The role of Th17 cells in the pathogenesis and treatment of breast cancer.

Breast cancer is a severe problem worldwide due to an increase in mortality and prevalence among women. Despite early diagnostic procedures as well as advanced therapies, more investigation is required to find new treatment targets. Various factors and mechanisms, such as inflammatory conditions, can play a crucial role in cancer progression. Among them, Th17 cells are identified as effective CD4+ T cells that play an essential role in autoimmune diseases and inflammation which may be associated with anti-tumor responses. In addition, Th17 cells are one of the main factors involved in cancer, especially breast cancer via the inflammatory process. In tumor immunity, the exact mechanism of Th17 cells is not entirely understood and seems to have a dual function in tumor development. Various studies have reported that cytokines secreted by Th17 cells are in close relation to cancer stem cells and tumor microenvironment. Therefore, they play a critical role in the growth, proliferation, and invasion of tumor cells. On the other hand, most studies have reported that T cells suppress the growth of tumor cells by the induction of immune responses. In patients with breast cancer compared to normal individuals, various studies have been reported that the Th17 population dramatically increases in peripheral blood which results in cancer progression. It seems that Th17 cells by creating inflammatory conditions through the secretion of cytokines, including IL-22, IL-17, TNF-α, IL-21, and IL-6, can significantly enhance breast cancer progression. Therefore, to identify the mechanisms and factors involved in the activation and development of Th17 cells, they can provide an essential role in preventing breast cancer progression. In the present review, the role of Th17 cells in breast cancer progression and its therapeutic potential was investigated.

Circulating C1q/TNF-related protein-12 levels are associated with the severity of coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) is the world's largest cause of death. The association of CAD with inflammation is well established. Recently, it has been confirmed that the C1q/TNF-related protein 12 (CTRP12) has a great anti-inflammatory effect. However, few data are available regarding the serum CTRP12 concentration levels in CAD patients. OBJECTIVE: The study was performed to evaluate the correlation between the serum levels of CTRP12 and the CAD severity regarding to the number of affected vessels. METHODS: About 200 suspected CAD patients and 50 healthy ones as a control, were evaluated based on case-control study. According to the results of angiography, patients were divided into CAD+ (n = 150) with any major coronary artery stenosis ≥50% and CAD- (n = 50) with <50% stenosis of the arteries. The CAD+patients were categorized into one- (1VD), two- (2VD) and three-vessel disease (3VD) based on the number of stenotic vessels. In the current study, different parameters such as CTRP12, tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), total oxidant status (TOS), total antioxidant capacity (TAC), and malondialdehyde (MDA) levels were evaluated, and also lipid profiles, hs-CRP and demographic factors were investigated as well. RESULTS: Data revealed that CTRP12 and TAC levels in CAD + group were significantly lower than control subjects (P < 0.05). CTRP12 levels were found to be significantly lower in the 3VD compared with 1VD and 2VD subgroups (p < 0.01 and p < 0.05, respectively). CONCLUSION: Our results confirmed that serum CTRP12 level is inversely associated with CAD severity. Therefore, it may be used as a prediction marker for CAD.

A newly isolated Streptomyces rimosus strain capable of degrading deltamethrin as a pesticide in agricultural soil.

Chemical pesticides or insecticides with complex structures are highly abundant in the biosphere and have inevitable side effects on farmland, natural resources, and human health. Deltamethrin is the most popular and widely used pesticide that disrupts the cellular calcium channels. In the present study, isolated strains of bacteria were examined to determine the ones that were capable of degrading deltamethrin. Different species of bacteria were evaluated in terms of the capability to degrade deltamethrin. It is important to note that Streptomyces rimosus was able to degrade up to 200 mg/L deltamethrin concentration and could be grown in mineral salt medium agar containing deltamethrin to be used as a source of carbon and energy. The results demonstrated that there is a diversity of deltamethrin-degrading bacteria in agricultural soil ecosystems. The application of these bacteria, especially S. rimosus, might be used as a bioremediation technique to decrease pesticide contamination of the ecosystem.

Trastuzumab-monomethyl auristatin E conjugate exhibits potent cytotoxic activity in vitro against HER2-positive human breast cancer.

