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As the conventional therapeutic approaches were not completely successful in the treatment of colon cancer, there is still a need for finding the most efficient therapeutic agents. Here we investigated the anticancer activity of HPRP-A1 that was derived from the N-terminal region of Helicobacter pylori ribosomal protein L1 (RpL1) alone or in combination with tumor-homing peptide iRGD and 5-Fluorouracil (5FU) on colon cancer cell lines (CT26 and HT29) and isograft models of colon cancer. We assessed the tumor growth inhibitory activity of HPRP-A1 with or without iRGD and 5FU on colon cancer in vitro and in vivo. In the in vitro part, we investigate the effect of HPRP-A1 alone and in combination with iRGD/5FU. Our results demonstrated that co-administration of HPRP-A1 with iRGD increased the apoptosis, while these two peptides in combination with 5FU increased the intracellular level of p53 that upregulate the pro-apoptotic gene BAX and downregulate the anti-apoptotic gene BCL2. HPRP-A1 blocks the cell cycle progression in G0/G1. Co-administration of two peptides significantly reduced the size and weight of the tumors, while the group that received 5FU in combination with the peptides increased the necrotic and decrease the fibrotic area significantly in the tumor tissues, which also disrupt the oxidant/antioxidant balance. Our results indicated that HPRP-A1 could be considered an effective agent toward colon cancer in vitro and in vivo with the ability to enhance the effects of conventional chemotherapy agent 5FU.

Background: There are controversial results available about using angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) and the development of cancers or improvement of clinical outcomes. Studies reported that using ACEI/ARB may enhance the development of hepatocellular carcinoma (HCC) and clinical outcomes. Objective: This meta-analysis aimed to assess the relationship between ACEI/ARB therapy and the development of HCC. Methods: PubMed, EMBASE and the Cochrane library were reviewed to identify clinical studies investigating the association between ACEI/ARB therapy and the risk of HCC development. The pooled risk ratio (RR) with 95% confidence intervals collected for the association between using ACEIs/ARBs and HCC development. Results: Patients with HCC benefit from the treatment with both ACEIs and ARBs (RR 0.704, 95% CI 0.526- 0.944, p = 0.019). However, only using ARBs was related to HCC risk (0.545 95% CI 0.470-0.632, P Conclusion: Despite the small number and heterogeneity of the studies evaluating the relationship between treatment with ARBs and ACEIs and the development of HCC, our meta-analysis demonstrates that they may reduce the risk of HCC.

Background: Epileptic seizures affect the life of noticeable number of people in all over the world. Tanacetum parthenium (TP) is used in traditional medicine. We studied the effects of hydro- ethanolic extract of TP and its n-butanol and aqueous fractions on brain oxidative damage in pentylenetetrazole (PTZ)-induced seizures in mice. Methods: Male mice were divided into: (1) Control; (2) PTZ (100 mg/kg, i.p.); (3-5) hydro-ethanolic extract of TP (50, 100 and 200 mg/kg); (6) n-butanol (NBut) (100 mg/kg) and (7) aqueous (Aq) (100 mg/kg) fractions. Extracts were injected (i.p.) for 3 days and 30 min before PTZ. Latencies in onset of Minimal Clonic Seizures (MCS) and Generalized Tonic-Clonic Seizures (GTCS) as well as biochemical indicators were evaluated. Results: Medium dose of TP extract and NBut fraction prolonged the MSC and GTCS latencies. Biochemical data confirmed that administration of hydro-ethanolic extract of TP significantly reduced MDA and enhanced total thiol content and the activity of SOD and CAT in brain tissues. Comparison the effect of NBut and Aq fractions with medium dose indicated a higher level of MDA and lower amount of total thiol content and the activity of SOD and CAT in brain tissues of PTZ-Aq100 and PTZ-NBut100 groups than PTZ-TP100 group. Conclusion: Results demonstrated that the medium dose of TP extract had the most protective effect against brain oxidative damage in PTZ-induced seizure model. N-butanol and aqueous fractions of TP could not exert stronger effect than medium dose on reduction PTZ-induced brain oxidative stress. Results: Medium dose of TP extract and NBut fraction prolonged the MSC and GTCS latencies. Biochemical data confirmed that administration of hydro-ethanolic extract of TP significantly reduced MDA and enhanced total thiol content and the activity of SOD and CAT in brain tissues. Comparison the effect of NBut and Aq fractions with medium dose indicated a higher level of MDA and lower amount of total thiol content and the activity of SOD and CAT in brain tissues of PTZ-Aq100 and PTZ-NBut100 groups than PTZ-TP100 group. Conclusion: Results demonstrated that the medium dose of TP extract had the most protective effect against brain oxidative damage in PTZ-induced seizure model. N-butanol and aqueous fractions of TP could not exert stronger effect than medium dose on reduction PTZ-induced brain oxidative stress.

