α-Glucosidase, butyrylcholinesterase and acetylcholinesterase inhibitory activities of phenolic compounds from Carthamus tinctorius L. flowers: In silico and in vitro studies.

Chemical investigation of Carthamus tinctorius L. flowers resulted in isolation of seven metabolites that were identified as; p-Hydroxybenzoic acid (1), trans hydroxy cinnamic acid (2), kaempferol-6-C-glucoside (3), astragalin (4), cartormin (5), kaempferol-3-O-rutinoside (6), and kaempferol-3-O-sophoroside (7). Virtual screening of the isolated compounds against human intestinal α-glucosidase, acetylcholinesterase, and butyrylcholinesterase was carried out. Additionally, the antioxidant activity of the bioactive compounds was assessed. Compounds 1 and 5 exhibited moderate binding affinities to acetylcholinesterase (binding energy -5.33 and -4.18 kcal/mol, respectively), compared to donepezil (-83.33kcal/mol). Compounds 1-7 demonstrated weak affinity to butyrylcholinesterase. Compounds 2 and 4 displayed moderate binding affinity to human intestinal α-glucosidase,compared to Acarbose (reference compound), meanwhile compound 2 exhibited lower affinity. Molecular dynamic studies revealed that compound 4 formed a stable complex with the binding site throughout a 100 ns simulation period. The in-vitro results were consistent with the virtual experimental results, as compounds 1 and 5 showed mild inhibitory effects on acetylcholinesterase (IC50s 150.6 and 168.7 µM, respectively). Compound 4 exhibited moderate α-glucosidase inhibition with an IC50 of 93.71 µM. The bioactive compounds also demonstrated notable antioxidant activity in ABTS [2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)], ORAC (oxygen radical-absorbance capacity), and metal chelation assays, suggesting their potential in improving dementia in Alzheimer's disease (AD) and mitigating hyperglycemia.

Dynamic interplay between corticosteroid treatment and the role of SRC-1 gene dysregulation in the progression of WHO-Grade 4 Astrocytoma.

BACKGROUND: Corticosteroid is commonly used before surgery to control cerebral oedema in brain tumours and is frequently continued throughout treatment. Its long-term effect of on the recurrence of WHO-Grade 4 astrocytoma remains controversial. The interaction between corticosteroid, SRC-1 gene and cytotoxic T-cells has never been investigated. METHODS: A retrospective cohort of 36 patients with WHO-Grade 4 astrocytoma were examined for CD8 + T-cell and SRC-1 gene expressions through IHC and qRT-PCR. The impact of corticosteroid on CD8+T-cells infiltration, SRC-1 expression, and tumour recurrence was analyzed. RESULTS: The mean patients age was 47-years, with a male to female ratio 1.2. About 78% [n = 28] of the cases showed reduced or no CD8+T-cell expression while 22% [n = 8] of cases have showed medium to high CD8+T-cell expression. SRC-1 gene was upregulated in 5 cases [14%] and 31 cases [86%] showed SRC-1 downregulation. The average of total days and doses of administered corticosteroid from the preoperative period to the postoperative period was at range of 14-106 days and 41-5028 mg, respectively. There was no significant statistical difference in RFI among tumours expressing high or low CD8+T-cells when corticosteroid was administered in recommended or exceeded doses [p-value = 0.640]. There was a significant statistical difference in RFI between CD8+T-Cell expression and SRC-1 gene dysregulation [p-value = 002]. Tumours with high CD8+T T-cell expression and SRC-1 gene downregulation had late recurrence. CONCLUSIONS: Corticosteroid treatment can directly affect the SRC-1 gene regulation but does not directly influence cytotoxic T-cells infiltration or tumor progression. However, SRC-1 gene downregulation can facilitate late tumor recurrence.

Team-based learning versus interactive lecture in achieving learning outcomes and improving clinical reasoning skills: a randomized crossover study.

