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Background: Peritoneal adhesions (PA) are a common complication of abdominal operations. Previous studies indicate that inhibition of inflammation and fibrosis at sites of peritoneal damage may prevent the development of intra-abdominal adhesions. Zingiber officinalis Roscoe (ginger) and Panax ginseng (P. ginseng) are herbal products with antioxidant and anti-inflammatory effects that can have restorative properties. Objective: This research aimed to examine the impact of ginger and p. ginseng on prevention of PA in a rat model after surgery. Methods: Following a laparotomy, the wall of the cecum was rubbed to induce intra-abdominal adherence in Wistar rats. Ginger (400mg/kg) and P. ginseng (500mg/kg) were orally adminstered to the animals. The animals were sacrificed on the 10th day after surgery, and the Nair and Leach scoring system was used to assess adhesion. The microscopic histology of the induced cecal adhesions was evaluated. An enzyme-linked immunosorbent assay (ELISA) was used to determined tissue levels of transforming growth factor-beta (TGF-β) on homogenized PA tissue. Real-time PCR was performed to quantify the mRNA expression of IL-1β, TNF-α, Col 1a1, and Col 3a1 in rat tissue. Result: The adhesion score and histopathological rating based on the Nair and Leach scoring criteria showed lower adhesion scores in the group of rats treated with P. ginseng compared to the control group (p Conclusion: The study's outcome recommends that P. ginseng could be an effective agent for preventing the PA and inflammation during the post-operative stage.

In this study we investigated the therapeutic potential of angiotensin II pathway inhibitors in attenuating post-surgical adhesion band formation in tendon injury.We assigned 30 Wistar albino rats to 5 groups, including negative control, positive control, sham, Telmisartan- and Enalapril-treated groups (n=6). Telmisartan and Enalapril at a dose of 10 mg/kg were administered intraperitoneally for 21 days. Hematoxylin-Eosin, and Masson's trichrome staining were used to measure the inflammatory cell accumulation and collagen deposition in the Achilles tendon tissue sections. Oxidative stress markers were analyzed in tissue samples by spectrophotometric methods. Properties of Achilles tendon adhesions were compared based on Tang and Ishiyama scoring systems in the presence and absence of angiotensin II pathway inhibitors.Telmisartan and Enalapril reduced severity, length, and density of surgical-induced tendon adhesion at site of injury (***p0.001). Our results showed that administration of angiotensin II pathway inhibitors decreased infiltration of inflammatory cells to the injured area (*p0.05) and suppressed inflammation by regulating oxidative stress markers including MDA (***p0.001), total thiol (***p0.001), CAT (***p0.001), and SOD (***p0.001), in post-operative Achilles tendon tissues. Significant lower collagen deposition and formation of fibrotic tissues was seen in Telmisartan- and Enalapril-treated groups as detected by Masson's trichrome staining which correlated with a decrease in quantity (**p0.01) and grading of fibrosis score (***p0.001), in adhesive tissues. Moreover, inhibition of angiotensin II pathway could also ameliorate mechanical properties including ultimate load (***p0.001), and ultimate stress (*p0.05) in injured Tendons.Our results showed that ssuppression of inflammation and fibrosis are two mechanisms by which Telmisartan and Enalapril elicit potent protective responses post Achilles tendon injuries.

Abstract: The incidence of colorectal cancer (CRC) has significantly increased in recent decades, which has made this disease an important global health issue. Despite many efforts, there is no useful prognostic or diagnostic biomarker for CRC. Heat shock protein 27 (Hsp27) is one of the most studied members of Hsp family. It has attracted particular attention in CRC pathogenesis, since it is involved in fundamental cell functions for cell survival. Evidence show that Hsp27 plays important roles in CRC progression and metastasis. Hsp27 overexpression has been observed in CRC and suggested to be associated with CRC poor prognosis. In the present review, we focus on the current knowledge on the role of Hsp27 in CRC carcinogenesis and the underlying mechanisms. In addition, we discuss the value of targeting Hsp27 in CRC treatment.