Targeted therapy using specific monoclonal antibodies (mAbs) conjugated to chemotherapeutic agents or toxins has become one of the top priorities in cancer therapy. Antibody-drug conjugates (ADCs) are emerging as a promising strategy for cancer-targeted therapy. In this study, trastuzumab, a humanized monoclonal anti-HER2 antibody, was reduced by dithiothreitol and conjugated to the microtubule-disrupting agent monomethyl auristatin E (MMAE) through a valine-citrulline peptide linker (trastuzumab-MC-Val-Cit-PABC-MMAE [trastuzumab-vcMMAE]). After conjugation, ADCs were characterized by using UV-vis, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and flow cytometry. The antitumor activity of the ADC was evaluated in breast cancer cells in vitro. In addition, ADCs were further characterized using purification by the protein A chromatography, followed by assessment using apoptosis and MTT (3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assays. Hydrophobic interaction chromatography was used to determine drug-to-antibody ratio species of ADCs produced. Our finding showed that approximately 5.12 drug molecules were conjugated to each mAb. H2L2, H2L, HL, H2, H, and L forms of ADCs were detected in nonreducing SDS-PAGE. The binding of trastuzumab-vcMMAE to HER2-positive cells was comparable with that of the parental mAb. The MTT assay showed that our ADCs induced significant cell death in HER2-positive cells, but not in HER2-negative cells. The ADCs produced was a mixture of species, unconjugated trastuzumab (14.147%), as well as trastuzumab conjugated with two (44.868%), four (16.886%), six (13.238%), and eight (10.861%) molecules of MMAE. These results indicated that MMAE-conjugated trastuzumab significantly increases the cytotoxic activity of trastuzumab, demonstrating high affinity, specificity, and antitumor activity in vitro. Trastuzumab-vcMMAE is an effective and selective agent for the treatment of HER2-positive breast tumors.

Antibody-drug conjugates (ADCs) for cancer therapy: Strategies, challenges, and successes.

Targeted delivery of therapeutic molecules into cancer cells is considered as a promising strategy to tackle cancer. Antibody-drug conjugates (ADCs), in which a monoclonal antibody (mAb) is conjugated to biologically active drugs through chemical linkers, have emerged as a promising class of anticancer treatment agents, being one of the fastest growing fields in cancer therapy. The failure of early ADCs led researchers to explore strategies to develop more effective and improved ADCs with lower levels of unconjugated mAbs and more-stable linkers between the drug and the antibody, which show improved pharmacokinetic properties, therapeutic indexes, and safety profiles. Such improvements resulted in the US Food and Drug Administration approvals of brentuximab vedotin, trastuzumab emtansine, and, more recently, inotuzumab ozogamicin. In addition, recent clinical outcomes have sparked additional interest, which leads to the dramatically increased number of ADCs in clinical development. The present review explores ADCs, their main characteristics, and new research developments, as well as discusses strategies for the selection of the most appropriate target antigens, mAbs, cytotoxic drugs, linkers, and conjugation chemistries.

Gelatin-based nanoparticles and antibiotics: a new therapeutic approach for osteomyelitis?

The result of infection of bone with microorganisms is osteomyelitis and septic arthritis. Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for most of its cases (more than 50%). Since MRSA is resistant to many treatments, it is accompanied by high costs and numerous complications, necessitating more effective new treatments. Recently, development of gelatin nanoparticles have attracted the attention of scientists of biomedicine to itself, and have been utilized as a delivery vehicle for antibiotics because of their biocompatibility, biodegradability, and cost-effectiveness. Promising results have been reported with gelatin modification and combinations with chemical agents. Although these findings have been suggested that gelatin has the potential to be a suitable option for continuous release of antibiotics in osteomyelitis and septic arthritis treatment, they still have not become routine in clinical practices. The most deliver antibiotic using gelatin-derived composites is vancomycin which is showed the good efficacy. To date, a number of pre-clinical studies evaluated the utility of gelatin-based composites in the management of osteomyelitis. Gelatin-based composites were found to have satisfactory performance in the control of infection, as well as the promotion of bone defect repair in chronic osteomyelitis models. This review summarized the available evidence which provides a new insight into gelatin-derived composites with controlled release of antibiotics.

