Leptin/lipopolysaccharide-treated dendritic cell vaccine improved cellular immune responses in an animal model of breast cancer.

PURPOSE: In dendritic cells (DCs), leptin as an immune-regulating hormone, increases the IL-12 generation whereas it reduces the IL-10 production, thus contributing to TH1 cell differentiation. Using a murine model of breast cancer (BC), we evaluated the impacts of the Leptin and/or lipopolysaccharide (LPS)-treated DC vaccine on various T-cell-related immunological markers. MATERIALS AND METHODS: Tumors were established in mice by subcutaneously injecting 7 × 105 4T1 cells into the right flank. Mice received the DC vaccines pretreated with Leptin, LPS, and both Leptin/LPS, on days 12 and 19 following tumor induction. The animals were sacrificed on day 26 and after that the frequency of the splenic cytotoxic T lymphocytes (CTLs) and TH1 cells; interferon gamma (IFN-γ), interleukin 12 (IL-12) and tumor growth factor beta (TGF-ß) generation by tumor lysate-stimulated spleen cells, and the mRNA expression of T-bet, FOXP3 and Granzyme B in the tumors were measured with flow cytometry, ELISA and real-time PCR methods, respectively. RESULTS: Leptin/LPS-treated mDC group was more efficient in blunting tumor growth (p = .0002), increasing survival rate (p = .001), and preventing metastasis in comparison with the untreated tumor-bearing mice (UT-control). In comparison to the UT-control group, treatment with Leptin/LPS-treated mDC also significantly increased the splenic frequencies of CTLs (p < .001) and TH1 cells (p < .01); promoted the production of IFN-γ (p < .0001) and IL-12 (p < .001) by splenocytes; enhanced the T-bet (p < .05) and Granzyme B (p < .001) expression, whereas decreased the TGF-ß and FOXP3 expression (p < .05). CONCLUSION: Compared to the Leptin-treated mDC and LPS-treated mDC vaccines, the Leptin/LPS-treated mDC vaccine was more effective in inhibiting BC development and boosting immune responses against tumor.

Glucosinolates in cancer prevention and treatment: experimental and clinical evidence.

Glucosinolates are naturally occurring ß-d-thioglucosides that mainly exist in the Brassicaceae family. The enzyme myrosinase hydrolyzes glucosinolates to form isothiocyanates, which are chemical protectors. Phenethyl isothiocyanate, sulforaphane, and benzyl isothiocyanate are potential isothiocyanate with efficient anti-cancer effects as a protective or treatment agent. Glucosinolate metabolites exert the cancer-preventive activity through different mechanisms, including induction of the Nrf2 transcription factor, inhibition of expression of tumor necrosis factor-α (TNFα) and interleukin-1ß (IL-1ß), induction of apoptosis through inhibiting phase I enzymes and inducting phase II enzymes, interruption of caspase pathways, STAT1/STAT2, inhibition of sulfotransferases. Moreover, glucosinolates and their metabolites are effective in cancer treatment by inhibiting angiogenesis, upregulating natural killers, increasing expression of p53, p21, caspase 3 and 9, and modulating NF-κB. Despite the mentioned cancer-preventing effects, some isothiocyanates can increase the risk of tumors. So, further studies are needed to obtain an accurate and effective dose for each glucosinolates to treat different types of tumors.

Distinct signatures on d-galactose-induced aging and preventive/protective potency of two low-dose vitamin D supplementation regimens on working memory, muscular damage, cardiac and cerebral oxidative stress, and SIRT1 and calstabin2 downregulation.