Background: Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are mainly known as anti-hypertensive drugs. Recent evidence suggests their anti-tumor potential against renal cancer. More than one-fourth of patients present with metastasis on their first visit. Objective: The purpose of the current study was to examine the potential clinical impact of ACEI/ARB on metastatic renal cell carcinoma (mRCC). Methods: We searched through several online databases, including Pubmed, Scopus, Web of Science, and Embase, to find clinical studies that have investigated the association between treatment with ACEI/ARB and the survival of patients with mRCC. The hazard ratio (HR) and 95% confidence interval (95% CI) were utilized to assess the strength of the association. Results: A total of 6 studies with a total number of 2,364 patients were found eligible for the final analysis. The HR for the relationship between ACEI/ARB use and overall survival (OS) showed patients undergoing treatment with ACEI/ARB to have higher OS than non-users (HR: 0.664, 95% CI 0.577-0.764, p=0.000). Furthermore, the HR for the relationship between ACEI/ARB use and progression-free survival (PFS) showed patients undergoing treatment with ACEI/ARB to have higher PFS than non-users (HR: 0.734, 95% CI 0.695-0.794, p=0.000). Conclusion: The results of this review offer ACEI/ARB as a potential therapeutic option associated with improved survival outcomes in patients receiving anti-vascular endothelial growth factor therapy.

Abstract: Colorectal cancer (CRC) is the third most common cancer worldwide. Despite the enormous amount of effort in the diagnosis and treatment of CRC, the overall survival rate of patients remains low. The precise molecular and cellular basis underlying CRC has not been completely understood yet. Over time, new genes and molecular pathways involved in the pathogenesis of the disease are being identified. The accurate discovery of these genes and signaling pathways are important and urgent missions for the next generation of anticancer therapy research. Chaperone DnaJ, also known as Hsp40 (heat shock protein 40), has been of particular interest in CRC pathogenesis, as it is involved in the fundamental cell activities for maintaining cellular homeostasis. Evidence shows that protein family members of DnaJ/Hsp40 play both roles, enhancing and reducing the growth of CRC cells. In the present review, we focus on the current knowledge of the molecular mechanisms responsible for DnaJ/Hsp40 in CRC carcinogenesis and biology.

Lung metastasis is the main cause of death in patients with colorectal carcinoma (CRC). Angiotensin II has been confirmed to facilitate cancer cell progression and metastasis. In this study, the possible anti-metastatic effects of an angiotensin II receptor type 1 (AT1R) antagonist, valsartan, have been investigated in an experimental CRC lung metastasis model.An animal CRC lung metastasis model was used, involving intravenous injection of CRC cells. The experimental groups included (1) control group; (2) 5-FU (5-fluorouracil) group (5 mg/kg/every other day; ip); (3) valsartan group (40 mg/kg/day; po); and (4) valsartan + 5-FU group (combination group; valsartan 40 mg/kg/day, oral gavage, and 5-FU 5 mg/kg/every other day; ip). After 11 days, macroscopic and histological evaluations of lung tissues have been done for evaluation of lung metastatic nodules. In addition, inflammatory and angiogenic markers and oxidative stress index were measured in lung tissue.Our results showed that administration of valsartan especially in combination with 5-FU significantly reduced lung metastatic nodule and metastatic area (p 0.05) in macroscopic and histological evaluations stained by hematoxylin-eosin. Measurement of inflammatory, angiogenic, and oxidative/antioxidative markers in lung tissue indicated that the level of IL-6, angiogenic markers (VEGF and VEGFR-1), and antioxidative markers significantly reduced in combination group (p 0.05) while the MDA as a marker of oxidative stress increased (p 0.05).These results suggest that valsartan in combination with standard chemotherapeutic agents can have a synergistic effect in treatment of lung metastasis of CRC.

UiO-66-NH2 (U) and its magnetic UiO-66-NH2 form (MU) were used to enhance Oxaliplatin (OX) efficacy. The fundamental physical and structural properties of nanoparticles were characterized via X-ray Diffraction (XRD), Fourier Transform Infrared (FTIR), UV–Visible (UV–Vis), Brunauer–Emmett–Teller (BET) surface area analysis, field emission scanning electron microscopy (FESEM), Energy-dispersive X-ray analysis (EDAX) and mapping, and Dynamic light scattering (DLS). The results further showed an improved anticancer activity and efficacy of the designed drug delivery systems (DDSs) compared to OX in 2-and 3-dimensional models of colorectal cancer in which cell viability, proliferation and migration, and morphology were assessed. Additionally, the oxidative/antioxidant activity of U and MU-loaded OX demonstrated greater oxidative behavior compared to OX. In vitro experiments showed that U and MU could inhibit the proliferation and migration of colorectal cancer cells in a dose-dependent manner. The half-maximal inhibitory concentration (IC50) values were found to be 6.10 ppm for OX, 18.47 ppm for MU(OX), and 47.02 ppm for U(OX), respectively. The U(OX) and MU(OX) were more effective than OX in terms of drug release. The results indicate that U and MU show considerable promise as a novel and effective drug delivery system for the treatment of colorectal cancer and possibly other malignancies.

