Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic gastrointestinal disorders associated with significant morbidity and complications. This study investigates the therapeutic potential of docosahexaenoic acid (DHA) in a trinitrobenzene sulfonic acid (TNBS) induced colitis model, focusing on inflammation, oxidative stress, and intestinal membrane permeability. Wistar albino rats were divided into Control, Colitis, and Colitis + DHA groups (n = 8–10/group). The Colitis and Colitis + DHA groups received TNBS intrarectally, while the Control group received saline. DHA (600 mg/kg/day) or saline was administered via gavage for six weeks. Macroscopic and microscopic evaluations of colon tissues were conducted. Parameters including occludin and ZO-1 expressions, myeloperoxidase (MPO) activity, malondialdehyde (MDA), glutathione (GSH), total antioxidant status (TAS), total oxidant status (TOS), Interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) levels were measured in colon tissues. Colitis induction led to significantly higher macroscopic and microscopic damage scores, elevated TOS levels, reduced occludin and ZO-1 intensity, decreased mucosal thickness, and TAS levels compared to the Control group (p < 0.001). DHA administration significantly ameliorated these parameters (p < 0.001). MPO, MDA, TNF-α, and IL-6 levels were elevated in the Colitis group but significantly reduced in the DHA-treated group (p < 0.001 for MPO, MDA; p < 0.05 for TNF-α and IL-6). DHA demonstrated antioxidant and anti-inflammatory effects by reducing reactive oxygen species production, enhancing TAS capacity, preserving GSH content, decreasing proinflammatory cytokine levels, preventing neutrophil infiltration, reducing shedding in colon epithelium, and improving gland structure and mucosal membrane integrity. DHA also upregulated the expressions of occludin and ZO-1, critical for barrier function. Thus, DHA administration may offer a therapeutic strategy or supplement to mitigate colitis-induced adverse effects.

Diabetes mellitus is a chronic metabolic disorder characterized by high blood sugar levels, which can lead to severe health issues if not managed effectively. Recent statistics indicate a significant global impact, with 463 million adults diagnosed worldwide and this projected to rise to 700 million by 2045. Type 1 diabetes is an autoimmune disorder where the immune system attacks pancreatic beta cells, reducing insulin production. Type 2 diabetes is primarily due to insulin resistance. Both types of diabetes are linked to severe microvascular and macrovascular complications if unmanaged. Microvascular complications, such as diabetic retinopathy, nephropathy, and neuropathy, result from damage to small blood vessels and can lead to organ and tissue dysfunction. Chronic hyperglycemia plays a central role in the onset of these complications, with prolonged high blood sugar levels causing extensive vascular damage. The emerging treatments and current research focus on various aspects, from insulin resistance to the intricate cellular damage induced by glucose toxicity. Understanding and intervening in these pathways are critical for developing effective treatments and managing diabetes long term. Furthermore, ongoing health initiatives, such as increasing awareness, encouraging early detection, and improving treatments, are in place to manage diabetes globally and mitigate its impact on health and society. These initiatives are a testament to the collective effort to combat this global health challenge.

Background and PurposeColorectal cancer (CRC) is the second most lethal disease, with high mortality due to its heterogeneity and chemo-resistance. Here, we have focused on the epidermal growth factor receptor (EGFR) as an effective therapeutic target in CRC and studied the effects of polyphenols known to modulate several key signalling mechanisms including EGFR signalling, associated with anti-proliferative and anti-metastatic properties.Experimental ApproachUsing ligand- and structure-based cheminformatics, we developed three potent, selective alkylaminophenols, 2-[(3,4-dihydroquinolin-1(2H)-yl)(p-tolyl)methyl]phenol (THTMP), 2-[(1,2,3,4-tetrahydroquinolin-1-yl)(4-methoxyphenyl)methyl]phenol (THMPP) and N-[2-hydroxy-5-nitrophenyl(4 & PRIME;-methylphenyl)methyl]indoline (HNPMI). These alkylaminophenols were assessed for EGFR interaction, EGFR-pathway modulation, cytotoxic and apoptosis induction, caspase activation and transcriptional and translational regulation. The lead compound HNPMI was evaluated in mice bearing xenografts of CRC cells.Key ResultsOf the three alkylaminophenols tested, HNPMI exhibited the lowest IC50 in CRC cells and potential cytotoxic effects on other tumour cells. Modulation of EGFR pathway down-regulated protein levels of osteopontin, survivin and cathepsin S, leading to apoptosis. Cell cycle analysis revealed that HNPMI induced G0/G1 phase arrest in CRC cells. HNPMI altered the mRNA for and protein levels of several apoptosis-related proteins including caspase 3, BCL-2 and p53. HNPMI down-regulated the proteins crucial to oncogenesis in CRC cells. Assays in mice bearing CRC xenografts showed that HNPMI reduced the relative tumour volume.Conclusions and ImplicationsHNPMI is a promising EGFR inhibitor for clinical translation. HNPMI regulated apoptosis and oncogenesis by modulating BCL-2/BAX and p53 in CRC cell lines, showing potential as a therapeutic agent in the treatment of CRC.

