حيدر شهيد جواد قسام

Ischemia-reperfusion injury (IRI) can be defined as changes in the functions and structures of the tissues resulting from the restoration of blood after a period of ischemia. This study aimed to assess the potential protective effect of Fimasartan (angiotensin receptor antagonist) in the bilateral renal IRI in male rats through its potential effect on renal functions, modulation of the inflammatory cascade, oxidative stress, and apoptotic effect. The animals were equally assigned into four groups. The sham (negative control) group was exposed to surgical conditions without induction of IRI. The control group was exposed to ischemia by occluding the renal pedicles by clamps for 30 min, followed by restoration of blood for 2h. The vehicle-treated group received dimethyl sulfoxide (DMSO) by intraperitoneal injection (IP) 30 minutes before clamping. Fimasartan-treated group: rats pretreated with Fimasartan a dose of 3 mg/kg IP; this was half hour before occluding the renal pedicles. Animals were then exposed to 30 min ischemia (clamping the renal pedicles) followed by 2h reperfusion by releasing the clamps. Blood samples were collected to examine the levels of serum urea and creatinine. Renal tissue was used to measure the levels of cytokines (TNFα, IL-6) and total antioxidant capacity (TAC). Immunohistochemistry was used to assess the levels of Bax, caspase 3, and Bcl-2. Histopathological analyses were performed to detect the parenchymal injury. The present study shows that pretreatment with Fimasartan improves kidney function through its effects on oxidative stress, cytokines, and apoptotic markers. Keywords: Fimasartan, renal ischemia, Bcl-2, caspase 3, oxidative stress

Ischemia-reperfusion injury (IRI) can be defined as changes in the functions and structures of the tissues resulting from the restoration of blood after a period of ischemia. This study aimed to assess the potential protective effect of Fimasartan (angiotensin receptor antagonist) in the bilateral renal IRI in male rats through its potential effect on renal functions, modulation of the inflammatory cascade, oxidative stress, and apoptotic effect. The animals were equally assigned into four groups. The sham (negative control) group was exposed to surgical conditions without induction of IRI. The control group was exposed to ischemia by occluding the renal pedicles by clamps for 30 min, followed by restoration of blood for 2h. The vehicle-treated group received dimethyl sulfoxide (DMSO) by intraperitoneal injection (IP) 30 minutes before clamping. Fimasartan-treated group: rats pretreated with Fimasartan a dose of 3 mg/kg IP; this was half hour before occluding the renal pedicles. Animals were then exposed to 30 min ischemia (clamping the renal pedicles) followed by 2h reperfusion by releasing the clamps. Blood samples were collected to examine the levels of serum urea and creatinine. Renal tissue was used to measure the levels of cytokines (TNFα, IL-6) and total antioxidant capacity (TAC). Immunohistochemistry was used to assess the levels of Bax, caspase 3, and Bcl-2. Histopathological analyses were performed to detect the parenchymal injury. The present study shows that pretreatment with Fimasartan improves kidney function through its effects on oxidative stress, cytokines, and apoptotic markers. Keywords: Fimasartan, renal ischemia, Bcl-2, caspase 3, oxidative stress

Acute kidney injury (AKI) with all advances in nursing measures and therapeutic strategies, such as kidney transplantation and dialysis, mortality rate of patients with AKI is very high in past 30 years.

Abstract The structurally related, but distinct neuropeptides, neuromedin U (NmU) and neuromedin S (NmS) are ligands of two G protein-coupled NmU receptors (NMU1 and NMU2). Hypothalamic NMU2 regulates feeding behavior and energy expenditure and has therapeutic potential as an anti-obesity target, making an understanding of its signaling and regulation of particular interest. NMU2 binds both NmU and NmS with high affinity, resulting in receptor-ligand co-internalization. We have investigated whether receptor trafficking events post-internalization are biased by the ligand bound and can therefore influence signaling function. Using recombinant cell lines expressing human NMU2, we demonstrate that acute Ca2+ signaling responses to NmU or NmS are indistinguishable and that restoration of responsiveness (resensitization) requires receptor internalization and endosomal acidification. The rate of NMU2 resensitization is faster following NmU compared with NmS exposure, but is similar if endothelin-converting enzyme-1 activity is inhibited or knocked down. Although acute activation of extracellular signal-regulated kinase (ERK) is also similar, activation by NMU2 is longer lasting if NmS is the ligand. Furthermore, when cells are briefly challenged before removal of free, but not receptor-bound ligand, activation of ERK and p38 mitogen-activated protein kinase by NmS is more sustained. However, only NmU responses are potentiated and extended by endothelin-converting enzyme-1 inhibition. These data indicate that differential intracellular ligand processing produces different signaling and receptor resensitization profiles and add to the findings of other studies demonstrating that intracellular ligand processing can shape receptor behavior and signal transduction.