Coronavirus disease 2019 (SARS-CoV-2) (COVID-19) has recently raised worldwide public health concerns. The available data on COVID-19 in patients with diabetes is limited but generally indicate that there is an increased risk of developing COVID-19 infection in diabetic patients, which ultimately impacts the overall patient’s survival. Various aspects might be involved; however, the exact mechanisms and interrelationships between diabetes and the novel COVID-19 have not yet been fully elucidated. This review summarizes the possible mechanisms by which present diabetes predispose individuals to COVID-19 infection, modulates the hostviral interactions and increases the risk of mortality. We hope this review can provide beneficial information for further studies and contribute to improved disease management of diabetic patients with COVID-19.

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.

Colorectal cancer (CRC) is one of the most common leading causes of cancer death in the world. Although EGFR inhibitors have established efficacy in metastatic colorectal cancer (mCRC), some patients do not respond to this treatment. The EGFR inhibitors' failure and acquired resistance are partly due to KRAS and BRAF mutations. Thus, prognostic biomarkers that help to select eligible patients are highly in demand. To improve patient selection, assessment of mutational status in circulating cell free DNA (cfDNA), which possibly represents the dynamicity of tumor genetic status better than tumor tissue, could be advantageous. This review summarizes the current knowledge of the prognostic value of cfDNA in patients with mCRC treated with EGFR inhibitors with emphasis on the clinical importance of identification of KRAS and BRAF mutations.

Background In this study we investigated the therapeutic potential of the phytosomal form of pharmacologically active component of Curcuma longa, curcumin, in attenuating Post-operative adhesion bands (PSAB) formation in both peritoneal and peritendinous surgeries in animal models. Methods Bio-mechanical, Histological and quantitative evaluation of inflammation, and total fibrosis scores were graded and measured in the presence and absence of phytosomal curcumin. Results Our results showed that phytosomal curcumin significantly decreased severity, length, density and tolerance of mobility of peritendinous adhesions as well as incidence and severity of abdominal fibrotic bands post-surgery. We showed that curcumin could decrease inflammation by attenuating recruitment of inflammatory cells and regulating oxidant/anti-oxidant balance in post-operative tissue samples. Moreover, markedly lower fibrosis scores were obtained in the adhesive tissues of phytosomal curcumin-treated groups which correlated with a significant decrease in quantity, quality and grading of fibers, and collagen deposition in animal models. Conclusion These results suggest that the anti-inflammatory and anti-fibrotic properties of phytosomal curcumin, has therapeutic potential for preventing PSAB formation.”

Background: Overexpression of the angiotensin-II receptor and renin–angiotensin system (RAS) has been reported in several malignancies, including colorectal-cancer (CRC), indicating its potential value as a therapeutic target. Here we explored the impact of targeting the RAS using an angiotensin II receptor blocker, valsartan, alone and its combination with Fluorouracil (5-FU) in in vitro and in vivo models of CRC. Methods: Anti-proliferative activity of valsartan was evaluated in 2−/3-dimensional in vitro and in vivo CRC mouse models. The anti-migratory effects of this agent was assessed by wound-healing assay, while apoptosis was studied using 4′,6-diamidino-2-phenylindole or DAPI staining, and staining with Annexin-V–fluorescein isothiocyanate with analysis using FACS. Gene-expression was determined at mRNA and protein levels. We further evaluated the anti-inflammatory properties of valsartan by histological analysis and the measurement of oxidative/antioxidant markers. Gelatin zymography was used to measure matrix metalloproteinase-2 and -9 activity (MMP-2 and 9). Results: Valsartan suppressed CRC cell-growth and synergistically enhanced the anti-tumor-activities of 5-FU by induction of apoptosis, BAX, BCL2, P53 and modulation of the cell cycle. Valsartan inhibited the cell migration by perturbation of MMP2/9. Furthermore, valsartan inhibited tumor-growth, and this was more pronounced when using the valsartan/5-FU combination. The plausible mechanism for this is via the induction of ROS and down-regulation of SOD, thiol/catalase as well as VEGF. Valsartan may protect cells against intestinal fibrosis by modulation of pro-fibrotic and pro-inflammatory factors including interleukins and Col1A1 expression. Conclusions: Our findings demonstrated that targeting RAS pathway using Valsartan interferes with cell-proliferation, induces apoptosis, reduces migration and synergistically interacts with 5-FU, supporting further studies on this new therapeutic approach for colorectal cancer.