BACKGROUND: This study aimed to investigate the impact of interactive lecture (IL) and team-based learning (TBL) on improving clinical reasoning skills (CRSs) and achieving learning outcomes (LO). Students' feedback was obtained about the strategies. METHODS: This study was carried out at the Faculty of Medicine in Rabigh, King Abdulaziz University, Jeddah, Saudi Arabia. Two modules, endocrinology, and emergency were selected. Students of each batch in both modules were divided into two arms. With a randomized crossover design, IL & TBL were used for two separate topics in each module. After each topic, a quiz in the form of well-structured MCQs was taken. A questionnaire was designed to obtain students' feedback. SPSS version 23 was used to analyse results. The difference between the mean values was calculated by Student's t-test. Feedback data is presented as frequency. P-value ≤ 0.05 was considered statistically significant. RESULTS: Learning outcomes were achieved by all groups in two modules, with both instructional strategies, IL and TBL. Students attempted >70% correct answers. However, in the emergency module, the groups with TBL as the instructional strategy performed better in quiz1 and quiz 2 (p = 0.026 and p = 0.016, respectively). Similarly, in the endocrinology module (3rd year), although the groups with TBL as the instructional strategy performed better in both quizzes, it was significant in quiz1 (p = 0.02). The difficulty indices of the clinical reasoning questions (CRQ) were used as the parameters for comparison. In the emergency module, group1, in quiz1, with TBL as an instructional strategy performed better in the CRQ (p = 0.017), while in quiz2, group2 with TBL as the instructional strategy performed better (p < 0.001). Group1 of the third-year students (endocrinology module) performed better in the CRQ in quiz 1 with TBL as an instructional strategy than group 2 with IL (p = 0.04). Mostly, students in both modules preferred TBL over IL, and especially they liked team application. Students perceived that TBL was a better strategy to learn CRS. CONCLUSIONS: Students achieved LOs and CRS better with TBL as an instructional strategy. They preferred TBL over IL. It is suggested to include TBL, or increase its percentage, in the curriculum.

Epigallocatechin gallate ameliorates tetrahydrochloride-induced liver toxicity in rats via inhibition of TGFß / p-ERK/p-Smad1/2 signaling, antioxidant, anti-inflammatory activity.

Chronic liver disease is a worldwide health problem. Carbon tetra hydrochloride is an environmental toxin which is regarded as highly toxic and a potential human carcinogen. It can cause liver damage through the generation of metabolites and production of free radicals. Green tea contains catechins such as Epigallocatechin gallate which has been found to reduce the inflammation, oxidative stress, and fibrosis in experimental animal models. Hence, it represents a good source to prevent or ameliorate several chronic diseases. Silymarin is extracted from milk thistle seeds and has been found to be an effective agent to reduce the oxidative stress and free radical production and thereby exert protective effects in chronic liver conditions. The present study was planned to keep in view the above-mentioned facts. We included thirty rats in our study and divided them into five groups, each having six rats and the study continued for 8 weeks. Group I received normal saline; Group 2 received i.p. CCl4 injections; Group 3 received CCl4 i.p. injection and Epigallocatechin gallate (EGCG) oral gavage, Group 4 received CCl4 i.p. injection and silymarin by oral gavage; and Group 5 received CCl4 i.p. injection and combined EGCG + silymarin by oral gavage. The study found that in group 2, CCl4 induced significant elevation of ALT and MDA and reduced GSH thereby signifying increased oxidative stress. CCl4 also significantly increased inflammatory (TNFα, NFκB, IL1ß, and TGFß) as well as fibrotic markers (p-ERK and p-Smad1/2 protein expression). EGCG and silymarin significantly reversed the previously mentioned parameters either alone or in combination; however, the effect was more pronounced in case of EGCG. We conclude that EGCG and silymarin possess liver protective effects through their antioxidant, anti-inflammatory, and antifibrotic action.

The Role of Liquid Biopsy in the Diagnosis and Prognosis of WHO Grade 4 Astrocytoma.

