Rheum khorasanicum. Hydroalcoholic root extract induces cell death in human colorectal adenocarcinoma: An in vitro and in silico study.

Colorectal cancer (CRC) is the second greatest cause of cancer-related death in the world and chemotherapy, as an important part of CRC treatment, has some drawbacks, including systemic toxicity. Therefore, it is crucial to discover new and more effective CRC treatment plans. Rheum khorasanicum (R. khorasanicum) is a medicinal plant with high flavonoids, stilbenes, and anthraquinone contents, so it can be a potential source of antioxidants and can be used for therapeutic purposes and trigger apoptosis in cancer cells. In this study, we investigated the effects of hydroalcoholic root extract of R. khorasanicum treatment on inducing mitochondrial apoptosis of HT-29 and Caco-2 human colorectal adenocarcinoma cells. Firstly, the total phenolic and flavonoid content was determined. Then, the cytotoxic effects of R. khorasanicum on cells of three different types, including HT-29 and Caco-2 colon cancer cells as well as normal 3T3 cells were assessed using the MTT assay. To investigate the characteristics of cellular death, flow cytometry, and western blotting were performed. The results of this study indicated considerable phenolic (356.4±9.4 GAE/gDW) and flavonoid (934.55±17.1 QE/gDW) contents in R. khorasanicum. MTT assay's finding indicated that 100, 60, and 30µg/mL concentrations of R. khorasanicum reduce cell viability in HT-29 and Caco-2 cell lines significantly (P<0.05). It has been also revealed that R. khorasanicum extract induces apoptosis rather than necrosis in these cell lines. Moreover, Bcl-2 expression was significantly reduced in both HT-29 and Caco-2 cell lines, while Bax and cleaved caspase-3 expression soared considerably in the groups under R. khorasanicum treatment (P<0.05). In conclusion, our findings have suggested that high phenol and flavonoid contents of R. khorasanicum root extract possibly play an important role in cell cytotoxicity and apoptosis induction in HT-29 and Caco-2 colon cancer cells.

Impact of a 50bp insertion/deletion polymorphism of the superoxide dismutase-1 on oxidative stress status and risk of keratoconus.

Keratoconus (KC) is characterized by the predominant primary ectatic disease, affecting the cornea, necessitating corneal transplants in some cases. While some loci associated with KC risk have been identified, the understanding of the disease remains limited. Superoxide dismutase (SOD) enzymes play a crucial role in countering the reactive oxygen species and providing protection against oxidative stress (OS). Accordingly, the objective of this study was to investigate a potential association of a 50 nucleotide base pairs (bp) insertion/deletion (I/D) within the SOD1 promoter, and the located 1684 bp upstream of the SOD1 ATG, with KC in the Iranian population. Additionally, an assessment was conducted on SOD activity and the total antioxidant capacity (TAC), as determined by the ferric reducing-antioxidant power assay, along with malondialdehyde (MDA) levels. In this case-control study, genomic DNA was extracted from the blood cells of KC (n = 402) and healthy (n = 331) individuals. The genotype of this gene was determined using the PCR technique. Furthermore, the amount of SOD enzyme activity and the MDA and TAC levels were measured in the serum of the study groups. The (I/I) genotype was present in 84.23%, the (I/D) genotype in 15.06%, and the (D/D) genotype in 0.69% of both groups. A statistically significant relationship was seen between different genotypes and TAC, MDA, and SOD1 activity indices (P < 0.05). Individuals with the D/D genotype exhibited a decrease in total antioxidant capacity, an increase in the amount of MDA, and a decrease in SOD1 enzyme activity (P < 0.05). Moreover, the logistic regression analysis of KC development indicated that elevated levels of MDA increased the risk of KC incidence in the patient group compared to the healthy group, while a higher activity of SOD1 and greater values of TAC decreased the KC risk. The removal of the 50 bp fragment reduced SOD1 activity and elevated OS levels, thereby impacting the oxidant-antioxidant balance. This could potentially play a significant role in individuals afflicted by KC.

Preparation and Evaluation of Preventive Effects of Inhalational and Intraperitoneal Injection of Myrtenol Loaded Nano-Niosomes on Lung Ischemia-Reperfusion Injury in Rats.