Chronic administration of d-galactose (d-gal) in rodents reproduces the overproduction of reactive oxygen species of physiological aging. The present research shows for the first time distinct signatures on d-gal-induced aging (500 mg/kg, 6 weeks) and the preventive and protective potential of two vitamin D (50 IU) supplementation regimens (pre-induction and simultaneous, respectively) in two vital organs (heart and brain). d-gal-induced notorious alterations in working memory, a strong increase in brain malondialdehyde (MDA) oxidative levels, and strong downregulation of sirtuin 1 (SIRT1) in the heart and hippocampus and of calstabin2 in the heart. Cardiac and brain superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymatic antioxidant capacities were damaged, brain calstabin2 was downregulated, and neuropathology was observed. Heart damage also included a moderate increase in MDA levels, serologic lactate dehydrogenase (LDH), total creatine kinase (CK) activities, and histopathological alterations. The used dose of vitamin D was enough to prevent cognitive impairment, avoid muscular damage, hamper cardiac and cerebral oxidative stress, and SIRT1 and calstabin2 downregulation. Most importantly, the potencies of the two preventive schedules depended on the tissue and level of study. The pre-induction schedule prevented d-gal-induced aging by 1 order of magnitude higher than simultaneous administration in all the variables studied except for SIRT1, whose strong downregulation induced by d-gal was equally prevented by both schedules. The benefits of vitamin D for oxidative stress were stronger in the brain than in the heart. Brain MDA levels were more sensitive to damage, while SOD and GPx antioxidant enzymatic activities were in the heart. In this order, the magnitude of SOD, MDA, and GPx oxidative stress markers was sensitive to prevention. In summary, the results unveiled distinct aging induction, preventive signatures, and sensitivity of markers depending on different levels of study and tissues, which are relevant from a mechanistic view and in the design of targeted interventions.

Vaccination with celecoxib-treated dendritic cells improved cellular immune responses in an animal breast cancer model.

PURPOSE: Prostaglandin E2 (PGE2), a product of cyclooxygenase (COX) pathway of arachidonic acid, exerts inhibitory impacts on dendritic cell (DC) activity to repress anti-tumor immune responses. Therefore, targeting COX during DC vaccine generation may enhance DC-mediated antitumor responses. We aimed to investigate the impacts of DC vaccine treated with celecoxib (CXB), a selective COX2 inhibitor, on some T cell-related parameters. MATERIALS AND METHODS: Breast cancer (BC) was induced in BALB/c mice, and then they received DC vaccine treated with lipopolysaccharide (LPS-mDCs), LPS with a 5 â€‹µM dose of CXB (LPS/CXB5-mDCs) and LPS with a 10 â€‹µM dose of CXB (LPS/CXB10-mDCs). The frequency of splenic Th1 and Treg cells and amounts of IFN-γ, IL-12 and TGF-ß production by splenocytes, as well as, the expression of Granzyme-B, T-bet and FOXP3 in tumors were determined using flow cytometry, ELISA, and real-time PCR, respectively. RESULTS: Compared with untreated tumor group (T-control), treatment with LPS/CXB5-mDCs and LPS/CXB10-mDCs decreased tumor growth (P â€‹= â€‹0.009 and P â€‹< â€‹0.0001), escalated survival rate (P â€‹= â€‹0.002), increased the frequency of splenic Th1 cells (P â€‹= â€‹0.0872, and P â€‹= â€‹0.0155), increased the IFN-γ (P â€‹= â€‹0.0003 and P â€‹= â€‹0.0061) and IL-12 (P â€‹= â€‹0.001 and P â€‹= â€‹0.0009) production by splenocytes, upregulated T-bet (P â€‹= â€‹0.062 and P â€‹< â€‹0.0001) and Granzyme-B (P â€‹= â€‹0.0448 and P â€‹= â€‹0.4485), whereas decreased the number of Treg cells (P â€‹= â€‹0.0014, and P â€‹= â€‹0.0219), reduced the amounts of TGF-ß production by splenocytes (P â€‹= â€‹0.0535 and P â€‹= â€‹0.0169), and reduced the expression of FOXP3 (P â€‹= â€‹0.0006 and P â€‹= â€‹0.0057) in comparison with T-control group. CONCLUSIONS: Our findings show that LPS/CXB-treated DC vaccine potently modulated antitumor immune responses in a mouse BC model.

The Effects of Clove and Its Constituents on Reproductive System: a Comprehensive Review.

Clove with the scientific name of Syzygium aromaticum (L.) Merr. & L.M. Perry is an evergreen tree in which its buds are used for medicinal purposes. Traditional medicine manuscripts as well as recent studies reported its effects on male and female reproductive systems. The aim of this study is to investigate the reported contradictory effects of clove and its phytochemicals on the reproductive system of both males and females. All types of in vitro, animal, and human studies of clove and its main constituents in the field of reproductive systems were collected via searching electronic databases including PubMed and Scopus from the onset till 2021. In this review, 76 articles were included, of which 25 were related to male reproduction, 32 were related to female reproduction, and 19 were related to reproductive malignancies. Analysis of the literature indicates the effects of clove and its constituents especially eugenol and ß-caryophyllene on the level of sex hormones, fertility, sperm abnormalities, endometriosis, menstrual cycle, as well as gynecological infections, and reproductive tumors. The main mechanism of clove has not been understood yet but it seems that different parameters affect its pharmacological activity including the type of extract, dose, and duration of administration as well as the primary cause of the disorder. According to the effects of clove on different parts of the reproductive system, it seems that it can be a suitable candidate for related disorders, provided that more and more detailed studies are done on it.