Liquid biopsy, as a non-invasive diagnostic tool, has recently gained significant attention in the field of oncology. It involves the analysis of various biomarkers present in bodily fluids, such as blood or cerebrospinal fluid, to provide information about the underlying cancer. In the case of WHO grade 4 astrocytomas, liquid biopsy has the potential to significantly impact the diagnosis and prognosis of this aggressive malignant brain tumor. By detecting specific genetic mutations, such as IDH1 or EGFR, and monitoring levels of circulating tumor DNA, liquid biopsy can aid in the early detection and monitoring of disease progression. This innovative approach is gradually being acknowledged as a less invasive and cost-effective procedure for cancer diagnosis and management to improve patient outcomes and quality of life. Various kinds of biomarkers circulating in cerebrospinal fluid (CSF), such as circulating tumor cells (CTC) and different types of nucleic acids like cell-free DNA (cfDNA), cell-free RNA (ctRNA), and microRNAs (miRNA), have been identified. These biomarkers, which require dependable detection methods, are comparatively simple to obtain and allow for repeated measurements, making them significantly superior for disease monitoring. This review aims to compare the latest liquid biopsy analysis tools for both CSF and plasma in the central nervous system.

The Cancer Driver Genes IDH1 and IDH2 and CD204 in WHO-Grade 4 Astrocytoma: Crosstalk Between Cancer Metabolism and Tumour Associated Macrophage Recruitment in Tumour Microenvironment.

Purpose: IDH1 and IDH2 are hotspot mutations commonly identified in WHO-grade 4 astrocytomas. Their association with TAMs has never been investigated. We aim to explore the crosstalk between the IDH1/2 mutation metabolic effect and TAMs in tumour microenvironment and how this relationship affects the tumour recurrence. Patients and Methods: The study included 20 samples of patients with WHO-grade 4 astrocytoma. The alteration hotspot in codon IDH1R132 and IDH2R172 was examined using direct sequencing. The protein expression of CD204 on TAM was detected through immunohistochemistry. Results: IDH1R132 and IDH2R172 were symmetrically identified as wildtype in 18/20 tumours (90%) and the remaining 2 tumours (10%) showed synonymous mutations on both codons. Tumours with IDH1/2-wildtype showed high expression of CD204+TAMs in 10 cases and low expression in 8 cases. Typical expression was seen equally in IDH1/2 mutant tumours. There was no significant association between IDH1/2 and CD204+TAM expression (p= 0.999). The association between the two groups was significantly observed among IDH-wildtype tumours (p=0.027). Highly expressed CD204 in IDH-wildtype tumours showed a median recurrence at 10 months compared to low CD204 expression, showed a median recurrence interval at 24 months. Conclusion: IDH1R132 or IDHR172 has the same impact on the classification and prognosis of WHO-grade 4 astrocytoma. There was no crosstalk between IDH1/2 metabolic effect and CD204+TAM. However, IDH-wildtype glioblastomas with dense CD204+TAM are associated with early recurrence. Because the sample size is small, a larger study is recommended to determine the impact of IDH1/2 on TAMs.

Association Between CD204-Expressed Tumor-Associated Macrophages and MGMT-Promoter Methylation in the Microenvironment of Grade 4 Astrocytomas.

