Urinary biomarkers in diabetic nephropathy.

Diabetic nephropathy (DN), a significant consequence of diabetes, is associated with adverse cardiovascular and renal disease as well as mortality. Although microalbuminuria is considered the best non-invasive marker for DN, better predictive markers are needed of sufficient sensitivity and specificity to detect disease in general and in early disease specifically. Even prior to appearance of microalbuminuria, urinary biomarkers increase in diabetics and can serve as accurate nephropathy biomarkers even in normoalbuminuria. In this review, a number of novel urine biomarkers including those reflecting kidney damage caused by glomerular/podocyte damage, tubular damage, oxidative stress, inflammation, and intrarenal renin-angiotensin system activation are discussed. Our review also includes emerging biomarkers such as urinary microRNAs. These short noncoding miRNAs regulate gene expression and could be utilized to identify potential novel biomarkers in DN development and progression. .

Synthesis and characterization of a green and recyclable arginine-based palladium/CoFe2O4 nanomagnetic catalyst for efficient cyanation of aryl halides.

The utilization of magnetic nanoparticles in the fields of science and technology has gained considerable popularity. Among their various applications, magnetic nanoparticles have been predominantly employed in catalytic processes due to their easy accessibility, recoverability, effective surface properties, thermal stability, and low cost. In this particular study, cyanuric chloride and arginine were utilized to synthesize an arginine-based oligomeric compound (ACT), which was supported on cobalt ferrite, resulting in a green catalyst with high activity and convenient recyclability for the cyanation reaction of aryl halides. The Pd/CoFe2O4@ACT nanomagnetic catalyst demonstrated excellent performance in the cyanation of various aryl iodides and bromides, yielding favorable reaction outcomes at a temperature of 90 °C within a duration of 3 hours. The synthesized nanoparticles were successfully characterized using various techniques, including FTIR, FE-SEM, EDX/MAP, XRD, TEM, TGA, BET, and ICP-OES. Moreover, the Pd/CoFe2O4@ACT catalyst exhibited remarkable catalytic activity, maintaining an 88% performance even after five consecutive runs. Analysis of the reused catalyst through SEM and TEM imaging confirmed that there were no significant changes in the morphology or dispersion of the particles. Ultimately, it was demonstrated that the Pd/CoFe2O4@ACT nanomagnetic catalyst outperformed numerous catalysts previously reported in the literature for the cyanation of aryl halides.

Mechanism of action and neuroprotective role of nicorandil in ischemic stroke.

Nicorandil is a dual mechanism anti-anginal agent that acts as a nitric oxide (NO) donor and a potassium (K+) channel opener. Recent studies have evaluated the effect of nicorandil on ischemic stroke. Neurons have a low tolerance to hypoxia and therefore the brain tissue is significantly vulnerable to ischemia. Current approved treatments for ischemic stroke are tissue plasminogen activators and clot retrieval methods. The narrow therapeutic time window and lack of efficacy in restoring the dying neurons urge researchers to develop an alternative approach. In the terminal stages of anoxia, K+ channels induce hyperpolarization in various types of neuronal cells, leading to decreased neuronal activity and the preservation of the brain's energy. Nicorandil can open these K+ channels and sustain the hyperpolarization phase, which may have a neuroprotective effect during hypoxia. Additionally, we review how nicorandil can improve overall stroke outcomes through its anti-inflammatory, anti-oxidative, and edema-reducing effects. One of the major components evaluated in stroke patients is blood pressure. Studies have demonstrated that the effect of nicorandil on blood pressure is related to both its K+ channel opening and NO donating mechanisms. Since both hypertension and hypotension need correction before stroke intervention, it's crucial to consider the role of nicorandil and its impact on blood pressure. Previously published studies indicate that the right dosage of nicorandil can improve cerebral blood flow without significant changes in hemodynamic profiles. In this review, we discuss how nicorandil may contribute to better stroke outcomes based on previously published literature and laboratory findings.

Diabetes and ovarian cancer: risk factors, molecular mechanisms and impact on prognosis.