Intestinal mobility disorders are either hypo or hypermotility conditions that affect the gastrointestinal tract due to smooth muscle or neuronal disorders. Betalains are good candidates to be evaluated for their intestinal modulating properties since they may have a higher safety index and pleiotropic efficacy. In this small sample, clinical trials (N = 26 cases of motility disorders), fasting, and betalains intake cases of motility disorders had been measured for their electro enterography EEnG at 8:00 am. Betalains intake cases were given oral doses of 12 mg/kg betalains extract 30 minutes before measurements. A biosignal interface was used (UNO, Italy) and the driver was installed within the Simulink R2021b block with the use of a lowpass filter to cancel ECG wave interference. The participant's privacy, autonomy, and information about the use of this habitually used beetroot extract were insured and verbally explained regarding the purpose of the study, the method, and the time of analysis. The results have clearly shown that the oral administration of the aqueous extract of betalains achieved mild antispasmodic effects in cases with intestinal hypermotility disorders by decreasing the maximum force of contraction as had been indicated by EEnG reduction in the mean amplitude difference from 1.25 micV to 1.07 micV. Moreover, betalains caused EEnG frequency to decline from 21.5 MHz to 18.5 MHz. These effects were mild although statistically significant (P = 0.04). The oral dose of 12 mg/kg of betalains aqueous extract showed mild but significant intestinal relaxing effects in patients with intestinal hypermotility disorders.

Background Sepsis is a prevalent ailment that significantly affects hospitalized individuals around the globe. It is characterized by uncontrolled inflammatory responses resulting in organ injury and leading to high morbidity and mortality. The liver, a vital organ, is affected by sepsis, resulting in liver dysfunction. Dimethyl fumarate (DMF), which is approved for the treatment of multiple sclerosis, has anti-inflammatory and neuroprotective properties through the inhibition of multiple inflammatory mediators. Hence, the present study aimed to assess the hepatoprotective potential of DMF against sepsis. Methods Four groups of mice (6 animals per group) were divided into a sham group, which was subjected to only anaesthesia and a midline abdominal incision; the cecal ligation and puncture (CLP) group was anaesthetized and underwent an abdominal incision followed by the ligation of the cecum under the ileocecal valve and perforation twice with a needle; the vehicle group was given a solvent of DMF 1 h before the CLP, and the CLP group received 50 mg/kg of DMF via intraperitoneal (ip) injection 1 h before CLP. Following the procedure (24 h post-CLP), the mice were given unrestricted access to food and drink throughout the day. Serum was used to measure the levels of angiopoietin 2, AST and ALT. Enzyme-linked immunosorbent assay (ELISA) was used to investigate the levels of TNF-α, IL-6, MIF, ICAM-1, F2-isoprostanes, VEGF, and caspase 11 in liver tissues. To evaluate the degree of liver damage, a biopsy of the liver was performed. Results The results revealed that mice exposed to CLP had high levels of AST and ALT in comparison with sham mice. Furthermore, levels of TNF-α, IL-6, MIF, ICAM-1, F2-isoprostanes, VEGF, and caspase 11 in liver tissues were also notably elevated as compared with sham mice. The levels of these parameters were significantly decreased in septic mice pre-treated with DMF. Mice with CLP showed a severe degree of liver damage as compared with sham mice. DMF pre-treatment mitigated liver injury. Conclusion This study suggests that DMF has hepatoprotective effects on septic mice via the modulation of inflammation, adhesion molecules, angiopoietin 2 and pyroptosis.