Cimetidine and Ibuprofen Modulate T Cell Responses in a Mouse Model of Breast Cancer.

Cimetidine and ibuprofen exhibit immunomodulatory effects as an antagonist of histamine H2 receptor, and a cyclooxygenase inhibitor, respectively. Here, the effects of cimetidine and ibuprofen on some effector T cell-related parameters were investigated using a breast cancer (BC) model. BC was established in Balb/c mice using the 4T1 cell line. On day 10 after tumor induction, the BC-bearing mice were classified into four groups and treated with PBS, cimetidine (20 mg/kg), ibuprofen (20 mg/kg) or a combination of "cimetidine + ibuprofen" via intraperitoneal injection (daily from days 11 to 30). The mice were sacrificed on day 31 and the frequency of splenic Th1 and Treg cells, plasma IFN-γ and TGF-ß levels, and intra-tumoral T-bet, GATA3, FOXP3 and RORγt expressions were detected using flowcytometry, ELISA and real-time-PCR, respectively. In untreated cancerous mice, the percentage of splenic Th1 cells and plasma IFN-γ levels were lower (P<0.003 and P<0.01, respectively), whereas the percentage of splenic Treg cells and plasma TGF-ß levels were higher than in healthy mice (P<0.04 and P<0.005, respectively). Treatment of BC-bearing mice with cimetidine, ibuprofen or both drugs promoted the frequency of Th1 cells (P<0.05, P<0.007 and P<0.005, respectively) as well as IFN-γ levels (P<0.004, P<0.0001 and P<0.03, respectively), while reduced the frequencies of Treg cells (P<0.02, P<0.03 and P<0.01, respectively), TGF-ß levels (P<0.006, P<0.02 and P<0.002, respectively), intra-tumoral expression of FOXP3 (P<0.006, P<0.005 and P<0.005, respectively), and intra-tumoral expression of RORγt (P<0.04, P<0.03 and P<0.05, respectively) compared with untreated BC mice. The "cimetidine + ibuprofen"-treated mice displayed greater T-bet expression than the un-treated mice (P<0.006). Cimetidine and/or ibuprofen-treated BC-bearing mice exhibited reduced intra-tumoral expression of GATA3 compared with the untreated BC mice, but the differences were not significant. Cimetidine and ibuprofen correct some effector T cell-related parameters in cancerous mice. Immunotherapeutic potentials cimetidine and ibuprofen in cancers need investigations.

Investigation of the effect of IFN-γ/TNF-α-treated mesenchymal stem cells on Th9- and Treg cell-related parameters in a mouse model of ovalbumin-induced allergic asthma.

OBJECTIVE: Th9- and regulatory T (Treg) cells exert pro- and anti-allergic activity, respectively. Mesenchymal stem cell (MSC)-related immunomodulatory impacts can be enhanced by inflammatory cytokines. Here, the modulatory effects of IFN-γ/TNF-α-induced MSCs on Th9- and Treg cell-related parameters were investigated using an asthma model. METHODS: Allergic asthma was induced in BALB/c mice using sensitized and challenging with ovalbumin (OVA). The asthmatic groups were treated intraperitoneally with PBS, MSCs, IFN-γ-induced MSCs, TNF-α-induced MSCs and 'IFN-γ + TNF-α'-induced MSCs before the challenge phase. The mice were sacrificed 24 h after challenge. The serum IL-9 and IL-35 levels, as well as gene expression of IL-9, PU.1, IL-35-EBI3, and FOXP3 in the lung tissues were assessed using ELISA and real time-PCR, respectively. RESULTS: The differences of Th9 and Treg-related parameters were not significant between untreated asthmatic mice and those treated with non-induced MSCs. In comparison with untreated asthmatic group, treatment with IFN-γ-induced MSCs significantly reduced serum IL-9 levels, reduced lung expression of IL-9 and PU.1, while increasing serum IL-35 levels as well as lung expression of FOXP3; treatment with TNF-α-induced MSCs significantly reduced serum IL-9 levels as well as lung expression of IL-9, and treatment with 'IFN-γ + TNF-α'-induced MSCs, significantly modulated all investigated Th9 and Treg-related parameters. In comparison to mice treated with non-induced MSCs, serum IL-9 levels were remarkably decreased in mice treated with IFN-γ-induced and 'IFN-γ + TNF-α'-induced MSCs. CONCLUSIONS: IFN-γ-and 'IFN-γ + TNF-α' treated MSCs exerted almost comparable impacts, but were more efficient than TNF-α-exposed MSCs. Thus, IFN-γ alone can be sufficient to promote immunomodulatory effects of MSCs.