BACKGROUND AND AIM: Diabetes mellitus has been linked to a lower rate of cancer survival and an increase in the incidence of most malignancies. Investigations showed that diabetes might affect ovarian cancer (OC) prognosis and survival. Based on the current information, this study intends to review the risk factors, molecular pathways, and impact of diabetes on OC. METHODS: The data was derived from online databases, including Web of Science, PubMed, and Scopus. The inclusion criteria were original studies, which included the risk factors, molecular mechanisms, and impact of diabetes on OC. The effect of different antidiabetic drugs was also discussed in this manuscript. All of the clinical, in vivo, and in vitro studies were included in the present study. RESULTS: The diagnosis of diabetes mellitus negatively affects the survival and prognosis in OC cases. The epidemiologic data shows that the risk of OC increases in patients with diabetes mellitus compared to the healthy population. Insulin-like growth factors family was raised in diabetic patients, which target several mechanisms, including targeting oxidative stress, angiogenesis, and tumor markers. Antidiabetic drugs such as metformin, sitagliptin, and rosiglitazone have a promising effect on elongation of survival and enhancement of prognosis in OC patients. CONCLUSIONS: Diabetes mellitus is a significant risk factor for OC in women, and it negatively impacts survival and prognosis. Molecular mechanisms such as IGF family, oxidative stress, and inflammatory cytokines have been identified to explain this relationship. Antidiabetic drugs like metformin, sitagliptin, and rosiglitazone have shown promise in improving survival and prognosis of OC patients.

Training in child care and carrying out auriculotherapy techniques for mothers of premature newborns: double-blind clinical trial / Treinamento em cuidados infantis e técnicas de auriculoterapia a mães de recém-nascidos prematuros: ensaio clínico duplo-cego

Abstract Objectives: this study aimed to investigate the effect of education and auriculotherapy on stress, anxiety, and depression, and coping responses in mothers with premature infants. Methods: this is a randomized clinical trial study at Bahar Hospital carried out with 90 mothers with premature infants admitted to the neonatal intensive care unit. Those eligible for hospitalization were included in the study and distributed into three groups before intervention: (30 ones in the control, training, and auriculotherapy groups, respectively). The mean stress, anxiety, depression, and coping responses in mothers were measured both at the beginning of the study and before neonatal discharge. Results: there was no statistically significant difference in terms of anxiety, stress, and depression scores between the three groups before the intervention. However, after the intervention, there was a significant statistical difference between these three groups, which was among the mean scores of anxiety, stress, and depression. In terms of coping responses, the mean emotional and problem-oriented score in all three groups before and after the intervention is statistically significant. Conclusions: educating mothers and auriculotherapy pressure therapy are simple and practical methods in reducing anxiety, stress, depression, and increase coping responses; consequently, they can be used in neonatal intensive care.

Resumo Objetivos: este estudo teve como objetivo investigar o efeito da educação e da auriculoterapia no estresse, ansiedade e depressão e nas respostas de enfrentamento em mães com bebês prematuros. Métodos: este é um estudo de ensaio clínico randomizado no Bahar Hospital realizado com 90 mães de bebês prematuros internados em unidade de terapia intensiva neonatal. Os elegíveis para internação foram incluídos no estudo e distribuídos em três grupos antes da intervenção: (30 nos grupos controle, treinamento e auriculoterapia, respectivamente). O estresse médio, ansiedade, depressão e respostas de enfrentamento em mães foram medidas no início do estudo e antes da alta neonatal. Resultados: não houve diferença estatisticamente significativa nos escores de ansiedade, estresse e depressão entre os três grupos antes da intervenção. No entanto, após a intervenção, houve uma diferença estatística significativa entre esses três grupos, que foi entre a pontuação média de ansiedade, estresse e depressão. Em termos de respostas de enfrentamento, a pontuação média emocional e orientada para o problema em todos os três grupos antes e depois da intervenção é estatisticamente significativa. Conclusões: a educação das mães e a terapia de pressão com auriculoterapia são métodos simples e práticos na redução da ansiedade, estresse, depressão e aumento das respostas de enfrentamento; conseqüentemente, podem ser utilizados em terapia intensiva neonatal.