Background\ud Angiotensin II receptor blockers (ARBs) have a potential role in reducing inflammation and fibrosis. We have integrated systems and molecular biology approaches to investigate the therapeutic potential of ARBs in preventing postsurgical adhesion band formation.\ud \ud Material and methods\ud we have followed the ARRIVE guidelines point by point during experimental studies. Telmisartan (1 and 9 mg/kg), valsartan (1 and 9 mg/kg), and losartan (1 and 10 mg/kg) were administered intraperitoneally in different groups of male albino Wistar rat. After 7 d of treatment, macroscopic evidence and score of fibrotic bands based on scaling methods was performed. Moreover, the anti-inflammatory and antifibrosis effects of telmisartan on reduction of fibrotic bands were investigated by using histopathology, ELISA, and real-time polymerase chain reaction methods.\ud \ud Results\ud Telmisartan, but not losartan or valsartan, prevented the frequency as well as the stability of adhesion bands. Telmisartan appears to elicit anti-inflammatory responses by attenuating submucosal edema, suppressing proinflammatory cytokines, decreasing proinflammatory cell infiltration, and inhibiting oxidative stress at the site of peritoneal surgery. We also showed that telmisartan prevents fibrotic adhesion band formation by reducing excessive collagen deposition and suppression of profibrotic genes expression at the peritoneum adhesion tissues.\ud \ud Conclusions\ud These results support the potential application of telmisartan in preventing postsurgical adhesion band formation by inhibiting key pathologic responses of inflammation and fibrosis in postsurgery patients.

Background: Frequent seizure is followed by overproduction of free radicals and brain oxidative stress. Renin angiotensin system (RAS) has some effects on central nervous system. We designed this research to challenge the effect of captopril as an angiotensin converting enzyme (ACE) inhibitor against brain oxidative stress in pentylenetetrazole (PTZ) -induced seizures in mice. Methods: The groups were including (1) Control (saline); (2) PTZ (100 mg/kg, i.p.), (3-5) PTZ- captopril (Capto) that received three doses of Capto 10, 50 and 100 mg/kg 30 min before PTZ injection. Latency time in the onset minimal clonic seizures (MCS) and generalized tonic-clonic seizures (GTCS) were recorded. The level of malondialdehyde (MDA) and total thiol, as well as superoxide dismutase (SOD) and catalase (CAT) activity in the hippocampus and cortex were measured. Results: All doses of captopril postponed the onset of MCS and GTCS. Accumulation of MDA in the brain tissues of PTZ group was higher than control group, while total thiol content and CAT activity were lower. Pretreatment with captopril (100 mg/kg) diminished MDA concentration compared with PTZ group. Captopril (50 and 100 mg/kg) also increased the level of total thiol groups versus PTZ group. Captopril injection (50 and 100 mg/kg) elevated the activity of SOD and CAT in the brain tissues. In addition captopril administration diminished mortality rate caused by PTZ. Conclusion: Findings demonstrated that convulsions caused by PTZ were followed by oxidative stress status in the brain tissues. Pretreatment with captopril attenuated the effect of PTZ on brain tissue oxidative damage.