Enhancement of cisplatin-induced apoptosis by saffron in human lung cancer cells.

BACKGROUND: Cisplatin is a prevalent chemotherapeutic agent, and it has been used extensively to treat lung cancer. However, its clinical efficacy is hampered by its safety profile and dose-limiting toxicity. Saffron is a natural product that has shown significant anticancer effects. The combination treatment of saffron with chemotherapeutic agents has been considered a new strategy. METHODS: Herein, saffron extract as a natural anticancer substance was combined with cisplatin to assess their combined efficacy against tumor development in vitro. In A549 and QU-DB cell lines, the combined effect of the saffron extract with cisplatin led to a significant reduction in cell viability as compared to cisplatin alone. RESULTS: After 48 h incubation a considerable reduction in ROS levels in the QU-DB cell line upon treatment with cisplatin in the presence of saffron extract in comparison with cells treated with cisplatin alone. Furthermore, apoptosis increased significantly when in cells treated with cisplatin in combination with saffron extract compared to cisplatin alone. CONCLUSION: Our data establish that the combination of saffron extract as a natural anticancer substance with cisplatin leads to improved cell toxicity of cisplatin as an anticancer agent. Therefore, the saffron extract could be potentially used as an additive to enable a reduction in cisplatin dosages and its side effects.

A review of the protective effects of quercetin-rich natural compounds for treating ischemia-reperfusion injury.

Ischemia-reperfusion (IR) injury causes dysfunction of tissues and organs, and oxidative stress plays an important role. During IR, reactive oxygen species (ROS) are increased. Antioxidants are used to decrease ROS associated with IR. We review the protective effects of quercetin-rich natural antioxidants against IR. We searched PubMed, ScienceDirect, Scopus and Cochrane databases using the keywords: ischemic reperfusion, quercetin, antioxidant and herbal medicine. The effects of quercetin during IR have been reported for animal models in vitro and in vivo. Quercetin-rich plants including Abelmoschus esculentus, coriander, Hypericum perforatum, onion, Psidium guajava, buckwheat and Rosa laevigata Michx have been used to reduce oxidative stress damage to various organs during IR.

Simultaneous silencing of the A2aR and PD-1 immune checkpoints by siRNA-loaded nanoparticles enhances the immunotherapeutic potential of dendritic cell vaccine in tumor experimental models.

Following various immunotherapies, lack of proper anti-tumor immune responses is considered a significant problem in novel cancer therapeutic approaches. The expression of inhibitory checkpoint molecules on tumor-infiltrating T cells is one of the main reasons for the ineffectiveness of various immunotherapies. Therefore, we decided to inhibit two of the most important immune checkpoints expressed on tumor-associated T cells, PD-1 and A2aR. Ligation of PD-1 with PD-L1 and A2aR with adenosine significantly suppress T cell responses against tumor cells. Whitin tumors, specific inhibition of these molecules on T cells is of particular importance for successful immunotherapy as well as the elimination of treatment-associated side-effects. Thus, in this study, superparamagnetic iron oxide (SPION) nanoparticles (NPs) were covered by chitosan lactate (CL), functionalized with TAT peptide, and loaded with siRNA molecules against PD-1 and A2aR. Appropriate physicochemical properties of the prepared NPs resulted in efficient delivery of siRNA to tumor-derived T cells and suppressed the expression of A2aR and PD-1, ex vivo. T cell functions such as cytokine secretion and proliferation were considerably enhanced by the downregulation of these molecules which led to an increase in their survival time. Interestingly, treatment of CT26 and 4T1 mouse tumors with siRNA-loaded NPs not only inhibited tumor growth but also markedly increased anti-tumor immune responses and survival time. The results strongly support the efficacy of SPION-CL-TAT NPs loaded with anti-PD-1/A2aR siRNAs in cancer therapy and their further development for cancer patients in the near future.

Protective Effects of Hydroalcoholic Extract of Rosa canina Fruit on Vancomycin-Induced Nephrotoxicity in Rats.