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.

Ovarian cancer is the fifth most common gynecological cancer in women globally. Conventional chemotherapy is the first therapeutic approach in the treatment of ovarian cancer, but its success is limited by severe side effects, transient response, and the high prevalence of relapse. Curcumin is a natural product found in the rhizome extract of

Abstract: The renin-angiotensin system (RAS) has been reported to have a role in carcinogenesis, and therefore it may be of value as a potential therapeutic target in inhibiting tumor growth. It has been shown that inhibition of RAS via angiotensin I-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor (ARBs) inhibitors may have a protective effect against several malignancies. Here, we provide an overview of the potential value of the RAS pathway and targeting via ACE/ARB inhibitors in pancreatic cancer. Whilst the potential role of RAS as a target for the treatment of pancreatic cancer has been reported, the use of candesartan with gemcitabine failed to improve outcomes in pancreatic cancer. Another study of 1-3 years using ARB was found to reduce the risk of pancreatic cancer. In line with these trials, others have demonstrated that the ARBs in combination with gemcitabine might improve clinical outcomes in patients with advanced pancreatic cancer. Prospective trials are warranted to investigate this hypothesis.

Mebendazole (MBZ) is an efficacious anthelmintic with known anti-inflammatory and fibrinolytic properties. In this study, we aimed to explore the protective effects of this FDA-approved drug against DSS-induced colitis in a murine model either alone or in combination with Sulfasalazine (SSZ), a standard therapy for ulcerative colitis. We found that MBZ significantly improved colitis disease activity index as assessed by changes in body weight, degree of stool consistency, rectal bleeding, and prolapse. We also found that MBZ ameliorated the colon histopathological score by attenuating crypt loss, mucosal damage, and inflammation score in colitis tissues. Similarly, DSS-induced colon shortening, colon weight loss, and increase in spleen weight were all abrogated in the presence of MBZ. Moreover, MBZ decreased inflammation, possibly by reducing oxidative stress markers, suppressing inflammatory cell infiltration, and down-regulation of inflammatory genes in colon tissues. Furthermore, MBZ potently reduced fibrosis by decreasing collagen deposition and down-regulating pro-fibrotic genes including Col 1a1 and Col 1a2 in colitis tissue homogenates. In conclusion, our study showed that this broad-spectrum anthelminthic could be repurposed as a novel therapy for ulcerative colitis without any observed side effects, however, regarding the concerns about the potential toxicity of MBZ in UC patients, future experiments on MBZ therapy in other models of UC is needed to completely address the toxicity concerns.

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 Abdominal adhesions are common and often develop after abdominal surgery. There are currently no useful targeted pharmacotherapies for adhesive disease. Saffron and its active constituents, Crocin and Crocetin, are wildly used in traditional medicine for alleviating the severity of inflammatory or malignant disease. Purpose The aim of this study was to investigate the therapeutic potential of the pharmacological active component of saffron in attenuating the formation of post-operative adhesion bands using different administration methods in a murine model. Material method saffron extract (100 mg/kg), Crocin (100 mg/kg), and Crocetin (100 mg/kg) were administered intraperitoneally and by gavage in various groups of male Wistar rat post-surgery. Also three groups were first treated intra-peritoneally by saffron extract, Crocin, and Crocetin (100 mg/kg) for 10 days and then had surgery. At the end of the experiments, animals sacrificed for biological assessment. Result A hydro-alcoholic extract of saffron and crocin but not crocetin potently reduced the adhesion band frequency in treatment and pre-treatment groups in the mice given intra-peritoneal (i.p) injections. Following the saffron or crocin administration, histological evaluation and quantitative analysis represented less inflammatory cell infiltration and less collagen composition, compared to control group. Moreover, the oxidative stress was significantly reduced in treatment groups. Conclusion These findings suggest that a hydro-alcoholic extract of saffron or its active compound, crocin, is a potentially novel therapeutic strategy for the prevention of adhesions formation and might be used as beneficial anti-inflammatory or anti-fibrosis agents in clinical trials. Taxonomy Abdominal surgeries/post-surgical adhesions., Graphical abstract Image 1, Highlights of the findings and novelties • This study investigates the protective effects of saffron in preventing post-surgical adhesion band (PSAB) formation. • Saffron and crocin but not crocetin (i.p) decrease PSAB through anti-inflammatory and fibrinolytic mechanisms. • Our results support the therapeutic potential of saffron against PSAB-associated complications.

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: 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.