Objective: Inflammation is a complex reaction present in numerous disorders. Indomethacin, a compound possessing an indoline core, is a Nonsteroidal Anti-Inflammatory Drug (NSAID) that is commonly prescribed for inflammation and pain. The actin network, plays a major role in cellular activities and it's regulated by by Rho GTPases has important implications for cellular dynamics and orientation. In this research, we explore the effects of indomethacin on the inflammatory response as mediated via RhoA and pyrin inflammatory complexes using an inflammatory disease model with relation actin cytoskeleton. Materials and Methods: This study used Western blotting to examine the impact of indomethacin on the assembly processes related to the pyrin inflammasome complex and the RhoA signaling pathway in Lipopolysaccharide-stimulated THP-1 cells. Actin-indomethacin interaction was analyzed by Differential Scanning Fluorimetry (DSF). Results: We found that while the expression levels of pyrin decreased, phosphorylated-RhoA increased but overall RhoA levels did not change. The equilibrium dissociation constant (K-D) for the G-actin-indomethacin complex was calculated to be 9.591 +/- 1.608 ng/mL (R-2 = 0.8582) using triangle T-m measurements of indomethacin by DSF. Conclusion: Moreover, the effects of indomethacin on inflammation pathways may provide insight into the molecular mechanisms of pyrin inflammasome formation in various autoimmune diseases.

INTRODUCTION:Insulin resistance is associated with a pro-inflammatory state increasing the risk for complications in patients with type 2 diabetes mellitus (T2DM). In addition to its chronobiotic effects, the pineal hormone melatonin is known to exert anti-inflammatory and antioxidant effects. Melatonin was also suggested to affect insulin secretion. The aim of this study was therefore to investigate the effect of melatonin on inflammation in diabetic rats and to study the possible involvement of the melatonin receptor, MT2.MATERIALS AND METHODS:Male Sprague Dawley rats were randomly divided into four experimental groups (n = 10 per group): (1) control, (2) streptozotocin/nicotinamide induced diabetes type 2 (T2DM), (3) T2DM treated with melatonin (500 µg/kg/day), and (4) T2DM treated with melatonin (500 µg/kg/day for 6 weeks) and the selective MT2 receptor antagonist luzindole (0.25 g/kg/day for 6 weeks). Blood samples were taken for biochemical parameters and various tissue samples (liver, adipose tissue, brain) were removed for immunohistochemistry (IHC), Western blot (WB), and Q-PCR analyses, respectively.RESULTS:Melatonin significantly reduced increased blood levels of liver transaminases (AST, ALT), blood urea nitrogen (BUN), triglyceride, very low-density lipoprotein (VLDL), and cholesterol in diabetic rats with luzindole treatment partly reversing this effect regarding the lipids. Furthermore, the liver and adipose tissues of T2DM rats treated with melatonin showed lower expression of the inflammatory markers IL-1β, IL-6, TNF-α, and NF-κB as compared to the T2DM group without melatonin. The results also showed that the MT2 receptor is at least partly involved in the protective effects of melatonin.CONCLUSIONS:Our results suggest that melatonin exerts relevant anti-inflammatory effects on various tissues in type 2 diabetic rats.