Background: Tumor-associated macrophages (TAMs) are principal immune cells in glioma microenvironment which support tumor growth and proliferation. Our aim in this study was to assess the relationship between CD204-expressed TAMs and O6-methylguanine-DNA methyltransferase (MGMT)-promoter methylation in World Health Organization (WHO) grade 4 astrocytomas, and its impact on patient's clinical outcome. Methods: The expression of CD204 + TAMs was quantitively assessed on 45 samples of WHO grade 4 astrocytomas using immunohistochemistry. MGMT-promoter methylation was tested by methylation techniques. The relationship between TAMs, MGMT-promoter methylation, and recurrence-free interval (RFI) was statistically analyzed. Results: There were 10 cases (22.2%) with isocitrate dehydrogenase (IDH)-mutant grade 4 astrocytoma and 35 cases (77.8%) with IDH-wildtype glioblastoma. MGMT-promotor was methylated in 18 cases (40%), unmethylated in 15 cases (33%), and the remaining 12 cases showed no MGMT status because of nucleic acid degradations. The expression of CD204+ TAMs was high in 32 cases (71.7%) and low in 13 cases (28.8%). The relationship between IDH1 mutation and CD204+ TAM expression was insignificant (P = 0.93). However, the significant difference was found between MGMT methylation and CD204+ TAMs expression (P = 0.01), in which CD204+ TAMs were diffusely expressed in MGMT-methylated cases. There was no significant difference in RFI between CD204+ TAMs expression, MGMT-promoter methylation and treatment modalities. Conclusions: Grade 4 astrocytomas with diffusely expressed CD204+ TAMs are usually associated with MGMT-promoter methylation. Although this association is unclear, CD204+ TAMs may neutralize the effect of MGMT-DNA protein to loss its function, which contributes to tumor progression. This relationship had no significant impact on the patient's clinical outcome after different treatment modalities.

The Diagnostic Value of Pan-Trk Expression to Detect Neurotrophic Tyrosine Receptor Kinase (NTRK) Gene Fusion in CNS Tumours: A Study Using Next-Generation Sequencing Platform.

Background: Neurotrophic tyrosine receptor kinase (NTRK) fusion has been detected in rare types of CNS tumours, which can promote tumorigenesis. The efficacy of Trk inhibitor became a significant therapeutic interest. Our aim was to investigate whether Pan-Trk immunohistochemistry (IHC) is a reliable and efficient marker for detecting NTRK-fusion in different brain tumours. Methods: This study included 23 patients diagnosed with different types of CNS tumours. Testing for Pan-Trk IHC with monoclonal Ab (EPR17341) has been performed on all FFPE tissues. Parallelly, NTRK-rearrangements were tested using both DNA and RNA-based next-generation sequencing (NGS) assay using TruSight Onco500 platform. Results: The cohort included eight pilocytic astrocytomas, one oligodendroglioma, six IDHwildtype glioblastomas, four IDHmutant grade four astrocytomas, and one sample of each (astroblastoma, central neurocytoma, medulloblastoma, and liponeurocytoma). The mean age was 35 years; seven cases were in the paediatric age group, and 16 were adult. Pan-Trk expression was detected in 11 (47.8%) tumours, and 12 (52.1%) tumours showed no Pan-Trk expression. Nine Cases (82%) with different Pan-Trk expressions did not reveal NTRK-rearrangement. The other two positively expressed cases (liponeurocytoma and glioblastoma) were found to have NTRK2-fusions (SLC O 5A1-NTRK2, AGBL4-NTRK2, BEND5-NTRK2). All the 12 cases (100%) with no Pan-Trk expression have shown no NTRK-fusions. There was no statistically significant association between Pan-Trk expression and NTRK-fusion (p = 0.217). The detection of NTRK- fusions using NGS had high specificity over NTRK-fusion detection by using Pan-Trk IHC. Conclusion: Pan-Trk IHC is not a suitable tissue-efficient biomarker to screen for NTRK-fusions in CNS tumours, however RNA-based NGS sequencing should be used as an alternative method.

Immunolocalization of neurokinin 1 receptor in WHO grade 4 astrocytomas, oral squamous cell and urothelial carcinoma.