Here, we have investigated the therapeutic potency of EW-7197, a transforming growth factor-β type I receptor kinase inhibitor, against postsurgical adhesion band formation. Our results showed that this pharmacological inhibitor prevented the frequency and the stability of adhesion bands in mice model. We have also shown that downregulation of proinflammatory cytokines, reduce submucosal edema, attenuation of proinflammatory cell infiltration, inhibition of oxidative stress, decrease in excessive collagen deposition, and suppression of profibrotic genes at the site of surgery are some of the mechanisms by which EW-7197 elicits its protective responses against adhesion band formation. These results clearly suggest that EW-7197 has novel therapeutic properties against postsurgical adhesion band formation with clinically translational potential of inhibiting key pathological responses of inflammation and fibrosis in postsurgery patients.

Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that may play an important role in the evolution of cancers, due to their effects on cancer cell metabolism. Statins affect several potential pathways, including cell proliferation, angiogenesis, apoptosis and metastasis. The number of trials assessing the putative clinical benefits of statins in cancer is increasing. Currently, there are several trials listed on the global trial identifier website clinicaltrials.gov. Given the compelling evidence from these trials in a variety of clinical settings, there have been calls for a clinical trial of statins in the adjuvant gastrointestinal cancer setting. However, randomized controlled trials on specific cancer types in relation to statin use, as well as studies on populations without a clinical indication for using statins, have elucidated some potential underlying biological mechanisms, and the investigation of different statins is probably warranted. It would be useful for these trials to incorporate the assessment of tumour biomarkers predictive of statin response in their design. This review summarizes the recent preclinical and clinical studies that assess the application of statins in the treatment of gastrointestinal cancers with particular emphasize on their association with cancer risk.

Colorectal cancer is one of the most common cancers globally. A large portion of colorectal cancer patients who are treated with conventional chemotherapy eventually develop local recurrence or metastases. The failure of a complete cure in colorectal cancer patients may be related to the lack of complete eradication of cancer stem cells when using conventional therapy. Colorectal cancer stem cells comprise a small population of tumor cells that possess the properties of rapid proliferation and differentiation. The colorectal cancer stem cells are also phenotypically and molecularly distinct, and resistant to conventional chemo-radiotherapy. Therefore, it is important to identify approaches in combination with conventional therapy for targeting and eradicating cancer cells. The aim of this review was to summarize the main findings of recent studies on targeting colorectal cancer stem cells as a novel therapeutic approach in colorectal cancer treatment.

Background The therapeutic potency of Rigosertib (RGS) in the treatment of the myelodysplastic syndrome has been investigated previously, but little is known about its mechanisms of action. Methods The present study integrates systems and molecular biology approaches to investigate the mechanisms of the anti-tumor effects of RGS, either alone or in combination with 5-FU in cellular and animal models of colorectal cancer (CRC). Results The effects of RGS were more pronounced in dedifferentiated CRC cell types, compared to cell types that were epithelial-like. RGS inhibited cell proliferation and cell cycle progression in a cell-type specific manner, and that was dependent on the presence of mutations in KRAS, or its down-stream effectors. RGS increased both early and late apoptosis, by regulating the expression of p53, BAX and MDM2 in tumor model. We also found that RGS induced cell senescence in tumor tissues by increasing ROS generation, and impairing oxidant/anti-oxidant balance. RGS also inhibited angiogenesis and metastatic behavior of CRC cells, by regulating the expression of CD31, E-cadherin, and matrix metalloproteinases-2 and 9. Conclusion Our findings support the therapeutic potential of this potent RAS signaling inhibitor either alone or in combination with standard regimens for the management of patients with CRC.