INTRODUCTION: Ischemia-reperfusion injury (IRI) is directly related to forming reactive oxygen species, endothelial cell injury, increased vascular permeability, and the activation of neutrophils and cytokines. Niosomes are nanocarriers and an essential part of drug delivery systems. We aimed to investigate the effects of myrtenol's inhaled and intraperitoneal niosomal form, compared to its simple form, on lung ischemia reperfusion injury (LIRI). MATERIAL AND METHOD: Wistar rats were divided into ten groups. Simple and niosomal forms of myrtenol were inhaled or intraperitoneally injected daily for one week prior to LIRI. We evaluated oxidative stress, apoptotic, and inflammatory indices, nitric oxide, inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS) and histopathological indices. RESULTS: Pretreatment with simple and niosomal forms of myrtenol significantly inhibited the indices of pulmonary edema, pro-inflammatory cytokines and proteins, oxidant agents, nitric oxide, iNOS, apoptotic proteins, congestion of capillaries, neutrophil infiltration, and bleeding in the alveoli. Furthermore, myrtenol increased anti-inflammatory cytokines, anti-oxidants agents, eNOS, anti-apoptotic proteins and the survival time of animals. The niosomal form of myrtenol showed a more ameliorative effect than its simple form. CONCLUSION: The results showed the superior protective effect of the inhalation of myrtenol niosomal form against LIRI compared to its simple form and systemic use.

Inhalation of Spray-Dried Extract of Salvia rosmarinus Spenn Alleviates Lung Inflammatory, Oxidative, and Remodeling Changes in Asthmatic Rats.

INTRODUCTION: For centuries, Salvia rosmarinus Spenn has been applied as folk medicine to cure different diseases due to its anti-inflammatory, antibacterial, antioxidant, antifungal, and antitumor effects. To find bioactive medicinal herbs exerting a protective effect on airway inflammation and remodeling, we assessed the anti-oxidative and anti-inflammatory effects of an aqueous spray-dried extract of Salvia rosmarinus Spenn. (rosemary) in an ovalbumin-induced asthmatic rat model. METHODS: Rats were randomly divided into normal control (control), asthma, asthma+rosemary extract (RE) (13 mg/kg), asthma+RE (50 mg/kg), and asthma+budesonide groups. After 50 days, animals were anesthetized, and then blood, bronchoalveolar lavage fluid (BALF), and lung tissues were collected for subsequent serological and pathological studies. Histopathology of lung tissues was evaluated by H&E staining. The oxidative stress parameters and airway inflammation factors in BALF and lung tissue were explored. RESULTS: Using thin layer chromatography, the presence of rosmarinic acid was confirmed in aqueous extract of rosemary. Furthermore, RE markedly decreased immunoglobulin E levels (50 mg/kg; p < 0.001 vs. asthma group) and inflammatory cytokines (50 mg/kg; p < 0.001 vs. asthma group) and increased antioxidant enzymes (50 mg/kg, p < 0.001 vs. asthma group). Furthermore, RE at a concentration of 50 mg/kg obviously reduced the number of inflammatory cells, goblet cells, and pathological changes compared to the asthma group. CONCLUSION: The results showed that RE administration might prevent or alleviate allergic asthma-related pathological change, probably via antioxidant and anti-inflammatory mechanisms.

Structure-Based Drug Design for Targeting IRE1: An in Silico Approach for Treatment of Cancer.