Inhibition of apelin/APJ axis enhances the potential of dendritic cell-based vaccination to modulate TH1 and TH2 cell-related immune responses in an animal model of metastatic breast cancer.

PURPOSE: The immunosuppressive microenvironment of tumors reduces the effectiveness of immunotherapies. Apelin as an immunosuppressor peptide is expressed in the microenvironment of many tumors. Thus, inhibition of apelin-related protumor activities can promote the effectiveness of cancer immunotherapy. Here, we investigated the efficacy of a dendritic cell (DC) vaccine in combination with an apelin receptor antagonist, ML221, to modulate Th1 and Th2 cell-related responses in breast cancer-bearing mice. MATERIALS AND METHODS: Tumor was induced in female BALB/c mice by injecting 7 â€‹× â€‹105 4T1 cells in the right flank. Tumor-bearing mice were then given PBS, ML221, DC vaccine and "ML221 + DC vaccine" for 21 days. On day 37, mice were sacrificed and the frequency of Th1/Th2 cells in spleen and serum levels of IFN-γ/IL-10 were determined using flow cytometry and ELISA, respectively. Lung metastasis was evaluated in lung tissues stained with hematoxylin and eosin. Finally, the obtained data were analyzed using appropriate statistical tests. RESULTS: Combination therapy with ML221 + DC vaccination was more effective in reducing tumor growth (P â€‹< â€‹0.0001), preventing lung metastasis (P â€‹< â€‹0.0001) and increasing survival rate (P â€‹< â€‹0.01) compared to the control group. Moreover, combination treatment substantially increased the frequency of Th1 cells while decreasing the frequency of Th2 cells in the spleen compared to the control group (P â€‹< â€‹0.01). It also reduced serum levels of IL-10 compared with the control group (P â€‹< â€‹0.05). CONCLUSION: Our findings showed that combination therapy using ML221 + DC vaccine can be considered as an effective cancer therapeutic program to potentiate anti-tumor immune responses.

Attenuation of isoprenaline-induced myocardial infarction by Rheum turkestanicum.

BACKGROUND: Oxidative stress plays a major role in the pathogenesis of myocardial infarction. This study evaluated the cardioprotective effects of the hydroalcoholic extract of Rheum turkestanicum on isoprenaline-induced myocardial infarction (MI) in Wistar rats. METHODS: In this study, we used liquid chromatography-mass spectrometry to determine the active compounds present in the extract. Thirty rats were divided to 5 groups (6 rats in each group). The extract was administered orally at the doses of 100 and 300 mg/kg body weight and then a subcutaneous injection of isoprenaline (85 mg/kg) was administered on the 8th and 9th days. Serum levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and creatinine kinase (CPK) were measured using standard commercial kits. Serum activities of superoxide dismutase, catalase, and cardiac levels of thiol and lipid peroxidation were also determined. Hematoxylin and eosin were used for histopathological staining. RESULTS: Phytochemical analysis revealed the presence of 24 compounds in the hydro-ethanolic extract of R. turkestanicum. Isoprenaline increased malondialdehyde (4.002 ± 0178, P < 0.001) while decreased thiol content (101.7 ± 6.186, P < 0.001). Moreover, reduced activities of superoxide dismutase (139 ± 10.88, P < 0.001) and catalase (2.812 ± 0.215, P < 0.001), and elevated levels of LDH (1245 ± 62.28, P < 0.001), CPK (898 ± 23.06, P < 0.001) and CK-MB (697 ± 50.22, P < 0.001) were observed. Pretreatment with the R. turkestanicum extract significantly reduced cardiac markers and increased thiol content as well as the activity of antioxidant enzymes. The extract attenuated the histopathological changes induced by isoprenaline. CONCLUSION: According to the obtained results, R. turkestanicum may be an appropriate candidate to reduce isoprenaline-induced MI through modulation of oxidative stress. Administration of the extract attenuated cardiac enzymes following isoprenaline administration. The cardioprotective action of the extract can be attributed to the bioactive antioxidant ingredients of R. turkestanicum. To identify the precise mechanisms, further investigations are required.