Vancomycin-induced nephrotoxicity (VIN) has been reported to occur in 5-35% of recipient patients. The aims of the study were to evaluate protective effects of Rosa canina (RC) on VIN in rats. Rats were randomly divided into five groups as follows: control group I, group II (received VAN 400 mg/kg/day, every 12 h at doses of 200 mg/kg/day, for 7 consecutive days), group III (VAN + RC 250 mg/kg/day, for 7 consecutive days), group IV (VAN + RC 500 mg/kg/day, for consecutive days), and group V (received RC 500 mg/kg/day, for consecutive 7 days). On the eighth day after anesthetizing the animals, blood samples were taken from the heart, and then, the kidneys were removed to investigate kidney function, oxidative stress, and histopathological marker. Also, the chemical composition of RC extract was identified by GC-MS analysis. Oral dose of 500 mg/kg RC extract significantly reduced the serum levels of blood urea nitrogen (BUN), creatinine (Cr), malondialdehyde (MDA), and nitric oxide (NO) and also the kidney tissue MDA, protein carbonyl, and NO metabolites (nitrite) levels compared to the VAN-treated group (P < 0.05). Based on histopathological analysis, RC extract at the dose of 500 mg/kg inhibited the destructive effects of VAN on kidney tissues. GC-MS analysis indicated that the main compositions were found to be lactose (21.96%), 3-t-butyloxaziridine (20.91%), and 5-oxymethylfurfurole (16.75%). The results indicated that oral administration of RC was able to reduce VAN-induced nephrotoxicity in rats, possibly through antioxidant pathways.

Resveratrol: A New Potential Therapeutic Agent for Melanoma?

Melanoma is the most life-threatening and aggressive class of skin malignancies. The incidence of melanoma has steadily increased. Metastatic melanoma is greatly resistant to standard antimelanoma treatments such as chemotherapy, and the 5-year survival rate of cases with melanoma who have a metastatic form of the disease is less than 10%. The contributing role of apoptosis, angiogenesis and autophagy in the pathophysiology of melanoma has been previously demonstrated. Thus, it is extremely urgent to search for complementary therapeutic approaches that could enhance the quality of life of subjects and reduce treatment resistance and adverse effects. Resveratrol, known as a polyphenol component present in grapes and some plants, has anti-cancer properties due to its function as an apoptosis inducer in tumor cells, and anti-angiogenic agent to prevent metastasis. However, more clinical trials should be conducted to prove resveratrol efficacy. Herein, for the first time, we summarize the current knowledge of anti-cancerous activities of resveratrol in melanoma.

Targeted Delivery of CRISPR/Cas13 as a Promising Therapeutic Approach to Treat SARS-CoV-2.

On a worldwide scale, the outbreak of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to extensive damage to the health system as well as the global economy. Hitherto, there has been no approved drug or vaccine for this disease. Therefore, the use of general antiviral drugs is at the first line of treatment, though complicated with limited effectiveness and systemic side effects. Given the pathophysiology of the disease, researchers have proposed various strategies not only to find a more specific therapeutic way but also to reduce the side effects. One strategy to accomplish these goals is to use CRISPR/Cas13 system. Recently, a group of scientists has used the CRISPR/Cas13 system, which is highly effective in eliminating the genome of RNA viruses. Due to the RNA nature of the coronavirus genome, it seems that this system can be effective against the disease. The main challenge regarding the application of this system is to deliver it to the target cells efficiently. To solve this challenge, it seems that using virosomes with protein S on their membrane surface can be helpful. Studies have shown that protein S interacts with its specific receptor in target cells named Angiotensin-Converting Enzyme 2 (ACE2). Here, we propose if CRISPR/Cas13 gene constructs reach the infected cells efficiently using a virosomal delivery system, the virus genome will be cleaved and inactivated. Considering the pathophysiology of the disease, an important step to implement this hypothesis is to embed protein S on the membrane surface of virosomes to facilitate the delivery of gene constructs to the target cells.

The Effect of the Hydroalcoholic Extract of Watercress on the Levels of Protein Carbonyl, Inflammatory Markers, and Vitamin E in Chronic Hemodialysis Patients.