BACKGROUND: Endoplasmic Reticulum (ER) stress and Unfolded Protein Response (UPR) play a key role in cancer progression. The aggregation of incorrectly folded proteins in the ER generates ER stress, which in turn activates the UPR as an adaptive mechanism to fix ER proteostasis. Inositol-requiring enzyme 1 (IRE1) is the most evolutionary conserved ER stress sensor, which plays a pro-tumoral role in various cancers. Targeting its' active sites is one of the most practical approaches for the treatment of cancers. OBJECTIVE: In this study, we aimed to use the structure of 4µ8C as a template to produce newly designed compounds as IRE1 inhibitors. METHODS: Various functional groups were added to the 4µ8C, and their binding affinity to the target sites was assessed by conducting a covalent molecular docking study. The potential of the designed compound for further in vitro and in vivo studies was evaluated using ADMET analysis. RESULTS: Based on the obtained results, the addition of hydroxyl groups to 4µ8C enhanced the binding affinity of the designed compound to the target efficiently. Compound 17, which was constructed by the addition of one hydroxyl group to the structure of 4µ8C, can construct a strong covalent bond with Lys907. The outcomes of ADMET analysis indicated that compound 17 could be considered a drug-like molecule. CONCLUSION: Our results revealed that designed compound 17 could inhibit IRE1 activity. Therefore, this designed compound is a remarkable inhibitor of IRE1 and introduces a promising therapeutic strategy for cancer treatment.

Lithium and zinc levels along with oxidative status in myocardial infarction: A case-control study.

Background: Coronary artery disease (CAD) and myocardial infarction (MI) are the most prevalent diseases globally. While several risk factors for MI are well assessed, the influence of trace elements on MI has not been thoroughly studied. This study aimed to evaluate lithium (Li) and zinc (Zn) levels in MI patients and healthy control and assess their relationship with oxidative stress (OS) parameters, such as nitric oxide (NO) and total antioxidant capacity (TAC). Methods: This case-control study was performed on 182 patients with MI and 83 healthy subjects at Shafa Hospital in Kerman, Iran. MI patients were divided into two groups based on the angiography results: those with coronary artery block above 50 % (CAB >50 %, n = 92) and those with coronary artery block below 50 % (CAB <50 %, n = 90). A flame atomic absorption spectrometer was used to detect Li and Zn levels, and biochemical indices were measured by an autoanalyzer. Also, ferric reducing antioxidant power assay and the Griess method were used to measure the amounts of NO and TAC. Results: The levels of TAC and Li were significantly higher in the control group than in the patient groups (in both CAB >50 % and CAB <50 % groups). Furthermore, in the CAB <50 % group, TAC and Li levels were significantly higher than in the CAB >50 % group. In the Zn levels evaluation, higher concentration was seen in the CAB >50 % group compared to the CAB <50 % group (P < 0.05). Moreover, Zn and NO levels were significantly higher in both CAB groups compared to controls. In continue, Li levels had a positive association with TAC and ejection fraction percentage (EF%) as well as a negative association with NO levels and Zn levels had a significant positive association with NO and a negative association with TAC. In logistic regression analysis, Li, TAC, and high-density lipoprotein-cholesterol significantly decreased the odds ratio (OR) of MI, whereas Zn, NO, total cholesterol, triglyceride, low-density lipoprotein-cholesterol, and high-sensitivity C-reactive protein (hs-CRP) significantly increased the OR of MI. Furthermore, the area under the curve (AUC) analysis indicated that Li had the highest AUC for the diagnosis of CAB >50 % (Li < 167 ng/mL), and Zn ≥ 1810 µg/mL increased disease severity. Conclusion: Our investigation revealed that Li had a protective effect against CAD by decreasing OS and increasing EF%. However, Zn at concentrations higher than 1810 µg/mL was found to be cytotoxic and increased the risk of MI through increased OS. Taken togather, it could be concluded that Li supplementation may decrease the risk of CAD.

Antiviral and antimicrobial applications of chalcones and their derivatives: From nature to greener synthesis.

