Angiogenesis is one hallmark of cancer. Vascular endothelial growth factor (VEGF) is a known inducer of angiogenesis. Many patients benefit from antiangiogenic therapies, which however have limitations. Although VEGF is overexpressed in most tumors, different VEGF isoforms with distinct angiogenic properties are produced through alternative splicing. In podocytes, the Wilms’ tumor suppressor 1 (WT1) suppresses the Serine/arginine-rich protein-specific splicing factor kinase (SRPK1), and indirectly Serine/arginine-rich splicing factor 1 (Srsf1) activity, and alters VEGF splicing. We analyzed VEGF isoforms, Wt1, Srpk1, and Srsf1 in normal and tumor endothelium. Wt1, Srpk1, Srsf1, and the angiogenic VEGF164a isoform were highly expressed in tumor endothelium compared to normal lung endothelium. Nuclear expression of Srsf1 was detectable in the endothelium of various tumor types, but not in healthy tissues. Inducible conditional vessel-specific knockout of Wt1 reduced Wt1, Srpk1, and Srsf1 expression in endothelial cells and induced a shift towards the antiangiogenic VEGF120 isoform. Wt1(−KTS) directly binds and activates both the promoters of Srpk1 and Srsf1 in endothelial cells. In conclusion, Wt1 activates Srpk1 and Srsf1 and induces expression of angiogenic VEGF isoforms in tumor endothelium.

The present study is designed to determine the effect of LCZ696 on DCM in rats and investigate the underlying mechanism involved. Diabetes was induced by feeding rats with a high-fat diet for six weeks following a single injection of STZ (30 mg/kg). Diabetic rats were divided into three groups (n = 10). LCZ696 and valsartan treatment was started two weeks after diabetic induction and continued for eight weeks. At the end of the treatment, serum and cardiac tissues were analyzed by RT-PCR, Western blot, and ELISA kits. LCZ696 and valsartan ameliorated DCM progression by inhibiting AGEs formation at activity levels; pro-apoptotic markers (BAX/Bcl2 ratio and caspase-3) in mRNA and protein expressions, the NF-κB at mRNA; and protein levels associated with the restoration of elevated proinflammatory cytokines such as the TNF-α, IL-6, and IL-1β at the activity level. Furthermore, LCZ696 and valsartan contribute to restoring the induction of ER stress parameters (GRP78, PERK, eIF2a, ATF4, and CHOP) at mRNA and protein levels. LCZ696 and valsartan attenuated DCM by inhibiting the myocardial inflammation, ER stress, and apoptosis through AGEs/NF-κB and PERK/CHOP signaling cascades. Collectively, the present results reveal that LCZ696 had a more protective solid effect against DCM than valsartan.

The study planned to estimate biological parameters linked to rheumatoid arthritis (RA) patients, detecting the influence of MTX and biotherapy treatments on these parameters and synthesizing methotrexate bovine serum albumin nanoparticles linked to folate (FA-MTX-BSA NPs) to reduce the overwhelming expression of inflammatory cytokines. Inflammatory parameters showed significant increases in newly diagnosed and MTX-receiving groups while no changes were observed in the biotherapy-maintained group. MTX-loaded BSA nanoparticles were fabricated by the desolvation method and further linked to activated folic acid to obtain FA-MTX-BSA NPs. FA-MTX-BSA NPs were successfully characterized within the nanoscale range using different screening techniques. FA-MTX-BSA NPs showed an in vitro release in a sustained manner. The potential of MTX, MTX-BSA NPs, and FA-MTX-BSA NPs in inducing cytokine level reduction was detected. Significant decreases in interleukin- 1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels were obtained in cultures treated with FA-MTX-BSA NPs compared to the untreated culture in a dose-dependent pattern. Furthermore, FA-MTX-BSA NPs comparing with MTX and MTX-BSA NPs exhibited a significant advanced effect in decreasing cytokines levels. Accordingly, the conjunction of BSA NPs and MTX linked to folate potentially reduced cytokines manifestation in RA.

Background and Objectives: The ABO blood group system is used to denote the presence of one, both, or neither of the A and B antigens on erythrocytes. In humans, this is the most important of the 43 different blood type (or group) classification systems currently recognized. Distribution of ABO and Rh among the Saudi population could affect many factors such as blood transfusion, prognosis, resistance and susceptibility to diseases. The impetus of this study was to develop an understanding of the distribution of the ABO and Rh types of healthy volunteer blood donors in the northern Asir region of Saudi Arabia, comparing the findings to similar studies. Understanding the frequency of different blood types in different populations is imperative. Subjects and Methods: This study was performed during the period of January 1, 2020, to December 31, 2020, using samples from 4167 voluntary subjects obtained from the blood bank of the King Abdullah Hospital, Bisha. Commercially provided anti-A, anti-B and anti-D antibodies were used for the standard blood grouping procedure. Results: The findings in this study showed that O was the most prominent ABO blood group, whereas AB was the least so. The frequency of the blood type A was the second highest, followed by the blood group B, whereas Rh positivity was more common than Rh negativity. Conclusion: O+ > A+ > B+ > O-> AB+> A-> B- > AB- was found to be the order of blood group frequency in the current study.

Iron deficiency anaemia is known to be one of the most common disorders that are associated with malnutrition. This study was conducted to form an understanding of the prevalence of Iron deficiency Anaemia (IDA) and evaluate its risk factors among the residents of the northern Asir Region, Saudi Arabia. Understanding the prevalence of IDA in different populations is important not only for therapeutic purposes but also for preventing the development of IDA in a given community. Moreover, this study was conducted to raise awareness about the significance of following iron-rich diet among high-risk groups such as women and children. This study collected data from 683 anaemic patients who are enrolled at the haematology unit in the Department of Internal Medicine at King Abdullah Hospital, Bisha Saudi Arabia. 398 participants who have IDA were included in this study where the collected data from the subjects included Age, gender, education, marital status, nationality, consanguinity, dietary habits and the clinical presentation of the participants. Our findings have shown that the prevalence of IDA among the participants is 58.27% where children under the age of 10 and females are the most affected individuals. Adults over 40, unmarried, and non-Saudis represented the second most affected portion of the subjects. IDA was prevalent among participants who shared the same ancestors and individuals with limited education. Moreover, participants did not consume sufficient iron and iron enhancing food or supplements. Inadequate iron intake is a major risk factor for anaemia. Low red fish and meat consumption contributed to the increase in ID. Findings highlight the need to raise awareness about the importance of a balanced diet and regular consumption of iron-containing food.