Background: Insulin resistance is associated with a pro-inflammatory state increasing the risk for complications in patients with type 2 diabetes mellitus (T2DM). In addition to its chronobiotic effects, the pineal hormone melatonin is also known to exert anti-inflammatory and antioxidant effects. Furthermore, melatonin was also suggested to affect insulin secretion and melatonin levels were reported to be decreased in T2DM patients Aims: The aim of this study was therefore to investigate the effect of melatonin on inflammation in diabetic rats and to study the possible involvement of the melatonin receptor, MT2. Materials and Methods: Male Sprague Dawley rats were randomly divided into four experimental groups (n = 10 per group):1) control, 2) streptozotocin/nicotinamid induced diabetes type 2 (T2DM), 3) T2DM treated with melatonin (500 µg/kg/day), and 4) T2DM treated with melatonin (500 µg/kg/day) and the selective MT2 receptor antagonist luzindole (0.25 g/kg/day). Blood samples were taken for biochemical parameters and various tissue samples (liver, adipose tissue, brain) were removed for immunohistochemistry (IHC), western blot (WB) and Q-PCR analyses, respectively. Results: Melatonin significantly reduced increased blood levels of liver transaminases (AST, ALT) and blood urea nitrogen (BUN) in diabetic rats. Furthermore, in liver and adipose tissue of treated rats, melatonin administration resulted in considerable lower expression of the increased inflammatory markers IL-1β, IL-6, TNF-α and NF-κB, as shown by reduction in RNA and protein levels. The MT2 receptor was only partly involved in the anti-inflammatory effects of melatonin. Conclusions: Our results suggest that melatonin has relevant anti-inflammatory effects in diabetic rats. Further studies in humans could prove the potential clinical benefit of melatonin supplementation in patients with T2DM.

Objectives:Proposals for scientific studies must have an original hypothesis and the appropriate design and methodology to test the premise.Methods:This study is an evaluation of the suitability of applications submitted to a local ethics committee (EC) and the rate of publication of that research.Results:A total of 899 files submitted for EC approval were retrospectively assessed. The EC found that the description of the methods in 44% of the applications was inaccurate, and that this type of error was most often seen in submissions from the surgical branch. In all, 52% of the applications for which we were informed about their final status were not published.Conclusion:The results suggest that improved training in epidemiology is required to reduce the number of application errors and that new regulations could help to motivate healthcare personnel to conduct scientific research and publish their findings.

La poliquistosis renal autosómica dominante es la enfermedad renal hereditaria más frecuente aunque los datos disponibles generalmente son tras el inicio del tratamiento renal sustitutivo.Conocer la situación global de la poliquistosis renal autosómica dominante en el ámbito sanitario de Granada.Desde enero 2007 hasta diciembre 2016 hemos recogido información clínica, familiar y demográfica de todos los pacientes con poliquistosis renal autosómica dominante, estuvieran o no en tratamiento renal sustitutivo, atendidos en el área de Granada. Se han utilizado los programas informáticos SPSS 15.0 y GenoPro.Mil ciento siete pacientes diagnosticados, el 50,6% son varones. Se han estudiado 4-6 generaciones/familia. El 99,1% de raza caucásica. Hay áreas geográficas con mayor concentración. No hay antecedentes familiares en el 2,43%. La edad media de diagnóstico es de 34 ± 17,8 años y en el 57,7% de los casos, el diagnóstico se produce después de tener descendencia. El principal motivo de diagnóstico son los antecedentes familiares (46,4%). La edad media de entrada en técnica es de 54,2 ± 11,05 años. El 96,3% de los fallecidos tenían algún grado de insuficiencia renal en el momento del exitus. La edad media del exitus es de 60,9 ± 14,10 años, siendo desconocida la principal causa de muerte (33,5%) seguida de la cardiovascular (27,8%).Casos y familias se concentran en algunas áreas geográficas, un número importante de individuos están sin diagnosticar, fallecen antes por causa cardiovascular y se diagnostican tarde respecto al momento reproductivo. Dado que no hay tratamiento curativo, la estrategia de prevención primaria mediante el diagnóstico genético preimplantacional adquiere protagonismo.Although autosomal dominant polycystic kidney disease is the most common hereditary kidney disease, available data tend to be limited to after initiation of renal replacement therapy.To ascertain an overview of autosomal dominant polycystic kidney disease within the health area of Granada in southern Spain.From January 2007 to December 2016, we collected clinical, family and demographic information about all patients with autosomal dominant polycystic kidney disease, irrespective of whether or not they were treated with RRT, in the Granada health area. The computer software SPSS 15.0 and GenoPro were used.50.6% of the 1,107 diagnosed patients were men. 99.1% were Caucasian and 4–6 generations/family were studied. The geographical distribution was heterogeneous. There was no family history in 2.43%. The mean age of diagnosis was 34.0 ± 17.80 years and the diagnosis was made after having offspring in 57.7% of cases. The main reason for diagnosis was family history (46.4%). The mean age of initiation of renal replacement therapy was 54.2 ± 11.05 years. 96.3% of the deceased had some degree of renal failure at the time of death. The mean age of death was 60.9 ± 14.10 years, the main cause of death being unknown in 33.5% of cases, followed by cardiovascular (27.8%).Cases and families were concentrated in certain geographical areas and a significant number of individuals were undiagnosed prior to cardiovascular death or diagnosed late after reproduction. Given that there is currently no curative treatment, the primary prevention strategy of preimplantation genetic diagnosis should play a leading role.