The Important Role of Interleukin-2 in COVID-19.

There is controversial literature about the effects of the interleukin-2 (IL-2) cytokine family in COVID-19 pathogenesis and immunity. So we aimed to identify the potential in the role of the IL-2 family in COVID-19. A narrative review search was done through online databases, including PubMed, Scopus, and Web of Science. The search deadline was up to December 2022. We applied no time limits for the searching strategy. After retrieving articles from the databases, the authors summarized the data into two data extraction tables. The first data extraction table described the changes in the IL-2 cytokine family in COVID-19 and the second table described the therapeutic interventions targeting IL-2 family cytokines. The results of the literature on the role of the IL-2 cytokine family do not show a singular rule. IL-2 cytokine family can change during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Some studies suggest that IL-2 cytokine family rise during the infection and cause severe inflammatory response and cytokine storm. These cytokines are shown to be increased in immunocompromised patients and worsen their prognosis. In individuals without underlying disease, the upregulation of the IL-2 family shows the clinical outcome of the disease and rises with disease severity. However, some other studies show that these cytokines do not significantly change. IL-2 cytokine family is mostly upregulated in healthy individuals who had vaccination, but immunocompromised patients did not show significant changes after a single dose of vaccines, which shows that these patients need booster doses for efficient immunity. IL-2 cytokine family can also be used as immunotherapy agents in COVID-19.

Renal vascular responses to angiotensin II infusion in two kidneys-one clip hypertensive rats under partial ischemia/reperfusion with and without ischemia preconditioning: the roles of AT1R blockade and co-blockades of AT1R and MasR.

Background and purpose: The renin-angiotensin system activation, partial ischemia/reperfusion (IR) injury, and hypertension contribute to the development of acute kidney injury. The study aims to look at the vascular responses of angiotensin II (Ang II) during Ang II type 1 receptor (AT1R) blockade (losartan) or co-blockades of AT1R and Mas receptor (A779) in two kidneys one clip (2K1C) hypertensive rats which subjected to partial IR injury with and without ischemia preconditioning (IPC). Experimental approach: Thirty-three 2K1C male Wistar rats with systolic blood pressure ≥ 150 mmHg were divided into three groups of sham, IR, and IPC + IR divided into two sub-groups receiving losartan or losartan + A779. The IR group had 45 min partial kidney ischemia, while the IPC + IR group had two 5 min cycles of partial ischemia followed by 10 min of reperfusion and then 45 min of partial kidney ischemia followed by reperfusion. The sham group was subjected to similar surgical procedures except for IR or IPC. Findings/Results: Ang II increased mean arterial pressure in all the groups, but there were no significant differences between the sub-groups. A significant difference was observed in the renal blood flow response to Ang II between two sub-groups of sham and IR groups treated with AT1R blockade alone or co-blockades of AT1R + A779. Conclusion and implications: These findings demonstrated the significance of AT1R and Mas receptor following partial renal IR in the renal blood flow responses to Ang II in 2K1C hypertensive rats.

Liquid biopsy in ovarian cancer: advantages and limitations for prognosis and diagnosis.

Ovarian cancer (OC) is a highly fatal gynecologic malignancy, often diagnosed at an advanced stage which presents significant challenges for disease management. The clinical application of conventional tissue biopsy methods and serological biomarkers has limitations for the diagnosis and prognosis of OC patients. Liquid biopsy is a novel sampling method that involves analyzing distinctive tumor elements secreted into the peripheral blood. Growing evidence suggests that liquid biopsy methods such as circulating tumor cells, cell-free RNA, circulating tumor DNA, exosomes, and tumor-educated platelets may improve early prognosis and diagnosis of OC, leading to enhanced therapeutic management of the disease. This study reviewed the evidence demonstrating the utility of liquid biopsy components in OC prognosis and diagnosis, and evaluated the current advantages and limitations of these methods. Additionally, the existing obstacles and crucial topics for future studies utilizing liquid biopsy in OC patients were discussed.

Mechanism of action and therapeutic potential of dimethyl fumarate in ischemic stroke.