Background: Blood-brain barrier (BBB), as well-known protection for the brain, plays an active role in normal homeostasis. It might be changed by a range of inflammatory mediators to have a role in sickness behaviors. Objectives: Regarding the anti-inflammatory effects of thymoquinone (TQ), its protection against BBB permeability, as a possible mechanism for protective effects against sickness behaviors elicited by lipopolysaccharide (LPS), was evaluated in rats. Methods: The animals were grouped as follows and treated (n = 10 in each): (1) control (saline); (2) LPS 1 mg/kg, was injected two hours before behavioral tests for two weeks; (3-5) 2, 5, and 10 mg/kg TQ, respectively was injected 30 min before LPS injection. Open-field (OF), elevated plus-maze (EPM) and Forced Swimming test (FST) were done. Finally, the animals were anesthetized to evaluate for BBB permeability using Evans blue (EB) dye method. Results: Compared with control, LPS decreased the peripheral distance and crossing and also total crossing and distance in OF, (P < 0.01 - P < 0.001). The central crossing and distance and central time in all three treatment groups were more than LPS (P < 0.05 - P < 0.001). LPS also reduced the entries and the time spent in the open arm while increased the time spent in the closed arm in EPM (P < 0.05 - P < 0.001). The effects of LPS were reversed by TQ (P < 0.05 - P < 0.001). In FST, the immobility time and active time were increased and decreased by LPS compared with control (P < 0.001), respectively. In all three TQ-treated groups, the active and climbing times were more while the immobility time was fewer than the LPS (P < 0.05 - P < 0.001). The animals of the LPS group showed more EB dye content in their brain tissue than the control group (P < 0.05 - P < 0.001). TQ significantly reduced EB dye content of the brain tissues (P < 0.05 - P < 0.001). Conclusions: According to this study, protection against BBB permeability as a possible mechanism for the protective effects of TQ against sickness behaviors induced by LPS might be suggested.

Circulating inflammatory factor inorganic polyphosphate (polyP) released from activated platelets could enhance factor XII and bradykinin resulted in increased capillary leakage and vascular permeability. PolyP induce inflammatory responses through mTOR pathway in endothelial cells, which is being reported in several diseases including atherosclerosis, thrombosis, sepsis, and cancer. Systems and molecular biology approaches were used to explore the regulatory role of the AMPK activator, metformin, on polyP-induced hyper-permeability in different organs in three different models of polyP-induced hyper-permeability including local, systemic shortand systemic long-term approaches in murine models. Our results showed that polyP disrupts endothelial barrier integrity in skin, liver, kidney, brain, heart, and lung in all three study models and metformin abrogates the disruptive effect of polyP. We also showed that activation of AMPK signaling pathway, regulation of oxidant/ anti-oxidant balance, as well as decrease in inflammatory cell infiltration constitute a set of molecular mechanisms through which metformin elicits it's protective responses against polyP-induced hyper-permeability. These results support the clinical values of AMPK activators including the FDA-approved metformin in attenuating vascular damage in polyP-associated inflammatory diseases.

Background Isoniazid (INH) is well known as a first-line anti-tuberculosis, while some studies demonstrate that it has anti-inflammatory activity via a different mechanism such as inhibition the production of IL-1, ROS, activation of PPARγ expression, inhibition of the transcriptional regulatory activity of NF-κB and AP-1. The aim of this study, investigate the anti-inflammatory effect of INH and INH combined with Sulfasalazine-loaded nanoparticles (NPs) in the ulcerative colitis mouse model. Methods To investigate the anti-inflammatory effect of INH and NPs in the ulcerative colitis mice model, we evaluated the effect of INH clinical symptoms and colonic mucosal histology in colitis. Result The present study demonstrates that combination therapy of INH with sulfasalazine as well as NPs reduces the symptom of ulcerative colitis and improved disease activity index include body lose weight, diarrhea, rectal bleeding, colonic length, spleen weight, and colon histopathological score in DSS-induced colitis mice model. Conclusion Our results suggest that the nanoforms of INH with sulfasalazine enhances the therapeutic effect of the drugs in the treatment of ulcerative colitis.