Chalcones and their derivatives have been widely studied due to their versatile pharmacological and biological activities, such as anti-inflammatory, antibacterial, antiviral, and antitumor effects. These compounds have shown suitable antiviral effects through the selective targeting of a variety of viral enzymes, including lactate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), fumarate reductase, protein tyrosine phosphatase, topoisomerase-II, protein kinases, integrase/protease, and lactate/isocitrate dehydrogenase, among others. Chalcones and their derivatives have displayed excellent potential for combating pathogenic bacteria and fungi (especially, multidrug-resistant bacteria). However, relevant mechanisms should be further explored, focusing on inhibitory effects against DNA gyrase B, UDP-N-acetylglucosamine enolpyruvyl transferase (MurA), and efflux pumps (e.g., NorA), among others. In addition, the antifungal and antiparasitic activities of these compounds (e.g., antitrypanosomal and antileishmanial properties) have prompted additional explorations. Nonetheless, systematic analysis of the relevant mechanisms, biosafety issues, and pharmacological properties, as well as clinical translation studies, are vital for practical applications. Herein, recent advancements pertaining to the antibacterial, antiviral, antiparasitic, and antifungal activities of chalcones and their derivatives are deliberated, focusing on the relevant mechanisms of action, crucial challenges, and future prospects. Furthermore, due to the great importance of greener and more sustainable synthesis of these valuable compounds, especially on an industrial scale, the progress made in this field has been briefly discussed. Hopefully, this review can serve as a catalyst for researchers to delve deeper into the exploration and designing of novel chalcone compounds with medicinal properties, especially against pathogenic viruses and multidrug-resistant bacteria as major causes of concern for human health.

Boosting therapeutic efficacy of mesenchymal stem cells in pulmonary fibrosis: The role of genetic modification and preconditioning strategies.

Pulmonary fibrosis (PF) is the end stage of severe lung diseases, in which the lung parenchyma is replaced by fibrous scar tissue. The result is a remarkable reduction in pulmonary compliance, which may lead to respiratory failure and even death. Idiopathic pulmonary fibrosis (IPF) is the most prevalent form of PF, with no reasonable etiology. However, some factors are believed to be behind the etiology of PF, including prolonged administration of several medications (e.g., bleomycin and amiodarone), environmental contaminant exposure (e.g., gases, asbestos, and silica), and certain systemic diseases (e.g., systemic lupus erythematosus). Despite significant developments in the diagnostic approach to PF in the last few years, efforts to find more effective treatments remain challenging. With their immunomodulatory, anti-inflammatory, and anti-fibrotic properties, stem cells may provide a promising approach for treating a broad spectrum of fibrotic conditions. However, they may lose their biological functions after long-term in vitro culture or exposure to harsh in vivo situations. To overcome these limitations, numerous modification techniques, such as genetic modification, preconditioning, and optimization of cultivation methods for stem cell therapy, have been adopted. Herein, we summarize the previous investigations that have been designed to assess the effects of stem cell preconditioning or genetic modification on the regenerative capacity of stem cells in PF.

Effect of trehalose on miR-132 and SIRT1 in the hippocampus of aged rats.

Aging causes substantial molecular to morphological changes in the brain. The brain cells are more susceptible towards oxidative damage due to impaired antioxidant defense system. Sirtuin1 (SIRT1) is a crucial cellular survival protein, which its gene has been identified as a direct target of microRNA 132 (miR-132). Trehalose contributes to preventing neuronal damage through several mechanisms. However, little is known about the interactive effects of aging and trehalose on the expression pattern of miR-132 and SIRT1 in the hippocampus. Male Wistar rats were divided into four groups. Two groups of aged (24 months) and young (4 months) rats were administered 2% trehalose solution for 30 days. Two other groups of aged and young rats received regular tap water. At the end of treatment, the levels of Sirt1 mRNA and its protein, malondialdehyde, protein carbonyl content, total antioxidant capacity, tumor necrosis factor α (TNF-α), as well as the expression of miR-132 were measured in the hippocampus. We found that trehalose treatment upregulated the expression of SIRT1 and miR-132. Moreover, administration of trehalose enhanced the level of total antioxidant activity whereas reduced the levels of lipid peroxidation, protein carbonyl content, and TNF-α. In conclusion, our data indicated that trehalose restored antioxidant status and alleviated inflammation in the hippocampus which was probably associated with the upregulation of SIRT1 and miR-132.

Graphene- and MXene-based materials for neuroscience: diagnostic and therapeutic applications.