Dimethyl fumarate (DMF) is an immunomodulatory drug currently approved for the treatment of multiple sclerosis and psoriasis. Its benefits on ischemic stroke outcomes have recently come to attention. To date, only tissue plasminogen activators (tPAs) and clot retrieval methods have been approved by the FDA for the treatment of ischemic stroke. Ischemic conditions lead to inflammation through diverse mechanisms, and recanalization can worsen the state. DMF and the nuclear factor erythroid-derived 2-related factor 2 (Nrf2) pathway it regulates seem to be important in postischemic inflammation, and animal studies have demonstrated that the drug improves overall stroke outcomes. Although the exact mechanism is still unknown, studies indicate that these beneficial impacts are due to the modulation of immune responses, blood-brain barrier permeability, and hemodynamic adjustments. One major component evaluated before, during, and after tPA therapy in stroke patients is blood pressure (BP). Recent studies have found that DMF may impact BP. Both hypotension and hypertension need correction before treatment, which may delay the appropriate intervention. Since BP management is crucial in managing stroke patients, it is important to consider DMF's role in this matter. That being said, it seems further investigations on DMF may lead to an alternative approach for stroke patients. In this article, we discuss the mechanistic roles of DMF and its potential role in stroke based on previously published literature and laboratory findings.

The Role of the Ectopeptidase APN/CD13 in Cancer.

APN/CD13 is expressed in a variety of cells/tissues and is therefore associated with diverse physiological functions, including proliferation, differentiation, migration, angiogenesis, invasion, metastasis, vasoconstriction, and the regulation of normal and impaired immune function. Increased expression or activity of APN/CD13 has been described for various tumors, such that APN/CD13 is in most cases associated with reduced disease-free and overall survival. The mechanisms that mediate these cellular effects of APN/CD13 have been largely determined and are described here. APN/CD13-regulated signaling pathways include integrin recycling, the regulation of small GTPase activities, cell-ECM interactions, and Erk1/2, PI3K, and Wnt signaling. APN/CD13 is a neo-angiogenesis marker that is not found on normal endothelia, but it is found on neo-angiogenetically active endothelia. Therefore, APN/CD13 represents a specific receptor for so-called "tumor-homing peptides" (NRG peptides). Peptides containing the NRG motif show high-affinity binding to APN/CD13. APN/CD13 thus represents a versatile target for the inhibition of tumor-induced angiogenesis through the tumor-selective administration of, e.g., cytotoxic substances. Furthermore, it enables the molecular imaging of tumor masses and the assessment of (neo)angiogenesis in animal models and in patients. Pharmacological inhibitors of APN/CD13 have been proven to reduce tumor growth and tumor progression in various APN/CD13-positive tumors.

Magnetically separable triazine-based Cu(ii)-vitamin B5 complex in nitromethane toward efficient heterogeneous cyanation reaction of aryl halides.

In the current study, a highly efficient heterogeneous copper catalyst has been developed by supporting copper acetate on a magnetically separable triazine-vitamin B5 system. After the successful characterization of the prepared nanoparticles by various techniques such as FT-IR, FE-SEM, EDX/MAP, XRD, TEM, TGA, VSM, and ICP-OES, the catalytic efficiency of them were evaluated in the cyanation reaction of aryl halides in the presence of nitromethane as a non-toxic and cost-effective cyanation source. The cyanation products were obtained in desirable yields. Notably, the magnetic nanocatalyst can be easily recovered and reused at least five times without a significant decrease in its performance.

Evaluation of the gene encoding carnitine transporter (OCTN2/SLC22A5) expression in human breast cancer and its association with clinicopathological characteristics.