Background Cerium (IV) oxide (CeO2) exhibit anti-inflammatory activity via scavenge free radicals and decreasing the oxygen species (ROS) production. Here we aimed to exhibit the therapeutic effect of this nanoparticle in experimental colitis models. Methods Cerium oxide nanoparticles (CeONPs) were synthesized via using UiO-66 as a precursor. We used dextran sodium sulfate (DSS) to induce colitis in experimental models to investigate the anti-inflammatory effect of CeONPs. Colitis models are divided into four groups to receive the treatment, including control, colitis, cerium oxide, and sulfasalazine. We evaluated the therapeutic effects of CeONPs for the increased colitis clinical symptoms and attenuated the histological damage to colon tissue in colitis. Result This nanoparticle was significantly able to reduce the clinical symptoms of colitis. Moreover, CeONPs can enhance the disease activity index such as body lose weight, diarrhea, rectal bleeding, colon length, and spleen weight. Moreover, CeONPs showed a significant reduction in the histological characteristics of the colitis models. Conclusion These results suggest that CeONPs can be considered as promising therapeutic agents in treating the ulcerative colitis.

Aims: Rigosertib (RGS) is a PI3K inhibitor that exerts protective effects against tumor progression and cancer-related inflammation. This study was aimed to explore the regulatory effects of RGS on proliferative, pro-fibrotic and inflammatory factors in DSS- induced colitis mice model. Materials and methods: The present study integrates systems and molecular biology approaches to investigate the therapeutic potency of RGS in an experimental model of colitis specifically examining its effects on the PI3K/AKT and NF-kappa B signaling pathways. Key findings: Analysis of time-resolved proteome profiling showed that PI3K-AKT inhibitors regulate expression of many proteins in all stages of inflammation, fibrogenesis and extracellular matrix remodeling. Consistent with our in-silico findings, RGS improved colitis disease activity as assessed by changes in body weight, degree of stool consistency, rectal bleeding and prolapse. RGS also reduced oxidative stress markers and colon histopathological score by decreasing inflammatory responses in colon tissues. Moreover, expression of pro-fibrotic and pro-inflammatory factors including Acta 2, Col 1a1, Col 1a2, IL-1 beta, TNF-alpha, INF-gamma, and MCP-1 were suppressed in the mice treated with RGS compared to the control group. The protective effects of RGS were mediated by inactivation of PI3K/AKT and NF-kB signaling pathways. Significance: This study clearly demonstrates the anti-proliferative, anti-inflammatory and anti-fibrotic effects of RGS in colitis that may have implications for the treatment of colitis and colitis-associated cancer.

Objectives: Thymoquinone (TQ) is one of the active ingredients of herbal plants such as Nigella sativa L. (NS) which has beneficial effects on the body. The beneficial effects of TQ on the cardiovascular system have reported. This study aimed to investigate the effect of TQ on cardiac fibrosis and permeability, serum and tissue concentration of inflammatory markers and oxidative stress status in chronic lipopolysaccharide exposure in male rats. Methods: Seventy male Wistar rats were randomly divided into five groups as follows: (1) control; (2) LPS (1 mg/kg/day); (3-5) LPS + TQ with three doses of 2, 5 and 10 mg/kg (n=14 in each group). After 3 weeks, serum and cardiac levels of IL-1β, TNF-α and nitric oxide (NO) metabolites, and cardiac levels of malondialdehyde (MDA), total thiol groups, catalase (CAT) and superoxide dismutase (SOD) activities, permeability of heart tissue (evaluated by Evans blue dye method) and myocardial fibrosis were determined, histologically. Results: LPS administration induced myocardial and perivascular fibrosis and increased cardiac oxidative stress (MDA), inflammatory markers and heart permeability, while, reduced anti-oxidative enzymes (SOD and CAT) and the total thiol group. Administration of TQ significantly attenuated these observations. Conclusion: TQ improved myocardial and perivascular fibrosis through suppression of chronic inflammation and improving oxidative stress status and can be considered for attenuation of cardiac fibrosis in conditions with chronic low-grade inflammation.

