: Insect vector control is facing the challenges of resistance development and environmental hazards caused by synthetic pesticides. This has led to a considerable market opportunity for botanical insecticides. In this scenario, our study investigated the potential of selected bioactive monoterpenoids, carvacrol and thymol, as safe and effective tools to control the West Nile vector Culex pipiens. Furthermore, the combined effect of thymol-carvacrol mixtures and their possible interactions were assessed. Methods: For determining larvicidal and ovicidal 50% lethal concentration (LC50), each monoterpenoid was tested at different concentrations (5–500 mg/L). Then, the fixed ratio method was used for evaluating their combinational efficacy. Results: Carvacrol was more toxic against larvae of Cx. pipiens, with a LC50 value of 14 mg/L, whereas thymol exhibited a LC50 value of 49 mg/L. Comparable trends of efficacy were observed when toxicity on Cx. pipiens eggs was investigated, with LC50 values of 7 and 13 mg/L for carvacrol and thymol, respectively. In combinational toxicity assays, the mixture thymol-carvacrol at 1:4 ratio achieved a synergistic effect against larvae of Cx. pipiens, whereas an additive effect was observed on eggs. Other ratios showed antagonistic effects. Conclusions: Overall, our findings pointed out that the 1:4 ratio of thymol-carvacrol blend can enhance the insecticidal efficacy on Cx. pipiens young instars and can be considered further as active ingredient for developing botanical insecticides to be used in mosquito control operations.