BACKGROUND: Fatty acid oxidation (FAO) is a major energy-generating process in the mitochondria and supports proliferation, growth, and survival of cancer cells. L-Carnitine is an essential co-factor for carrying long-chain fatty acids into the mitochondria. The entry of l-carnitine across cell membrane is regulated by OCTN2 (SLC22A5). Thus, it can plays a significant role in the mitochondrial fatty acid oxidation. This study aimed to evaluate the OCTN2 expression and its association with clinicopathological characteristics in breast cancer. METHODS: In this work, OCTN2 was examined in 54 pairs of fresh samples of breast cancer (BC) and adjacent noncancerous tissue using quantitative real-time polymerase chain reaction and immunohistochemistry (IHC). The IHC approach was also used to investigate the expression of additional clinicopathological features. RESULTS: The present research findings revealed that the relative expression of OCTN2 in BC tissues was substantially higher than the adjacent normal tissues. This up-regulation was correlated positively with tumor size and Ki-67 and negatively with the progesterone receptor (PR) status, providing evidence of the opposite effects of OCTN2 and PR on tumor development. CONCLUSION: The study shows that the OCTN2 expression in BC patients may be used as a prognostic biomarker and a tumor oncogene. As a result, it could be considered a possible therapeutic target. Nevertheless, the significance of the findings needs to be confirmed by further studies.

View of the Renin-Angiotensin System in Acute Kidney Injury Induced by Renal Ischemia-Reperfusion Injury.

Renal ischemia-reperfusion injury (RIRI) is a sequence of complicated events that is defined as a reduction of the blood supply followed by reperfusion. RIRI is the leading cause of acute kidney injury (AKI). Among the diverse mediators that take part in RIRI-induced AKI, the renin-angiotensin system (RAS) plays an important role via conventional (angiotensinogen, renin, angiotensin-converting enzyme (ACE), angiotensin (Ang) II, and Ang II type 1 receptor (AT1R)) and nonconventional (ACE2, Ang 1-7, Ang 1-9, AT2 receptor (AT2R), and Mas receptor (MasR)) axes. RIRI alters the balance of both axes so that RAS can affect RIRI-induced AKI. In overall, the alteration of Ang II/AT1R and AKI by RIRI is important to consider. This review has looked for the effects and interactions of RAS activities during RIRI conditions.

Immunogenicity of COVID-19 vaccines in patients with diabetes mellitus: A systematic review.

Purpose: To evaluate the immunogenicity of COVID-19 vaccines in patients with diabetes mellitus (DM) through a systematic approach. Method: A comprehensive search was conducted in PubMed, Scopus, and Web of Science with no time restrictions. The search was based on the three main concepts: Covid-19, Vaccine immunogenicity and Diabetes Mellitus. Results: After excluding irrelevant studies, 16 studies remained for the quantitative assay. Among the sixteen studies, eleven had controls. Type of diabetes was specifically mentioned in six studies (T2DM; n=4, T1DM and T2DM; n=2). Twelve of the included studies were conducted on the immunogenicity of vaccines that included mRNA vaccines (i.e. BNT162b2 and mRNA-1273) in DM, five studies included vector-based vaccines (i.e. Ad5-nCoV and ChAdOx1-S), and five studies assessed the immunogenicity of vaccines in DM, including inactivated vaccines (i.e. BBV-152, CoronaVac, Sinopharm or SinoVac). Most of the current studies indicate lower antibody response in patients with DM compared to individuals without DM, after the second dose of vaccine and irrespective of vaccine type. Several studies have shown that higher age and higher BMI are associated with lower antibody response, while optimum glycemic control and higher GFR are associated with higher antibody response among patients with DM. Conclusion: Immunogenicity of the vaccines has mostly been reported to be lower among patients with DM compared to healthy controls. There are also few studies assessing variables that significantly affect this association, including age, type of diabetes, BMI, glycemic control and eGFR. Investigating these associations could help us provide the most advantageous condition for patients with DM before, during and after vaccination for optimum antibody response. Many unresolved issues concerning potential factors affecting vaccine immunogenicity, including type of vaccine, numbers of administered doses, re-vaccination intervals and hyperglycemia in patients with DM need to be addressed through future research.

The barriers to whole-grain consumption among Iranian students.