MXenes and graphene are two-dimensional materials that have gained increasing attention in neuroscience, particularly in sensing, theranostics, and biomedical engineering. Various composites of graphene and MXenes with fascinating thermal, optical, magnetic, mechanical, and electrical properties have been introduced to develop advanced nanosystems for diagnostic and therapeutic applications, as exemplified in the case of biosensors for neurotransmitter detection. These biosensors display high sensitivity, selectivity, and stability, making them promising tools for neuroscience research. MXenes have been employed to create high-resolution neural interfaces for neuroelectronic devices, develop neuro-receptor-mediated synapse devices, and stimulate the electrophysiological maturation of neural circuits. On the other hand, graphene/derivatives exhibit therapeutic applicability in neuroscience, as exemplified in the case of graphene oxide for targeted delivery of therapeutic agents to the brain. While MXenes and graphene have potential benefits in neuroscience, there are also challenges/limitations associated with their use, such as toxicity, environmental impacts, and limited understanding of their properties. In addition, large-scale production and commercialization as well as optimization of reaction/synthesis conditions and clinical translation studies are very important aspects. Thus, it is important to consider the use of these materials in neuroscience research and conduct further research to obtain an in-depth understanding of their properties and potential applications. By addressing issues related to biocompatibility, long-term stability, targeted delivery, electrical interfaces, scalability, and cost-effectiveness, MXenes and graphene have the potential to greatly advance the field of neuroscience and pave the way for innovative diagnostic and therapeutic approaches for neurological disorders. Herein, recent advances in therapeutic and diagnostic applications of graphene- and MXene-based materials in neuroscience are discussed, focusing on important challenges and future prospects.

Formulation and Evaluation of the Anti-inflammatory, Anti-oxidative, and Anti-remodelling Effects of the Niosomal Myrtenol on the Lungs of Asthmatic Rats.

Asthma is a common chronic allergic disease that affects a significant percentage of the world's population. Niosomes are nanoparticles consisting of non-ionic surfactants that can be used for drug delivery. This research was designed to investigate the impacts of inhalation of simple and niosomal forms of myrtenol against adverse consequences of asthma in rats. Asthma induction was performed via injection of ovalbumin, followed by its inhalation. Niosomes were created by a heating protocol, and their physicochemical features were evaluated. Forty-nine male Wistar rats were allotted into 7 groups (n=7 each): Control (CTL), vacant niosome (VN), Asthma, Asthma+VN, Asthma+SM (simple myrtenol), Asthma+NM (niosomal myrtenol), and Asthma+B (budesonide). Lung remodeling, serum immunoglobulin E (IgE), inflammatory  and cytokines, and antioxidant factors in the lung tissue and bronchoalveolar fluid (BALF), as well as), were evaluated. The results showed that myrtenol-loaded niosomes had appropriate encapsulation efficiency, kinetic release, size, and zeta potential. The thickness of the epithelial cell layer in the lungs, as well as cell infiltration, fibrosis, IgE, reactive oxygen species, interleukin (IL)-6, and tumor nuclear factor alpha (TNF-α) levels, decreased significantly. In contrast, superoxide dismutase and glutathione peroxide activity increased significantly in the serum and BALF of the treated groups. The niosomal form of myrtenol revealed a higher efficacy than simple myrtenol and was similar to budesonide in ameliorating asthma indices.  Inhalation of simple and niosomal forms of myrtenol improved the detrimental changes in the asthmatic lung. The niosomal form induced more prominent anti-asthmatic effects comparable to those of budesonide.

Nanophotocatalysts in biomedicine: Cancer therapeutic, tissue engineering, biosensing, and drug delivery applications.

Photocatalysis can be considered as a green technology owing to its excellent potential for sustainability and fulfilling several principles of green chemistry. This process uses light radiation as the primary energy source, preventing or reducing the requirement for artificial light sources and exogenous catalytic entities. Photocatalysis has promising applications in biomedicine such as drug delivery, biosensing, tissue engineering, cancer therapeutics, etc. In targeted cancer therapeutics, photocatalysis can be employed in photodynamic therapy to form reactive oxygen species that damage cancerous cells' structure. Nanophotocatalysts can be used in targeted drug delivery, showing potential applications in nuclear-targeted drug delivery along with specific delivery of chemotherapeutics to cancer cells or tumor sites. On the other hand, in tissue engineering, nanophotocatalysts can be employed in designing scaffolds that promote cell growth and tissue regeneration. However, some important challenges pertaining to the performance of photocatalysis, large-scale production of nanophotocatalysts, optimization of reaction/synthesis conditions, long-term biosafety issues, stability, clinical translation, etc. still need further explorations. Herein, the most recent advancements pertaining to the biomedical applications of nanophotocatalysts are reflected, focusing on drug delivery, tissue engineering, biosensing, and cancer therapeutic potentials.