EW-7197 is a transforming growth factor-β type I receptor kinase inhibitor with potential anti-inflammatory and antifibrotic properties. Here, we investigate the potential therapeutic effects of EW-7197 in a murine model of ulcerative colitis. EW-7197 attenuated the colitis disease activity index by improving rectal bleeding, body weight, and degree of stool consistency. EW-7197 also reduced colorectal tissue damage and the colon histopathological score by reducing crypt loss, mucosal damage, and tissue inflammation. Moreover, EW-7197 appeared to ameliorate the inflammatory and fibrotic responses by reducing oxidative stress, reducing submucosal edema and inflammatory cell infiltration, downregulating proinflammatory and pro-fibrotic genes, and inhibiting excessive collagen deposition in inflamed and fibrotic ulcerative colitis tissues. These results suggest that EW-7197 has potentially useful therapeutic properties against colitis, with clinically translational potential of inhibiting key pathological responses of inflammation and fibrosis in patients with colitis.

Objective The study objective was to determine the protective effects of thymoquinone (TQ) on brain tissues oxidative stress status, hippocampal cytokine level, and learning and memory deficits induced by lipopolysaccharide (LPS) in rats. Methods Animals were randomly divided into the following groups and treated: (1) Control (saline), (2) LPS (1 mg/kg i.p.), (3–5) 2, 5 or 10 mg/kg TQ extract 30 min before LPS injection. The treatment was started since two weeks before the behavioral experiments and continued during the behavioral tests (LPS injected 2 h before each behavioral experiment). Finally, the brains were removed for biochemical assessments. Results Morris water maze (MWM) test results showed that LPS increased escape latency compared to control group whereas TQ decreased them vs. LPS group. In passive avoidance (PA) test, LPS reduced the latency to enter the dark compartment vs. control group, while TQ treatment attenuated this effect of LPS. Additionally, LPS increased interleukin-6 (IL-6) and tumor necrosis alpha (TNF-α) in the hippocampal tissues. It also elevated malondialdehyde (MDA) and nitric oxide (NO) metabolites and decreased thiol content, superoxide dismutase (SOD) and catalase (CAT) in both hippocampus and cortex vs. control group, while TQ decreased IL-6, TNF-α, MDA and NO metabolites and increased thiol content, SOD and CAT compared to LPS group. Conclusion Findings of current study indicated that TQ improved LPS-induced learning and memory impairments induced by LPS in rats by attenuating the hippocampal cytokine levels and brain tissues oxidative damage.

Oxaliplatin is being used in different malignancies and several side effects are reported for patients taking Oxaliplatin, including peripheral neuropathy, nausea and vomiting, diarrhea, mouth sores, low blood counts, fatigue, loss of appetite, etc. Here we have developed a targeted anticancer drug delivery system based on folate-conjugated amine-functionalized UiO-66 for the delivery of oxaliplatin (OX). UiO-66-NH2 (U) and UiO-66-NH2–FA(FU) were pre-functionalized by the incorporation of folic acid (FA) into the structure via coordination of the carboxylate group of FA. The FTIR spectra of drug-loaded U and FU showed the presence of new carboxylic and aliphatic groups of OX and FA. Powder X-ray diffraction (PXRD) patterns were matched accordingly with the reference pattern and FESEM results showed semi-spherical particles (115–128 nm). The evaluated amounts of OX in U and FU were calculated 304.5 and 293 mg/g, respectively. The initial burst release of OX was 15.7% per hour for U(OX) and 10.8% per hour for FU(OX). The final release plateau gives 62.9% and 52.3% for U(OX) and FU(OX). To evaluate the application of the prepared delivery platform, they were tested on colorectal cancer cells (CT-26) via MTT assay, cell migration assay, and spheroid model. IC50 values obtained from MTT assay were 21.38, 95.50, and 18.20 μg/mL for OX, U(OX), and FU(OX), respectively. After three days of treatment, the CT26 spheroids at two doses of 500 and 50 μg/mL of U(OX) and FU(OX) showed volume reduction. Moreover, the oxidative behavior of the prepared systems within the cell was assessed by total thiol, malondialdehyde, and superoxide dismutase activity. The results showed that FU(OX) had higher efficacy in preventing the growth of CT-26 spheroid, and was more effective than oxaliplation in cell migration inhibition, and induced higher oxidative stress and apoptosis.