Studies show that regularly consuming whole grains reduce the risk of obesity and a wide range of chronic diseases. Despite this, studies reveal that students are consuming fewer whole grains. In the present study, we aimed to investigate the barriers to the consumption of whole grains among Iranian students. This cross-sectional study examined students at Fasa, Iran in 2020-2021. The online questionnaires were completed by students after receiving informed consent. Statistical analysis was performed using SPSS 26 and Chi-square, t-test, and logistic regression (P > 0.05). The current study involved 1890 students (1287 (68.1%) girls and 603 (31.9%) boys). Despite the preference for white flour bread among 53.8% of all students, 77.4% ate other whole-grain products, and 75.2% consumed all products at least once a week. Additionally, barriers such as access issues (70.5%), family supply issues (91.8%), lack appeal (72.8%), non-consumption by classmates (96.2%), and high prices in recent years (43.9%) were identified as obstacles to whole grain consumption. Furthermore, white bread eating students had significantly lower appetite levels and tended to eat fast food more often than those who ate whole grains (P < 0.05). We found that slightly more than half of the participants preferred to eat bread prepared with refined flour. Several other factors, including lack of access, lack of attractiveness, product price, parents not purchasing whole-grain products, students not paying attention to nutrition labels, peers' effect, and eating with friends instead of family, also contribute to students avoiding whole-grain products.

Pathological Mechanisms Induced by TRPM2 Ion Channels Activation in Renal Ischemia-Reperfusion Injury.

Renal ischemia-reperfusion (IR) injury triggers a cascade of signaling reactions involving an increase in Ca2 + charge and reactive oxygen species (ROS) levels resulting in necrosis, inflammation, apoptosis, and subsequently acute kidney injury (AKI).Transient receptor potential (TRP) channels include an essential class of Ca2+ permeable cation channels, which are segregated into six main channels: the canonical channel (TRPC), the vanilloid-related channel (TRPV), the melastatin-related channel (TRPM), the ankyrin-related channel (TRPA), the mucolipin-related channel (TRPML) and polycystin-related channel (TRPP) or polycystic kidney disease protein (PKD2). TRP channels are involved in adjusting vascular tone, vascular permeability, cell volume, proliferation, secretion, angiogenesis and apoptosis.TRPM channels include eight isoforms (TRPM1-TRPM8) and TRPM2 is the second member of this subfamily that has been expressed in various tissues and organs such as the brain, heart, kidney and lung. Renal TRPM2 channels have an important role in renal IR damage. So that TRPM2 deficient mice are resistant to renal IR injury. TRPM2 channels are triggered by several chemicals including hydrogen peroxide, Ca2+, and cyclic adenosine diphosphate (ADP) ribose (cADPR) that are generated during AKI caused by IR injury, as well as being implicated in cell death caused by oxidative stress, inflammation, and apoptosis.

Therapeutic Efficacy of Oncolytic Viruses in Fighting Cancer: Recent Advances and Perspective.

Immunotherapy is at the cutting edge of modern cancer treatment. Innovative medicines have been developed with varying degrees of success that target all aspects of tumor biology: tumors, niches, and the immune system. Oncolytic viruses (OVs) are a novel and potentially immunotherapeutic approach for cancer treatment. OVs reproduce exclusively in cancer cells, causing the tumor mass to lyse. OVs can also activate the immune system in addition to their primary activity. Tumors create an immunosuppressive environment by suppressing the immune system's ability to respond to tumor cells. By injecting OVs into the tumor, the immune system is stimulated, allowing it to generate a robust and long-lasting response against the tumor. The essential biological properties of oncolytic viruses, as well as the underlying mechanisms that enable their usage as prospective anticancer medicines, are outlined in this review. We also discuss the increased efficacy of virotherapy when combined with other cancer medications.

Review article epithelial to mesenchymal transition­associated microRNAs in breast cancer.

Despite major advances, breast cancer (BC) is the most commonly diagnosed carcinoma and remains a deadly disease among women worldwide. Many researchers point toward an important role of an epithelial to mesenchymal transition (EMT) in BC development and promoting metastasis. Here, will be discussed that how functional changes of transcription factors, signaling pathways, and microRNAs (miRNA) in BC promote EMT. A thorough understanding the EMT biology can be important to determine reversing the process and design treatment approaches. There are frequent debates as to whether EMT is really relevant to BC in vivo, in which due to the intrinsic heterogeneity and tumor microenvironment. Nevertheless, given the importance of EMT in cancer progression and metastasis, the implementation of therapies against cancer-associated EMT will continue to help us develop and test potential treatments.