Calcium dobesilate protects against d-galactose-induced hepatic and renal dysfunction, oxidative stress, and pathological damage.

Calcium dobesilate (CaD) is used for the treatment of diabetic retinopathy and nephropathy. This agent exerts antioxidant effects. In the present study, we evaluated the protective effects of oral administration of CaD against hepatorenal damages in a mice model of aging induced by d-galactose (d-gal). We used 28 male albino mice, which equally and randomly were divided into four groups as follows: intact, aging (d-gal at the dose of 500 mg/kg, p.o.), aging + CaD 50 (d-gal plus CaD at the dose of 50 mg/kg), and aging + CaD 100 (d-gal plus CaD at the dose of 100 mg/kg, p.o.). All drugs were administered orally once a day for 42 days. The liver and kidney damages were evaluated by measuring mass indices, levels of serum creatinine and blood urea nitrogen, and activities of serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase and by histopathological evaluation. Moreover, hepatic and renal tissue oxidant/antioxidant markers (malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase) were measured. The results showed that d-gal treatment induced significant oxidative stress in the kidney and liver that was paralleled by dysfunctions and histological alterations of these organs. CaD significantly improved the liver and kidney indices, implemented functional capacity of the liver and kidney, as well as decreased oxidative stress enhancing antioxidative enzyme activities. CaD treatment also inhibited the development of histological alterations of both kidney and liver. CaD might represent a promising therapeutic agent for the attenuation of hepatorenal injuries induced by aging.

The Effect of Phytosterols and Fatty Acids of Pistachio (Pistacia vera) Oil on Spermatogenesis and Histological Testis Changes in Wistar Adult Male Rats.

PURPOSE: Oilseeds and their related products are known to have various bioactive and health-promoting ingredients. In this research, we investigated the effects of phytosterols and fatty acids of Pistacia vera on spermatogenesis process and testis histological changes in Wistar male rats for the first time. MATERIALS AND METHODS: A total number of 64 adult male Wistar rats were divided randomly into eight groups including one control group, and seven test groups. Test groups received phytosterols, fatty acids, and pistachio oil orally for 30 days. Then, LH, FSH, and serum testosterone levels were determined. Also, the spermatogenesis process and changes in testicular tissue in rats were investigated. RESULTS: The results of this research suggest that phytosterols in doses of 10 and 50 mg/kg reduce the spermatogenesis process. Fatty acid in a low dose of 10 mg/kg increases spermatogenesis, but when a high dose of 50 mg/kg was used, it harmed the spermatogenesis process. When low levels of phytosterols and fatty acids are used simultaneously in dose 5 mg/kg, improvement in spermatogenesis process is observed but when these were used together in the dose of 25 mg/kg, the spermatogenesis process was disrupted. Using pistachio oil alone also improved spermatogenesis process. CONCLUSION: It seems that phytosterols reduce spermatogenesis at high and low doses, while fatty acids increase spermatogenesis when used in low doses and reduce this process when used in high doses. The use of fatty acids extracted from pistachios to treat infertility in men seems hopeful.

Modulatory Effects of Metformin Alone and in Combination with Cimetidine and Ibuprofen on T Cell-related Parameters in a Breast Cancer Model.