INTRODUCTION: Neurokinin-1 receptor (NK-1R) induces inflammatory reactions in peripheral tissues but its regulatory effects in target tissues is dependent on receptor signalling. Substance P (SP) has a high affinity for the NK-1R, to which it binds preferentially. We aimed to investigate the expression of NK-1R in World Health Organization (WHO) grade 4 astrocytomas as well as in oral squamous cell carcinoma (OSCC) and urothelial carcinoma, and its association with disease progression. MATERIAL AND METHODS: The study included tissue samples from 19 brain astrocytomas, 40 OSCCs and 10 urothelial carcinomas. NK-1R expression was quantitatively assessed in the tumour cells using immunohistochemistry. The relationship between NK-1R expression in astrocytomas and recurrence-free interval has been explored. RESULTS: The results showed that the NK-1R was intensely expressed in patients with WHO grade 4 astrocytoma, OSCC and urothelial carcinoma. However, cases clinically diagnosed as a low-grade cancer showed reduced NK-1R expression. CONCLUSIONS: NK-1R is overexpressed in all cases of WHO grade 4 astrocytoma, OSCC and urothelial carcinoma. The ubi-quitous presence of SP/NK-1R complex during tumour development and progression suggests a possible therapeutic key strategy to use NK-1R antagonist as an adjuvant therapy in the future.

Therapeutic applications of mesenchymal stroma cells in pediatric diseases: current aspects and future perspectives.

Mesenchymal stem cells or stroma cells (MSCs) were recently proven to play various therapeutic roles when used in clinical trials to control various inflammatory, neoplastic and immunologic diseases in children. Clinical trials show some promising results, particularly in diseases where conventional therapy is still ineffective. However, experimental studies sometimes show conflicting results. This review aims to assess the current therapeutic role of MSCs in the control of several pediatric diseases and elaborate on their future applications by reviewing published studies. A review of published studies on this subject based on Pubmed and Medical Subject Heading databases, with search for all relevant articles focusing on results of clinical trials to evaluate the clinical applications of MSCs. The review includes documentation of positive as well as negative applications of MSCs focused on pediatric diseases. MSCs have important immunosuppressive and antifibrotic effects that need to be employed to help patients with diseases for which no conventional management has proven to be effective. They may be also be used as an adjuvant to conventional therapeutic modalities to consolidate recovery. This review sheds light on the significance of the use of MSCs for the treatment of various pediatric diseases and focuses on promising applications. Most of the reported studies agree about the favorable use of MSCs in various diseases; however, more clinical trials, involving larger numbers of patients, need to be conducted in order to refine the outcome of the therapeutic methods and establish standardized protocols.

Undergraduate medical research in the Gulf Cooperation Council (GCC) countries: a descriptive study of the students' perspective.

OBJECTIVE: There is a lack of research-oriented physicians in several Arab countries and especially in Gulf region countries. In this context, it is important to explore medical students' perceptions and motivations towards research. The aim of the present study was to investigate research attitude, practices, and motivations among medical students from GCC countries. RESULTS: There were 228 students who participated in this study (male 88, females 140). Thirty-eight percent of the students were participating from Saudi Arabia, 20.6% from the UAE, 17.1% from Oman, 12.7% from Kuwait and 11.4% from Bahrain. Among participants, 43.0% had experience of funded research, and 53.1% had a contribution to research. The confidence of participants in their ability to interpret and to write a research paper was quite high (70.2%). The majority of the students (87.3%) believed that undergraduate students could conduct research and can present at conferences. Improving research skills, attaining research publication, and improvement in patient care were claimed as the top three motives for conducting research. The majority (75.0%) were compelled to research to facilitate their acceptance to a residency program and 63.6% due to compulsion for a research methodology course.

Unique features and risk factors of Helicobacter pylori infection at the main children's intermediate school in Rabigh, Saudi Arabia.