Mas Receptor Blockade Promotes Renal Vascular Response to Ang II after Partial Kidney Ischemia/Reperfusion in a Two-Kidney-One-Clip Hypertensive Rats Model.

BACKGROUND: Partial kidney ischemia-reperfusion (IR) injury is the principal cause of acute kidney injury. The renin-angiotensin system (RAS) and hypertension also may be influenced by renal IR injury. In two models of partial renal IR with and without ischemia preconditioning (IPC) and using Mas receptor (MasR) blockade, A779 or its vehicle, the renal vascular responses to angiotensin II (Ang II) administration in two-kidney-one-clip (2K1C) hypertensive rats were determined. METHODS: Thirty-seven 2K1C male Wistar rats with systolic blood pressure ≥150 mmHg were randomly divided into three groups; sham, IR, and IPC + IR. The animals in the sham group underwent surgical procedures except partial IR. The rats in the IR group underwent 45 min partial kidney ischemia, and the animals in the IPC + IR group underwent two 5 min cycles of partial kidney ischemia followed by 10 min reperfusion and partial kidney ischemia for 45 min. The renal vascular responses to graded Ang II (30, 100, 300, and 1000 ng kg-1.min-1) infusion using A779 or its vehicle were measured at constant renal perfusion pressure. RESULTS: Four weeks after 2K1C implementation, the intravenous infusion of graded Ang II resulted in dose-related increases in mean arterial pressure (MAP) (P dose < 0.0001) that was not different significantly between the groups. No significant differences were detected between the groups in renal blood flow (RBF) or renal vascular resistance (RVR) responses to Ang II infusion when MasR was not blocked. However, by MasR blockade, these responses were increased in IR and IPC + IR groups that were significantly different from the sham group (P < 0.05). For example, infusion of Ang II at dose 1000 ng kg-1.min-1 resulted in decreased RBF percentage change (RBF%) from the baseline to 17.5 ± 1.9%, 39.7 ± 3.8%, and 31.0 ± 3.4% in sham, IR, and IPC + IR, respectively. CONCLUSION: These data revealed the important role of MasR after partial kidney IR in the responses of RBF and RVR to Ang II administration in 2K1C hypertensive rats.

Investigating the association between rs6983267 polymorphism and susceptibility to gastrointestinal cancers in Iranian population.

Genome-wide association studies have revealed that some single nucleotide polymorphisms at 8q24, such as rs6983267, might be effective in susceptibility to various cancers in different populations. Therefore, rs6983267 might be useful as a marker for multiple cancers. In this study, we considered a population, including 478 gastrointestinal cancer cases from the Iranian population, to investigate the association between rs6983267 and susceptibility to gastrointestinal cancers. The samples were genotyped using the TaqMan real-time PCR method while 10% of them were also confirmed by sequencing. Higher frequency of G allele was associated with higher grades of tumors in esophageal cancer and the tumors located in the lower portion of the esophagus (OR 3.56; 95% CI 1.13-11.24; P = 0.03) and cardia (OR 5.24; 95% CI 1.26-21.83; P = 0.02), which both locations are involved in esophageal adenocarcinomas with poor prognosis. The results indicated that in the male subgroup, the rs6983267 GG genotype significantly enhanced the gastric cancer susceptibility (OR 4.76; 95% CI 1.57-14.45; P = 0.01). GG genotype also increased the risk of intestinal-type gastric cancer, located in non-cardia (OR 4.62; 95% CI 1.25-17.04; P = 0.02). Moreover, gastric cancer cases and controls with a family history of gastrointestinal tumors were mostly genotyped with the G allele (OR 3.61; 95% CI = 1.09-12.01; P = 0.04). There were no remarkable associations between rs6983267 and susceptibility to esophageal and colon cancers in the Iranian population. However, different genotypes of rs6983267 had significant correlations with tumor grade, cancer type, and family history of gastrointestinal cancers. Further investigations in a larger population and other ethnicities are required to confirm these results.