The major cause of morbidity and mortality in diabetes mellitus is cardiovascular disease. Coronary atherosclerosis and cardiomyopathy occur as a result of metabolic abnormalities and hyperglycemia associated with diabetes [1]. An abnormal increase in blood glucose was found to be related with cardiomyocyte to death by apoptosis. Apoptosis, result of myocardial abnormalities might be an important cause of cardiomyopathy [2]. Consequences of such abnormalities occur in diabetes and the contractile function of the heart is ultimately altered. The electro-cardiogram of many diabetes patients show several alterations from normal patterns. Increase of QT interval duration is one of them. Increase of QT interval reflects the abnormalities of ventricular myocardial re polarization. Prolongation of QT interval has been associated with sudden death in diabetes patients [3-4].

Growing evidence has been reported on adriamycin (ADR) hepatotoxicity in literature. Hepatotoxicity caused by the use of drugs has a serious undesirable effect in the cure of cancer patients that needs to be eliminated. The exact mechanism of ADR on non-cancerous tissue still remains to be a mystery. The zeolite (clinoptilolite) minerals form a complex group of aluminosilicates that often occur as accessory minerals in intermediate and basic rocks. In light of this information, we investigated the possible anti-inflammatory and anti-apoptotic effects of clinoptilolite in ADR that is inducing the toxicity in primary liver cell culture. Primary liver cell culture from rat was used in the study. We had three experiment groups including the following: (1) cells treated only with 50 μM ADR for 24 h, (2) cells treated with the 50 μM ADR for 24 h and then treated with 10−4 M zeolite for 1 h, and (3) cells were incubated with 50 μM ADR for 24 h and then incubated with 10−4 M zeolite for 24 h to test its long-term effects. After that, western blotting was performed in order to evaluate protein expression levels of several inflammation markers including IL-1β, tumor necrosis factor (TNF)-α, and nuclear factor kappa B (NF-κB), and immunohistochemistry was carried out to detect apoptosis in liver cell culture. Also, TdT–dUTP Terminal Nick-End Labeling (TUNEL) method was used for detecting apoptosis. We found elevated levels of inflammatory protein and apoptotic markers in ADR-administered cells (p < 0.05). Inflammatory and apoptotic markers decreased significantly after treated with zeolite (p < 0.05). The present study was pointed out that ADR causes hepatotoxicity via apoptosis and/or inflammation processes resulting from initiator NF-κB and TNF which causes proinflammatory mediators such as IL-1β. Elevation of inflammation might give rise to trigger apoptosis. Clinoptilolite counteracted the apoptosis and inflammation induced by ADR arising from the decrease in NF-κB, TNF-α, and IL-1β protein levels.

To analyze the characteristics of smokers treated with acupuncture for smoking cessation in Hong Kong.A total of 2051 subjects were recruited in a clinical pilot research project “acupuncture for smoking cessation”, which was conducted jointly by Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences and Hong Kong Pok Oi Hospital from January of 2011 to December of 2013. The characteristics of study subjects, including baseline information, smoking background, intention to quit and influencing factors were analyzed.The majority of subjects treated with acupuncture for smoking cessation in Hong Kong was male (66.7%), but the proportion of female smokers in this study (33.3%) was higher than that of female smokers in Hong Kong population (13.8%, P < 0.05). Subjects were at the mean age of 43.83 years old, of which the percentage of females aged 31–40 years was the highest (38.8%, P < 0.05). The mean duration of smoking was 25.49 years. The number of cigarettes smoked per day was 17.57 cigarettes. Fagerstrom Test for Nicotine Dependence (FTND) was 5.29 points. Most of the subjects had attempted quitting smoking (81.42%). The confidence index (7.44 points) and the readiness to quit smoking (8.13 points) were high. Subjects quitting smoking were mostly due to health cause (81.91%). The majority of subjects were at the level of middle school (61.63%). The higher the educational level was, the lower the tobacco dependence was and the higher the confidence in successfully quitting smoking was. 50.27% of subjects chose acupuncture for smoking cessation mainly through friends, television and network publicity. Subjects who had received acupuncture had the highest confidence index, while those who wanted to try a new method had the lower confidence index.Acupuncture for smoking cessation was more popular in female smokers, especially those aged 31–40 years. The effectiveness of acupuncture-smoking cessation was most significant in the smokers over 60.