Nigella sativa (NS) (Ranunculaceae) used as a protective and therapeutic traditional medicine. This study evaluates the effect of NS on inflammation-induced myocardial fibrosis, serum and tissue inflammatory markers, and oxidative stress status in male rats. Fifty male Wistar rats were divided into five groups: (1) control; (2) lipopolysaccharide (LPS), 1 mg/kg/day; (3) LPS + NS (hydroalcoholic extract), 100 mg/kg/day; (4) LPS + NS, 200 mg/kg/day; (5) LPS + NS, 400 mg/kg/day (n = 10 in each group). The duration of LPS administration was two weeks. At the end of the experiment, blood samples were taken and ventricles were homogenized and stained for histological evaluation. Serum nitrite levels were lower in LPS group than the control group (22.98 ± 1.03 vs 28.5 ± 0.93 μmol/L), in which they were significantly increased by NS treatment (P < 0.05). Higher levels of heart interlukine-6 (IL-6) and tumor necrosis factor-α (TNF-α) were observed in LPS group compared to the controls (IL-6: 6805 ± 656 vs 4733 ± 691 pg/mL; TNF-α: 6504 ± 501 vs 5309 ± 452 pg/mL), in which they were reduced by NS 400 mg/kg compared to LPS groups (P < 0.05). A significant increment of malondialdehyde and reduction in heart total thiol, superoxide dismutase and catalase concentrations were observed in LPS group (p < 0.05) which significantly restored with treatment by three doses of NS. Histopathological studies showed higher inflammatory cell infiltrates, cardiac fibrosis, and collagen deposition in LPS group, which were reduced by the administration of NS. Treatment by NS reduced myocardial fibrosis in inflammation-induced fibrosis, possibly through improving oxidative/anti-oxidative balance.

Aims Ulcerative colitis (UC) is an inflammatory disease with a high incidence globally. The conventional treatment for UC includes sulfasalazine, used to control the pathogenic complication of the inflammatory and immune responses, although this is not very effective. To overcome the side effects and improve the therapeutic outcomes, novel therapeutic agents are warranted. Silver nanoparticles have been found to have potent therapeutic and anti-inflammatory properties in the management of inflammatory diseases. Methods The therapeutic potency of silver nanoparticles containing sulfasalazine (SSZ-AgNPs) was investigated by assessing a pathological score, histological staining and real time PCR methods in DSS- induced colitis in a murine model. Results SSZ-AgNPs was found to improve the disease activity index, colon shortening and body weight loss. SSZ-AgNPs was also found to reduce histopathological evidence of injury, by reducing inflammatory responses in colonic tissues. Additionally, treatment with SSZ-AgNPs resulted in downregulation of pro-fibrotic and pro-inflammatory factors such as: Col 1a1, Col 1a2, TNF-α, and INF-γ. Conclusion In our preclinical study we found evidence for the anti-inflammatory and anti-fibrotic activity of SSZ-AgNPs as a potential therapeutic agent, and further investigations in clinical studies are warranted.

Colorectal cancer (CRC) is one of the most common causes of cancer-related death in the world. There is a document that angiotensin (AT) which is found to be involved in the progression of CRC. Furthermore, Angiotensin receptor inhibitors (ARIs) and angiotensin-converting enzyme Inhibitors (ACE-Is) demonstrate activity in CRC by their inhibition of both Insulin-like growth factor 1 (IGF-1) and Vascular endothelial growth factor (VEGF), and therefore present a potentially novel therapeutic strategy in colorectal cancer, which have summarized in the current review. Preclinical studies have illustrated the direct effect of major active mediator angiotensin II (ATII) on the promotion of angiogenesis through VEGF and other proliferative mediators. Suppression of the angiotensin II type I receptor (AT1R) via ACE-Is has shown a reduction in the development of solid tumor and metastasis, particularly CRC incidence, polyp formation, and distant metastasis. MicroRNAs (miRs) are a family of small nucleotides without coding that plays an important role after transcribing hundreds to thousands of non-coding and coding gene. Against this background, the application of anti-hypertensive medications such as losartan might have a therapeutic impact, although further preclinical and clinical studies might provide novel insight into the potentially beneficial effect of ACE-Is in the treatment of colorectal cancer patients.