Metformin, cimetidine, and ibuprofen separately exhibit immunomodulatory and anti-tumorigenic effects. Herein, the impacts of metformin alone and in combination with cimetidine/ibuprofen on some Th1- and regulatory T (Treg) cell-related parameters were evaluated using a breast cancer (BC) model. For establishing the BC model, four groups of Balb/c mice were challenged with the carcinoma cell line. After 11-30 days post-induction, they were treated intraperitoneally (with metformin (200 mg/kg), "metformin plus cimetidine (20 mg/kg)"; "metformin plus ibuprofen (20 mg/kg)", or with all three drugs in mentioned doses. Untreated BC and without tumor mice were enrolled as control groups. On day 31, splenic Th1 and Treg cell frequencies, serum interferon-gamma (IFN-γ), and transforming growth factor-beta (TGF-ß) concentration, and intra-tumoral T-bet, TGF-ß, and forkhead box protein P3 (FOXP3) expression were measured; using flow cytometry, enzyme-linked immunosorbent assay (ELISA), and real-time-PCR, respectively. Treatment of the BC mice with metformin alone and in combination with cimetidine and/or ibuprofen enhanced the frequency of Th1 cells, and IFN-γ concentration, while it resulted in a decrease in the frequency of Treg cells, serum TGF-ß concentration, and the expression of FOXP3 and TGF-ß compared with un-treated BC mice. FOXP3 expression in the metformin-treated group was lower in mice who received combination therapy. Survival rate and body weight were increased, while tumor size and spleen index were reduced in mice treated with metformin alone and its combination with cimetidine and/or ibuprofen. No remarkable differences were found between metformin-treated mice and those who received combination therapies regarding Th1 and Treg cell percentages, TGF-ß expression, body weight, tumor size, and spleen index. The benefits of combinational therapy may be largely attributed to metformin. Immunotherapeutic potentials of metformin in cancers need further considerations.

Cinnamon and its possible impact on COVID-19: The viewpoint of traditional and conventional medicine.

The COVID-19 global epidemic caused by coronavirus has affected the health and other aspects of life for more than one year. Despite the current pharmacotherapies, there is still no specific treatment, and studies are in progress to find a proper therapy with high efficacy and low side effects. In this way, Traditional Persian Medicine (TPM), due to its holistic view, can provide recommendations for the prevention and treatment of new diseases such as COVID-19. The muco-obstruction of the airway, which occurs in SARS-CoV-2, has similar features in TPM textbooks that can lead us to new treatment approaches. Based on TPM and pharmacological studies, Cinnamomum verum (Darchini)'s potential effective functions can contribute to SARS-CoV-2 infection treatment and has been known to be effective in corona disease in Public beliefs. From the viewpoint of TPM theories, Cinnamon can be effective in SARS-CoV-2 improvement and treatment through its anti-obstructive, diuretic, tonic and antidote effects. In addition, there is pharmacological evidence on anti-viral, anti-inflammatory, antioxidant, organ-o-protective and anti-depression effects of Cinnamon that are in line with the therapeutic functions mentioned in TPM.Overall, Cinnamon and its ingredients can be recommended for SARS-CoV2 management due to multi-targeting therapies. This review provides basic information for future studies on this drug's effectiveness in preventing and treating COVID-19 and similar diseases.

The effect of royal jelly and silver nanoparticles on liver and kidney inflammation.

OBJECTIVE: Royal jelly (RJ) is a honey bee product for which, anti-inflammatory properties were shown in vitro. Nanoparticles, including nano-silver (NS), are plausible inflammation inducers that act by activation of immune cells and consequent production of pro-inflammatory cytokines. This project aimed to explore immunomodulatory effects of royal jelly and nano-silver on the kidney and liver. MATERIALS AND METHODS: In this project, 40 male rats were grouped as follows: 10 rats as controls, 10 rats treated with RJ; 10 rats treated with both NS and RJ and 10 rats treated with NS. Liver and kidney interleukin (IL)-1ß, -2, -6, and -33 levels were determined using commercial ELISA kits. RESULTS: RJ reduced kidney IL-6 levels in comparison to control and NS--RJ groups. RJ and NS reduced kidney and liver IL-1ß levels. Kidney IL-33 levels were decreased in the RJ and nano-silver groups in comparison to the NS--RJ group. CONCLUSION: Based on this study, it may be concluded that RJ together with NS can play anti-inflammatory roles and may affect the function of immune cells.

The Effect of Kiwifruit Therapeutics in the Treatment of Diabetic Foot Ulcer.