BACKGROUND: This study was conducted to determine characters and risk factors of Helicobacter pylori infection and its relationship with recurrent abdominal pain and other gastrointestinal symptoms at the main children's intermediate school in Rabigh, Saudi Arabia. METHODS: A cross-sectional study was conducted at a boys' intermediate school. A questionnaire for the gastrointestinal (GI) symptoms and relevant personal and socioeconomic risk factors related to H. pylori infection was distributed followed by H. pylori IgG antibody assay and 14C urea breath test to detect active infection. RESULTS: H. pylori was diagnosed by positive urea breath test in 51.5 % of students. H. pylori infection was symptomatic with at least one upper GI symptom in 89.7 % of infected students which was higher than symptomatic cases reported in any other study. H. pylori-infected students had significantly more association with the presence of any upper GI symptom (p < 0.001), recurrent abdominal pain (p < 0.001), anorexia (p < 0.001), nausea (p < 0.026), family history of peptic disease (p < 0.001), drinking desalinated municipal water (p < 0.001), lower income (p = 0.02), and eating outside home (p = 0.003) than uninfected students. Logistic regression analysis showed that the most significant predictors of H. pylori infection were presence of any upper GI symptom (OR 5.3, 95 % CI 2.32-15.71), family history of peptic disease (OR 2.2, 95 % CI 1.11-3.9), and drinking desalinated municipal water (OR 2.1, 95 % CI 1.09-3.2). CONCLUSIONS: This study presented unique features and risk factors of H. pylori infection in 12-15-year-old Saudi boys in Rabigh, and mainly supported the role of H. pylori in causing recurrent abdominal pain.

Treatment adherence and quality of life outcomes in patients with sickle cell disease.

OBJECTIVE: To assess the health-related quality of life (HRQL) of patients with sickle cell disease (SCD) and to measure the impact of treatment adherence on disease complication, severity, crisis, and outcome. METHODS: This was a cross-sectional study on patients with SCD who attended the Hematology Clinic at King Abdulaziz University Hospital from January 2009 to December 2011. We measured the primary outcome of health-related quality of life (HRQL) using the World Health Organization quality of life assessment instrument (WHOQOL-BREF). Data were collected and analyzed using the Statistical Package for Social Sciences. Analysis of HRQL was carried out along the scoring of WHOQOL-BREF. RESULTS: One hundred fifteen patients completed the questionnaire. Eighty-seven patients (75.7%) had severe SCD, while 28 (24.3%) had mild disease. Patients with severe disease had a low HRQL (p=0.002). Pain episodes were the main cause of hospitalization (n=59; 51.3%). Thirty-six of patients (31.3%) who had pain episodes were on regular narcotics and had low HRQL scores (p=0.0001). The HRQL scores significantly decreased as pain levels increased. Patients with delayed treatment or those who were not adherent to treatment showed worse HRQL scores (p=0.001). CONCLUSION: Treatment adherence and early intervention in SCD improved HRQL outcomes.

Effect of sequential versus standard Helicobacter pylori eradication therapy on the associated iron deficiency anemia in children.

OBJECTIVES: Helicobacter pylori infection may be associated with low iron stores and iron deficiency anemia. Eradication of infection by the standard 10-day therapy (a proton pump inhibitor [PPI], clarithromycin and amoxicillin; each given orally, twice daily) is decreasing. The sequential 10-day therapy (a PPI and amoxicillin; each given orally twice daily for 5 days; followed by a PPI, clarithromycin and tinidazole; each given orally twice daily for another 5 days) may achieve higher eradication rates. This study was designed to investigate, which eradication regimen; sequential or standard; more effectively improves the associated iron status and iron deficiency in children. MATERIALS AND METHODS: Children (12-15 years) with H. pylori active infection (positive H. pylori immunoglobulin G and urea breath test [UBT]) were subjected to measurement of serum ferritin and then randomized into two groups to receive standard and sequential eradication therapy. Six weeks after completing therapy, UBT was performed to check eradication and serum ferritin was measured to estimate affection by therapy. Statistical Package for Social Sciences (SPSS, IBM, NY, USA) was used for analysis. RESULTS: H. pylori eradication rates of sequential versus standard therapy were non-significantly different. Serum ferritin non-significantly differed between the two therapy groups and in the same group before and after treatment. CONCLUSIONS: There is no significant difference in H. pylori eradication rates between sequential and standard therapies in children. Moreover, no significant relationship was found between eradication therapy and serum ferritin. Further studies enrolling more markers of iron deficiency are required to precisely assess this relationship.