INTRODUCTION: Chronic kidney disorder is a main public health concern. Inflammatory processes and oxidative stress are common in end-stage renal disease patients. We aimed to evaluate the effect of the hydroalcoholic extract of watercress (WC) on the inflammatory cytokines and protein carbonyl (PCO) contents in chronic hemodialysis patients. METHODS: This was a double-blind randomized clinical trial performed on 46 hemodialysis patients. The participants were randomly divided into two groups: intervention group (500 mg hydroalcoholic extract of WC every day for 4 weeks) and control group (500 mg of white flour every night for 4 weeks). The blood samples were taken to determine the levels of vitamin E, PCO, and inflammatory cytokines at baseline and the end of treatment. RESULTS: Forty-five patients completed the study (22 patients in the intervention group and 23 patients in the control group). There was a significant reduction in the PCO level (20.33 ± 4.40 vs. 15.06 ± 6.41, P=0.001) in the intervention group; also, this change was statistically significant relative to the control group. Furthermore, there were significant reductions in hs-CRP (8953.30 ± 5588.06 vs. 7249.86 ± 5091.62, P=0.007) and IL-6 (60.10 (55.99, 73.10) vs. 55.21 (53.39, 60.48), P=0.050) in the intervention group, but these changes were not significant in comparison with the control group. CONCLUSION: We conclude that the hydroalcoholic extract of WC reduced the PCO content in hemodialysis patients via inhibition of protein oxidation. Although WC administration had caused a significant reduction in IL-6 and CRP levels, these differences were not statistically significant relative to the control group. Further research is needed to identify the antioxidant and anti-inflammatory effects of WC in hemodialysis patients.

Different T cell related immunological profiles in COVID-19 patients compared to healthy controls.

In various pathological conditions, cellular immunity plays an important role in immune responses. Amongimmunecells, T lymphocytes pdomotecellular and humoralresponses as well as innate immunity. Therefore, careful investigation of these cells has a significant impact on accurate knowledge in COVID-19diseasepathogenesis. In current research, the frequency and function of various T lymphocytes involved in immune responses examined in SARS-CoV-2 patients with various disease severity compared to normal subjects. In order to make an accurate comparison among patients with various disease severity, this study was performed on asymptomatic recovered cases (n = 20), ICU hospitalized patients (n = 30), non-ICU hospitalized patients (n = 30), and normal subjects (n = 20). To precisely evaluate T cells activity following purification, their cytokine secretion activity was examined. Similarly, immediately after purification of Treg cells, their inhibitory activity on T cells was investigated. The results showed that COVID-19 patients with severe disease (ICU hospitalized patients) not only had a remarkable increase in Th1 and Th17 but also a considerable decrease in Th2 and Treg cells. More importantly, as the IL-17 and IFN-γ secretion was sharply increased in severe disease, the secretion of IL-10 and IL-4 was decreased. Furthermore, the inhibitory activity of Treg cells was reduced in severe disease patients in comparison to other groups. In severe COVID-19 disease, current findings indicate when the inflammatory arm of cellular immunity is significantly increased, a considerable reduction in anti-inflammatory and regulatory arm occurred.

Effect of Boswellia species on the metabolic syndrome: A review.

The metabolic syndrome, a cluster of metabolic disorders, includes abdominal obesity, hypertension, dyslipidemia, and hyperglycemia leading to insulin resistance, development of diabetes mellitus, and cardiovascular diseases. For the treatment of metabolic syndrome, traditional herbal medicines such as frankincense or Boswellia species have been used due to their anti-inflammatory, anti-oxidant, anti-obesity, antidiabetic, antihypertensive, and hypolipidemic properties. Based on the literature, published evidence up to 2020 about the therapeutic effects of Boswellia species on the metabolic disorder among Medline, Scopus, and Google Scholar were precisely evaluated by keywords such as obesity, diabetes, hyperglycemia, hypertension, blood pressure, dyslipidemia, metabolic syndrome, frankincense, and Boswellia. According to the results, Boswellia species have beneficial effects to control metabolic syndrome and its related disorders such as hyperglycemia, dyslipidemia, hypertension, obesity, diabetes, and its complications. Boswellia species by reducing the resistance to insulin and restoring pancreatic beta cells decrease blood glucose. Also, Boswellia species has antithrombotic and anticoagulant properties that regulate blood pressure. The anti-oxidant properties of Boswellia species modulate the blood lipid profile via reducing TNF-α, IL-1ß levels, and increasing the adiponectin level. The therapeutic and protective effects of Boswellia species on metabolic disorders were remarkably confirmed regarding decreasing hyperglycemia, hyperlipidemia, hypertension, and obesity.