Bacterial Cellulose-Based Materials: A Perspective on Cardiovascular Tissue Engineering Applications.

Today, a wide variety of bio- and nanomaterials have been deployed for cardiovascular tissue engineering (TE), including polymers, metal oxides, graphene/its derivatives, organometallic complexes/composites based on inorganic-organic components, among others. Despite several advantages of these materials with unique mechanical, biological, and electrical properties, some challenges still remain pertaining to their biocompatibility, cytocompatibility, and possible risk factors (e.g., teratogenicity or carcinogenicity), restricting their future clinical applications. Natural polysaccharide- and protein-based (nano)structures with the benefits of biocompatibility, sustainability, biodegradability, and versatility have been exploited in the field of cardiovascular TE focusing on targeted drug delivery, vascular grafts, engineered cardiac muscle, etc. The usage of these natural biomaterials and their residues offers several advantages in terms of environmental aspects such as alleviating emission of greenhouse gases as well as the production of energy as a biomass consumption output. In TE, the development of biodegradable and biocompatible scaffolds with potentially three-dimensional structures, high porosity, and suitable cellular attachment/adhesion still needs to be comprehensively studied. In this context, bacterial cellulose (BC) with high purity, porosity, crystallinity, unique mechanical properties, biocompatibility, high water retention, and excellent elasticity can be considered as promising candidate for cardiovascular TE. However, several challenges/limitations regarding the absence of antimicrobial factors and degradability along with the low yield of production and extensive cultivation times (in large-scale production) still need to be resolved using suitable hybridization/modification strategies and optimization of conditions. The biocompatibility and bioactivity of BC-based materials along with their thermal, mechanical, and chemical stability are crucial aspects in designing TE scaffolds. Herein, cardiovascular TE applications of BC-based materials are deliberated, with a focus on the most recent advancements, important challenges, and future perspectives. Other biomaterials with cardiovascular TE applications and important roles of green nanotechnology in this field of science are covered to better compare and comprehensively review the subject. The application of BC-based materials and the collective roles of such biomaterials in the assembly of sustainable and natural-based scaffolds for cardiovascular TE are discussed.

Carbon dots with tissue engineering and regenerative medicine applications.

Carbon dots (CDs) with unique physicochemical features such as exceptional biocompatibility, low cost, eco-friendliness, abundant functional groups (e.g., amino, hydroxyl, and carboxyl), high stability, and electron mobility have been broadly investigated in nano- and biomedicine. In addition, the controlled architecture, tunable fluorescence emission/excitation, light-emitting potential, high photostability, high water solubility, low cytotoxicity, and biodegradability make these carbon-based nanomaterials suitable for tissue engineering and regenerative medicine (TE-RM) purposes. However, there are still limited pre- and clinical assessments, because of some important challenges such as the scaffold inconsistency and non-biodegradability in addition to the lack of non-invasive methods to monitor tissue regeneration after implantation. In addition, the eco-friendly synthesis of CDs exhibited some important advantages such as environmentally friendly properties, low cost, and simplicity compared to the conventional synthesis techniques. Several CD-based nanosystems have been designed with stable photoluminescence, high-resolution imaging of live cells, excellent biocompatibility, fluorescence properties, and low cytotoxicity, which make them promising candidates for TE-RM purposes. Combining attractive fluorescence properties, CDs have shown great potential for cell culture and other biomedical applications. Herein, recent advancements and new discoveries of CDs in TE-RM are considered, focusing on challenges and future perspectives.

The Association Between Arsenic Levels and Oxidative Stress in Myocardial Infarction: A Case-Control Study.