Thymoquinone (TQ) is the main active ingredient of Nigella sativa seeds with various pharmacological effects. The aim of this study was to investigate the effect of TQ on renal fibrosis and permeability and oxidative stress status in lipopolysaccharide (LPS)-induced inflammation in male rats. Eighty male Wistar rats were divided into 5 groups as follow: control (received normal saline), LPS (1 mg/kg/day), and LPS+TQ (by doses of 2, 5 and 10 mg/kg/day). After three weeks, the biochemical parameters such as blood urea nitrogen (BUN) and creatinine in serum samples, oxidative stress markers including malondialdehyde (MDA), total thiol groups, superoxide dismutase (SOD) and catalase (CAT) activities in renal tissue homogenate and renal permeability (evaluated by Evan's blue dye method) were measured and renal fibrosis was evaluated, histologically using Masson's trichrome staining. LPS administration induced renal fibrosis (1.49 ± 0.08 vs. 7.15 ± 0.18%) and significantly increased renal permeability (6.03 ± 1.05 vs. 13.5 ± 1.04 μg evans blue(EB)/g tissue), serum BUN and creatinine levels and oxidative stress marker (MDA) (P < 0.05), while, it reduced anti-oxidative markers including total thiol group, SOD and CAT activities (P < 0.05). Administration of TQ significantly improved these alterations which were dose-dependent in oxidative stress markers, renal permeability (TQ 2, 5 and 10 mg/kg: 10.7 ± 0.3, 9.2 ± 1.4 and 11.5 ± 0.6 μg EB/g tissue; respectively) and fibrosis (TQ 2, 5 and 10 mg/kg: 6.09 ± 0.7, 4.26 ± 0.14 and 2.52 ± 0.08%; respectively). In conclusion, administration of TQ reduced renal fibrosis and permeability and improved oxidative stress status. Thus, TQ can be considered in conditions accompanied with chronic inflammation at least as a part of treatment strategy.

Background: Renin-angiotensin (Ang)-aldosterone system not only plays a key role in the regulation of circulatory homeostasis, but also it acts as a powerful pro-inflammatory mediator. The aim of this study was to evaluate the effect of captopril (Cap), a known Ang-converting enzyme inhibitor, on inflammation-induced cardiac fibrosis, and heart oxidative stress status in lipopolysaccharide (LPS)-induced inflammation in male rats. Methods: Fifty male rats were randomly divided into five groups control, LPS (1 mg/kg/day), LPS + Cap 10 mg/kg, LPS + Cap 50 mg/kg and LPS + Cap 100 mg/kg. After 2 weeks, blood samples were taken, and hearts were harvested for evaluation of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and nitric oxide metabolite in serum and tissue hemogenate, histopathology (hematoxylin and eosin and Masson's trichrome) and oxidative stress status. Results: Serum IL-6 and TNF-α concentration were higher in LPS group compared to control and Cap reduced them, significantly. Heart TNF-α and IL-6 contents in LPS group were significantly higher than control (P < 0.05). The administration of Cap significantly decreased inflammatory markers level to control (P < 0.05). The higher levels of malondialdehyde and lower antioxidative markers (total thiol, superoxide dismutase, and catalase) in the heart were observed in LPS group and treatment by Cap improved them, dose-dependently. Histopathological study revealed cardiac fibrosis and more collagen content in LPS group which significantly improved by Cap treatment. Conclusions: Treatment by Cap reduced cardiac fibrosis possibly through improving oxidative stress status, and it can be considered to increase cardiac compliance in this condition.