Antioxidant and protective effect of Stachys pilifera Benth against nephrotoxicity induced by cisplatin in rats.

The aim of current study was to assess the antioxidant and renoprotective effects of Stachys pilifera Benth (S.P.B.) hydroalcoholic extract on nephrotoxicity induced with cisplatin (CP). Adult rats with bodyweight of 180-220 g were divided into five groups (n = 7) treated as follows: group 1, control; group 2, CP; group 3, pretreatment with S.P.B. before CP; group 4, posttreatment with S.P.B. after CP; and, group 5, S.P.B. extract. A single dose of CP (7 mg/kg) was intraperitoneally injected on the fifth day and hydroalcoholic extract of S.P.B. (500 mg kg-1  day-1 ) was orally administered. The levels of oxidative stress markers, biochemical tests, and histopathological staining were assayed in serum and renal tissue. Also, the chemical composition of S.P.B. extract was determined by GC-MS analysis. The main compositions of S.P.B. extract identified by GC-MS analysis, were hexadeca-2,6,10,14-tetraen-1-ol, 3,7,11,16-tetramethyl (24.77%), thymol (14.1%), and linolenic acid (13.4%). In groups treated and pretreated with S.P.B., blood urea nitrogen, creatinine, malondialdehyde, and nitric oxide metabolite in serum as well as malondialdehyde and protein carbonyl content of kidney tissues were significantly decreased in comparison to CP group; in contrast, total thiol group showed a significant increase in treated group as compared to CP group. Furthermore, histological investigation indicated that treatment with S.P.B. improved renal damages induced by CP. The current study showed that S.P.B. hydroalcoholic extract improved the biochemical parameters and kidney function as well as restored antioxidant activity in CP-induced nephrotoxicity. However, it needs more investigations to define the mechanism of S.P.B. action. PRACTICAL APPLICATIONS: In different regions of Iran, Stachys is demonstrated by 34 species, out of which 13 are endemic, one of these endemic species is Stachys pilifera Benth (S.P.B.). The oil of S.P.B. is mainly consisted of cis-chrysanthenyl acetate, cis-chrysanthenol, spathulenol, ß-caryophyllene, linalool, and terpinen-4-ol. Moreover, phytochemical studies have shown the presence of compounds such as diterpenes, phenylethanoid glycosides, saponins, terpenoides, and flavonoids in Stachys species. The aerial parts of S.P.B. are consumed as herbal tea to treat several disorders, for example, infections, asthma, and rheumatoid arthritis in Iranian folk medicine. The aim of current study was to evaluate the antioxidant and protective effects of S.P.B. hydroalcoholic extract on nephrotoxicity induced with cisplatin (CP). The current study showed that S.P.B. hydroalcoholic extract improved the biochemical parameters and kidney function as well as restored antioxidant activity in CP-induced nephrotoxicity. However, it needs more researches to define the mechanism of S.P.B. action.

Circular RNA and Diabetes: Epigenetic Regulator with Diagnostic Role.

Circular RNAs, a group of endogenous non-coding RNAs, are characterized by covalently closed cyclic structures with no poly-adenylated tails. It has been recently recommended that cirRNAs have an essential role in regulating genes expression by functioning as a translational regulator, RNA binding protein sponge and microRNA sponge. Due to their close relation to the progression of various diseases such as diabetes, circRNAs have become a research hotspot. A number of circRNAs (i.e., circRNA_0054633, circHIPK3, circANKRD36, and circRNA11783-2) have been shown to be associated with initiation and progression of diabetes. Based on reports, in a tissue, some circRNAs are expressed in a developmental stage-specific manner. In this study, we reviewed research on circular RNAs involved in the pathogenesis and diagnosis of diabetes and their prognostic roles.

CXCL-10: a new candidate for melanoma therapy?