Diabetes mellitus is considered a silent disease with possible late chronic complications such as diabetic foot ulcer. This condition is managed by surgical debridement. To improve surgical outcome, some surgeons use proteolytic agents after surgery. Kiwifruit contains a type of proteolytic enzyme called actinidin that may play a role in the treatment of such complication. In the current study, we evaluate the role of kiwifruit extract in the treatment of diabetic foot ulcer. Eighteen diabetic foot ulcer patients were included in a randomized, double-blind clinical trial. The patients were divided randomly to control and experimental groups. Patients in the control group underwent daily wound dressing using base ointment (Eucerin). In the experimental group, we added kiwifruit extract to the standard wound dressing. Clinical data including general appearance of wound (according to recorded photographs before and after medical intervention) were analyzed using SPSS version 22. The mean wound area of the experimental group was significantly less than in the control group (P = .005) after 4 weeks of treatment. Comparison of the average of size difference, before and after the treatment in the experimental group and the control group, shows that kiwifruit can have a good impact on wound healing (P = .0001). In patients with diabetic foot ulcer, wound dressing using kiwifruit extract may help reduce time of treatment and may replace surgical debridement for some selected cases.

Investigation of grape sap on wingless/integrated and ß-catenin genes expression with histological factors on the hair follicle in rat.

BACKGROUND AND PURPOSE: Natural products are used to improve the damage caused by harmful reagents in various pathological situations. This study investigated the effect of grape sap as a natural product with antioxidant properties on follicle cell proliferation in bleomycin (as a chemotherapy agent with toxic effects on hair growth) treated rats skin. EXPERIMENTAL APPROACH: The bleomycin treated rats were administrated grape sap. Wingless/integrated (wnt) and ß-catenin gene expression as follicle proliferative markers were evaluated using real-time polymerase chain reaction. Furthermore, histological factors and total antioxidant capacity were evaluated. FINDINGS / RESULTS: The data showed that, grape sap increased the number of anagenic hair follicle in grape sap (100 mg/kg) group (P < 0.001), sebaceous glands (P < 0.001), blood vessel density (P < 0.001), and hair growth length (P < 0.001). Also, wnt and ß-catenin gene expression was elevated. The data showed that wnt and ß-catenin gene expression were elevated in grape sap treated animals versus bleomycin group (P < 0.01 and 0.001, respectively). CONCLUSION AND IMPLICATIONS: Our finding showed that grape sap can be effective in increasing hair growth a gains bleomycin toxic effects on skin hair growth.

Ceftriaxone improves hepatorenal damages in mice subjected to D-galactose-induced aging.

Ceftriaxone (CTX) is a third-generation cephalosporin antibiotic that has broad-spectrum antimicrobial activity. This agent also has anti-inflammatory and antioxidant characteristics. In the current study, the effects of CTX against hepatorenal damages in a D-galactose (DGL) induced aging model were investigated. We used twenty-eight male mice which equally and randomly were separated into four groups as follows: Control, DGL group (treated with 500 mg/kg/day DGL orally for six weeks), DGL + CTX group (treated with 500 mg/kg/day DGL orally plus 200 mg/kg/day CTX intraperitoneally for six weeks), and CTX group (treated with 200 mg/kg/day CTX intraperitoneally for six weeks). The liver and kidney function indices such as serum creatinine, blood urine nitrogen, alanine aminotransferase, and aspartate aminotransferase were measured. Also, levels of malondialdehyde, catalase, and glutathione peroxidase in hepatic and renal tissues were evaluated. Moreover, the expression profiles of interleukin 1 beta and tumor necrosis factor alpha were assessed. The liver and kidney tissues were assessed for histopathological lesions. The results showed that aging induced by DGL leads to abnormalities in functional indices of the liver and kidneys. DGL also induced significant oxidative stress and inflammation, as well as histopathological lesions, in these organs. CTX improved functional indices, as well as the parameters of oxidative stress and inflammation, compared with the DGL-treated animals. These results were also confirmed by histological evaluations of the liver and kidneys. These data provide evidence for the therapeutic value of CTX in clinical practice for mitigating the hepatorenal damages of aging.

Ceftriaxone improves senile neurocognition damages induced by D-galactose in mice.