Cardiovascular diseases (CVDs) are known as the first causes of death throughout the world, and mainly myocardial infarction (MI), lead to 7.4 million deaths annually. Atherosclerosis is the major underlying cause of most CVDs. However, exposure to heavy metals, among other factors, deserves further attention as a risk factor for CVDs. This study was designed to evaluate the levels of arsenic (Ars) in myocardial infarction (MI) patients and healthy individuals as well as assess the association between the incidence of MI and Ars, total antioxidant capacity (TAC), and oxidative stress. This case-control study was conducted among patients with MI (n = 164) and normal individuals (n = 61) at Shafa Hospital in Kerman, Iran. Patients were classified into two groups, including coronary artery blocks above 50% (CAB > 50%, n = 83) and coronary artery blocks less than 50% (CAB < 50%, n = 83) based on their angiography findings. The demographic characteristics, clinical history, biochemical parameters, and serum Ars and TAC levels were evaluated. In the present study, both CAB groups had significantly reduced levels of TAC compared with the control. Furthermore, TAC was lower in the CAB > %50 group compared to the CAB < %50 group. Ars levels were significantly higher in both CAB groups compared with the control. There was a significant positive relationship between CAB and Ars, BG, HbA1c, urea, creatinine, TG, TC, and LDL-c, as well as a negative relationship between HDL-c and TAC. Moreover, TAC levels showed a significant inverse correlation with Ars, HbA1c, and creatinine, and a positive correlation with HDL-c. As risk factors, Ars, hs-CRP, TG, TC, and LDL-c enhance the severity of the disease, and HDL-c and TAC decrease the disease severity. Moreover, ROC curve analysis revealed that the highest AUC for the CAB > %50 (AUC = 78.29), and cytotoxic levels for both CAB groups (Ars ≥ 0.105 ppm), and no significant differences were found between the two groups. Our findings suggest that Ars at ≥ 0.105 ppm is able to increase the risk of MI through the increased OS and decreased TAC.

Opium may affect coronary artery disease by inducing inflammation but not through the expression of CD9, CD36, and CD68.

The molecular mechanisms of opium action with regard to coronary artery disease (CAD) have not yet been determined. The aim of this study was to evaluate the effect of opium on the expression of scavenger receptors including CD36, CD68, and CD9 tetraspanin in monocytes and the plasma levels of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), malondialdehyde (MDA), and nitric oxide metabolites (NOx) in CAD patients with and without opium addiction. This case-control study was conducted on three groups: (1) opium-addicted CAD patients (CAD + OA, n = 30); (2) CAD patients with no opium addiction (CAD, n = 30); and (3) individuals without CAD and opium addiction as the control group (Ctrl, n = 17). The protein and mRNA levels of CD9, CD36, and CD68 were evaluated by the flow cytometry and quantitative polymerase chain reaction (RT-qPCR) methods, respectively. The consumption of atorvastatin, aspirin, and glyceryl trinitrate was found be higher in the CAD groups compared with the control group. The plasma level of TNF-α was significantly higher in the CAD + OA group than in the CAD and Ctrl groups (p = 0.001 and p = 0.005, respectively). MDA levels significantly increased in CAD and CAD + OA patients in comparison with the Ctrl group (p = 0.010 and p = 0.002, respectively). No significant differences were found in CD9, CD36, CD68, IFN-γ, and NOx between the three groups. The findings demonstrated that opium did not have a significant effect on the expression of CD36, CD68, and CD9 at gene and protein levels, but it might be involved in the development of CAD by inducing inflammation through other mechanisms.

Effects of the Ethanol and Ethyl Acetate Extracts of Terminalia chebula Retz. on Proliferation, Migration, and HIF-1α and CXCR-4 Expression in MCF-7 Cells: an In Vitro Study.