Bacterial resistance to antibiotics is increasing worldwide. Antibiotic-resistant strains can lead to serious problems regarding treatment of infection. Carbapenem antibiotics are the final treatment option for infections caused by serious and life-threatening multidrug-resistant gram-negative bacteria. Therefore, an understanding of carbapenem resistance is important for infection control. In the study described herein, the phenotypic and genotypic features of carbapenem-resistant Enterobacteriaceae strains isolated in our hospital were evaluated.

Nitric oxide (NO) plays a significant role in the development of diabetic nephropathy. We investigated the effects of an antioxidant, carnosine, on streptozotocin (STZ)-induced renal injury in diabetic rats. We used four groups of eight rats: group 1, control; group 2, carnosine treated; group 3, untreated diabetic; group 4, carnosine treated diabetic. Kidneys were removed and processed, and sections were stained with periodic acid-Schiff (PAS) and subjected to eNOS immunohistochemistry. Examination by light microscopy revealed degenerated glomeruli, thickened basement membrane and glycogen accumulation in the tubules of diabetic kidneys. Carnosine treatment prevented the renal morphological damage caused by diabetes. Moreover, administration of carnosine decreased somewhat the oxidative damage of diabetic nephropathy. Appropriate doses of carnosine might be a useful therapeutic option to reduce oxidative stress and associated renal injury in diabetes mellitus.

Diabetic nephropathy is one of the most serious complications of diabetes and the major cause of end-stage renal failure. Consequences of diabetic nephropathy include increased kidney size and glomerular volume, thickening of basement membranes and progressive accumulation of extracellular matrix. Reports in the literature support an association between increased secretion of inflammatory molecules, such as cytokines, growth factors and metalloproteinases, and development of diabetic nephropathy. We investigated the potential of granulocyte colony- stimulating factor (G-CSF) as a therapeutic candidate for preventing diabetic nephropathy. We used 21 8-week-old male rats; 14 were administered a single dose of 60 mg/kg streptozotocin (STZ) to induce diabetes. The rats were divided into three groups of seven: group 1, control; group 2, diabetic; group 3, diabetic plus G-CSF treatment. After 4 weeks, immunoexpressions of transforming growth factor β1 (TGF-β1), Akt and CD34 levels were measured in the kidney tissue. Blood glucose, urine protein and the glomerular area also were measured for each group. We found that G-CSF treatment decreased TGF-β1 immunoexpression, urine protein and glomerular area in kidneys of diabetic rats, and increased CD 34 and Akt immunoexpression in kidneys of diabetic rats. The effects of G-CSF were independent of blood glucose levels. G-CSF may be a useful therapeutic agent for preventing diabetic nephropathy.

Background: Chronic kidney disease (CKD) is a major health problem worldwide. Oxidative stress is one of the mediators of this disease. Systemic complications of oxidative stress are involved in the pathogenesis of hypertension, endothelial dysfunction, shortened erythrocyte lifespan, deformability, and nitric oxide (NO) dysfunction. L-carnosine is known as an antioxidant. In this study, our aim was to investigate the effect of carnosine on hemorheologic and cardiovascular parameters in CKD-induced rats.Material/Methods: We used 4-month-old male Sprague-Dawley rats divided into 4 groups of 6 rats each. Three days after subtotal nephrectomy and sham operations, the surviving rats were divided into the 4 groups; 1) Sham (S), 2) Sham+Carnosine (S-C), 3) Subtotal nephrectomy (Nx), and 4) Subtotal nephrectomy + Carnosine (N-C). Carnosine was injected intraperitoneally (i.p.) (50 mg/kg) for 15 days. The control group received the same volume of physiological saline.Results: In CKD rats, malondialdehyde (MDA) levels were increased, and NO and RBC deformability were decreased compared to Sham. Carnosine treatment decreased MDA levels, improved RBC (red blood cell) ability to deform, and increased NO levels. However, carnosine did not affect blood pressure levels in these rats.Conclusions: We found that carnosine has beneficial effects on CKD in terms of lipid peroxidation and RBC deformability. Carnosine may have a healing effect in microcirculation level, but may not have any effect on systemic blood pressure in CKD-induced rats.