OBJECTIVES: Ceftriaxone (Cef), a beta-lactam antibiotic, is accompanied by antioxidant and anti-inflammatory properties. It has been shown that Cef has beneficial effects on Alzheimer's disease. In the current investigation, the effect of Cef in a mice model of aging was investigated. MATERIALS AND METHODS: Forty male mice were equally aliquoted into four groups as follows: Control (as healthy normal animals), D-galactose (DG) group (treated with 500 mg/kg/day DG for 6 weeks), DG + Cef group (treated with DG plus Cef 200 mg/kg/day for 6 weeks), and Cef group (treated with Cef 200 mg/kg/day for 6 weeks). A battery of behavioral tests was done to evaluate age-related neurocognitive changes. The activities of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), as well as the level of malondialdehyde (MDA) in the brain, were measured by biochemical methods. Also, to determine the brain damage, histopathological alterations in the hippocampus were measured using hematoxylin and eosin (H&E) staining. RESULTS: Our results indicate that neurobehavioral dysfunctions of DG can be prevented by co-administration of Cef. We also found that Cef increases the activity of SOD, GPx, and CAT as well as decreasing the level of MDA in the brain of aged mice. CONCLUSION: Based on our findings, Cef declines neurocognitive dysfunctions in the DG-induced model of aging, possibly through its antioxidative properties.

Effective Treatments for Bladder Cancer Affecting CXCL9/CXCL10/CXCL11/CXCR3 Axis: A Review.

Bladder cancer (BC) originates mainly from the epithelial compartment of the bladder, which is defined as transitional cell carcinoma or urothelial cell carcinoma. About 70% of patients with BC will survive five years from diagnosis. Previous studies revealed that the immune system and its mediators, particularly chemokines, play a crucial role in modulating responses against BC. Chemokines, which serve as chemoattractants for leukocytes, are small proteins that can initiate inflammatory and anti-inflammatory immune responses and also are associated with many aspects of both regulation and progression of mentioned responses. Additionally, these immune mediators can interfere with the other tumor-related processes, including tumor proliferation, neovascularization, and metastases. Among these chemokines, CXC chemokines, including CXCL9, CXCL10, and CXCL11, are recognized as the main ligands of C-X-C motif chemokine receptor 3 (CXCR3) and contribute to related immune responses after therapeutic strategies for BC. Evidence suggests that the production of these chemokines can have two important implications. First, these mediators can trigger the accumulation of CD8+ T cells that can contribute to the elimination of the tumor. Secondly, the production of these chemokines by tumor tissue may trigger the migration and activation of immune cells including myeloid-derived suppressor cells and regulatory T cells, which act in favor of the tumor and its progress. Therefore, in this review, we describe the latest therapeutic approaches based on targeting this axis's components and subsequent immune phenomenon.

Ameliorating effect of troxerutin in unilateral ureteral obstruction induced renal oxidative stress, inflammation, and apoptosis in male rats.

Unilateral ureteral obstruction (UUO) induces renal injury and troxerutin attenuates the inflammatory parameters and decreases oxidative stress. Accordingly, this study explored the renoprotective effect of troxerutin in UUO-induced renal oxidative stress, inflammation, and apoptosis in male Wistar rats. Animals were randomly separated into five groups (n = 8): control, UUO, and three UUO groups treated with troxerutin (1, 10, and 100 mg/kg). UUO-induced and vehicle/troxerutin administration was continued for 3 days. Then serum creatinine, mean arterial pressure (MAP), renal perfusion pressure (RPP), renal vascular resistance (RVR), and renal blood flow (RBF) were measured. Superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase activities, total antioxidant capacity (TAC), and malondialdehyde (MDA) levels as some oxidative stress parameters were measured in the left kidney. The immunoblotting method was applied to evaluate the cleaved caspase-3 Bax, Bcl-2, and TNF-α proteins level. The hematoxylin and eosin method was used to assess the kidney tissue damage score (KTDS). In 3 days, UUO significantly increased serum creatinine level, KTDS, RVR, MDA, Bax, cleaved caspase-3, and TNF-α protein levels (p < 0.05); and decreased RBF, TAC, SOD, catalase, GPx activity levels and Bcl-2 protein expression level in the left kidney (p < 0.05). Troxerutin (100 mg/kg) significantly attenuates the indicators alteration induced by UUO. Our findings represented that the renoprotective effect of troxerutin may be related to its anti-oxidative stress, anti-inflammation, anti-apoptosis, and RBF improver properties.