BACKGROUND: Melanoma is a malignancy that stems from melanocytes and is defined as the most dangerous skin malignancy in terms of metastasis and mortality rates. CXC motif chemokine 10 (CXCL10), also known as interferon gamma-induced protein-10 (IP-10), is a small cytokine-like protein secreted by a wide variety of cell types. CXCL10 is a ligand of the CXC chemokine receptor-3 (CXCR3) and is predominantly expressed by T helper cells (Th cells), cytotoxic T lymphocytes (CTLs), dendritic cells, macrophages, natural killer cells (NKs), as well as some epithelial and cancer cells. Similar to other chemokines, CXCL10 plays a role in immunomodulation, inflammation, hematopoiesis, chemotaxis and leukocyte trafficking. CONCLUSIONS: Recent studies indicate that the CXCL10/CXCR3 axis may act as a double-edged sword in terms of pro- and anti-cancer activities in a variety of tissues and cells, especially in melanoma cells and their microenvironments. Most of these activities arise from the CXCR3 splice variants CXCR3-A, CXCR3-B and CXCR3-Alt. In this review, we discuss the pro- and anti-cancer properties of CXCL10 in various types of tissues and cells, particularly melanoma cells, including its potential as a therapeutic target.

The protective effects of silymarin on ischemia-reperfusion injuries: A mechanistic review.

Ischemia-reperfusion injuries (IRI) occur in different clinical conditions such as stroke, trauma, organ transplantation, and so on. Ischemia damages mainly arise from oxygen depletion in tissues. The lack of oxygen as the last acceptor of electron in the respiratory chain causes a decrease in ATP production and eventually leads to disruption of membrane transport, acidosis, cellular edema and membrane distortion of organelles, and cells. Reperfusion can intensify ischemic injuries by the infiltration of inflammatory cells and also oxygen and calcium overloading. Since the tissue antioxidant contents decreased due to increased generation of reactive oxygen species (ROS) during IRI, the application of antioxidants is considered an appropriate strategy to ameliorate IRI. Silymarin constitutes about 70-80% of silybum marianum dry extract and is known as a strong free radical scavenger with anti-inflammatory properties. In several studies, silibinin as a major component of Silymarin could provide protective effects in various tissue IRI by different mechanisms such as scavenging free radicals, decreasing inflammatory cytokines, inhibiting cellular death, and increasing the expression of antioxidant enzymes. To clarify functional mechanisms, the present article evaluates studies about silymarin effects in different tissues IRI.

Hepatoprotective and antioxidant activity of watercress extract on acetaminophen-induced hepatotoxicity in rats.

INTRODUCTION: Acetaminophen (APAP) as an analgesic and antipyretic drug can result to liver damages while using more than 4 g/day. Therefore, APAP toxicity causes the liver to dysfunction. This study aims to investigate the hepatoprotective and antioxidant activity of hydroalcoholic extract of watercress (WC) in APAP-induced hepatotoxicity in rats. MATERIALS AND METHODS: Randomly, twenty-four Wistar rats were divided into four groups of six each. Groups named as control, APAP, APAP + WC and APAP + S for group 1, 2, 3, and 4, respectively. Group 1 received distilled water 1 ml/kg for 7 days. In group 2, 3, and 4, rats pretreated by receiving distilled water (1 ml/kg), WC extract (500 mg/kg), silymarin extract (mg/kg) for 7 days, respectively. Of note, to induce acute hepatotoxicity in groups 2, 3, and 4, rats posttreated by orally intoxicated with single dose of APAP (2 g/kg) on the sixth day. The animals were sacrificed on the seventh day. Alanine amino transferase (ALT), aspartate amino transferase (AST), ferric reducing ability of plasma (FRAP), protein carbonyl (PCO), total thiol (T-SH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities were measured in plasma. It should be noted that the chemical composition of WC extract was identified by GC-MS analysis. RESULTS: The results have shown that there was a significant increase in AST, ALT, FRAP and PCO content in APAP group in comparison to control. Also, there was a significant reduction in T-SH levels and GPx activity in APAP group compared to control. However, administration of WC extract and silymarin not only causes a significant decrease in AST activity, but they markedly increased T-SH content and GPx activity compared to APAP group. GC-MS analysis showed the major compositions were found to be benzenepropanenitrile (48.30 %), Phytol (10.10 %), α-cadinene (9.50%) and linolenic acid (8.0). CONCLUSIONS: It is concluded that the WC extract reduces APAP-induced toxicity through its hepatoprotective and antioxidant activity in rats.