Over recent years, much attention has been devoted to the field of screening natural products and/or their novel structures because of reversing cancer progression. The current research work was intended to explore the cytotoxic activity of ethanol and ethyl acetate extracts of dried fruit of Terminalia chebula Retz. (T. chebula) in MCF-7 cell line. High-performance thin-layer chromatographic (HPTLC) method and Folin-Ciocalteu colorimetric techniques were performed. Anti-proliferative activities of T. chebula fruit extracts on the MCF-7 cell line were evaluated using MTT assay. Effects of both extracts on the migration of MCF-7 cells and the size of MCF-7-derived spheroids were also evaluated. Moreover, antioxidant properties were measured by DPPH and FRAP methods. Western blotting was used to measure the HIF-1α and CXCR-4 protein levels. Chebulagic acid, gallic acid, chebulinic acid, and ellagic acid were found as major compounds in both extracts. The total phenolic contents based on gallic acid equivalent (GAE) in the ethanol and ethyl acetate extracts of T. chebula were found to be 453.68 ± 0.31 and 495.12 ± 0.43 mg GAE/g dry weight of the extract, respectively. Both extracts exerted a significant dose- and time-dependent cytotoxicity effect on MCF-7 cells. They also had a marked negative effect on the average size of MCF-7-derived spheroids and their migration rate. None of the extracts exhibited stronger antioxidant activities than vitamin C. Furthermore, both extracts at a concentration of 125 µg/ml could meaningfully decrease the expression levels of HIF-1α and CXCR-4 in MCF-7 cells. These data represent that T. chebula may be a valuable medicinal resource in the regulation of breast cancer proliferation, growth, and metastasis.

Herbal therapy in opioid withdrawal syndrome: A systematic review of randomized clinical trials.

Background: Medicinal plants have revealed much attention as an alternative or complementary treatment for opioid withdrawal syndrome. The current review collects all available literature to verify the efficiency of herbal remedies in the management of symptoms associated with opioid withdrawal. Methods: A systematic literature search was conducted from January 1990 to May 2021 on four bibliographic databases (Scopus, PubMed, Embase, and Web of Science) using the search terms "medicinal plant", "withdrawal syndrome", "opioid", and all their equivalents. All randomized controlled trials (RCTs), published in the English language were included for data synthesis. The search was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA). The Cochrane risk of bias tool was used to verify the quality of the included clinical trials. Findings: A total of 12 RCTs were collected and used for data synthesis. The results of these studies indicated that herbal medicines were effective in treating opioid withdrawal syndrome and could alleviate the withdrawal symptoms, such as abdominal constrictions, diarrhea, bone pain, perspiration, and insomnia, when compared to conventional medications such as buprenorphine, clonidine, and methadone. However, more than 30% of RCTs were found to be at high risk of bias in the areas of selection, performance, detection, attrition, and reporting. Conclusion: Although several RCTs have proven that herbal remedies are effective in reducing opioid withdrawal symptoms, the findings need to be viewed more carefully. Further RCTs with more participants, longer duration, and less risk of bias are needed in the claimed cases.

Effect of an herbal formulation containing Peganum harmala L. and Fraxinus excelsior L. on oxidative stress, memory impairment and withdrawal syndrome induced by morphine.

Background: Traditional Persian medicine has introduced effective remedies in opioid dependence care. One of the most widely used remedies is an herbal formulation containing Peganum harmala L. and Fraxinus excelsior L. (HF). This study investigated the effects of HF to attenuate the withdrawal signs and rewarding effects in morphine-dependent rats.Methods: Forty-nine male Wistar rats were randomly divided into seven groups. The control and vehicle groups received normal saline and sodium carboxymethyl cellulose, respectively. The morphine group received morphine for one week. The single and daily dose of HF groups received morphine similar to the morphine group, and HF (1.4 and 2.8 g/kg) once a day in the daily dose group and only on the last day of the experiment in the single dose of HF group. Finally, the withdrawal signs as well biochemical tests were evaluated. The behavioral parameters were assessed by conditioned place preference (CPP), elevated plus-maze and Y-maze tests. The antioxidant activity of HF was evaluated by measurement of serum contents of malondialdehyde, stable nitric oxide metabolites and total antioxidant capacity (TAC). Moreover, the protein expression of c-fos was assessed by western blotting.Results: Daily treatment with HF significantly reduced the score of CPP behavioral test, all of the withdrawal signs, TAC and the c-fos protein level.Conclusions: The results indicated that HF might be a promising complementary treatment in reducing morphine-induced physical and psychological dependence probably through modulation of c-fos protein expression.