Brain cancer remains among the most lethal malignancies worldwide, with approximately 321,476 new cases and 248,305 deaths reported globally in 2022. The treatment of malignant brain tumors presents substantial clinical challenges, primarily due to their resistance to standard therapeutic approaches. Despite decades of intensive research, effective treatment strategies for brain cancer are still lacking. Nuclear receptors (NRs), a superfamily of ligand-activated transcription factors, regulate a broad range of physiological processes including metabolism, immunity, stress response, reproduction, and cellular differentiation. Increasing evidence highlights the involvement of NRs in oncogenesis, with several members demonstrating altered expression and function in brain tumors. Aberrations in NR signaling, encompassing receptors such as androgen receptors, estrogen receptors, estrogen-related receptors, glucocorticoid receptors, NR subfamily 4 group A, NR subfamily 1 group D member 2, NR subfamily 5 group A member 2, NR subfamily 2 group C member 2, liver X receptors, peroxisome-proliferator activated receptors, progesterone receptors, retinoic acid receptors, NR subfamily 2 group E member 1, thyroid hormone receptors, vitamin D receptors, and retinoid X receptors, have been implicated in promoting hallmark malignant phenotypes, including enhanced survival, proliferation, invasion, migration, metastasis, and resistance to therapy. This review aims to explore the roles of key NRs in brain cancer, with an emphasis on their prognostic significance, and to evaluate the therapeutic potential of targeting these receptors using selective agonists or antagonists.
Humans ; Brain Neoplasms/drug therapy* ; Receptors, Cytoplasmic and Nuclear/metabolism* ; Animals ; Signal Transduction/physiology*

Background and Objective: Convalescent plasma therapy (CPT) may reduce the risk of disease progression among patients with COVID-19. This study was undertaken to evaluate the efficacy and safety of CPT in preventing ICU admission among hospitalized COVID-19 patients. Methods: In this open-label randomized controlled trial, we randomly assigned hospitalized adult patients with COVID-19 in a 1:1 ratio to receive convalescent plasma as an adjunct to standard of care or standard of care alone. The primary endpoint was ICU admission within first 28 days of enrolment. Primary safety endpoints include rapid deterioration of respiratory or clinical status within four hours of convalescent plasma transfusion and cumulative incidence of serious adverse events during the study period including transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), severe allergic reactions, and transfusion-related infections. Results: A total of 22 patients were assigned to receive convalescent plasma as an adjunct to standard of care and 22 to receive standard of care alone. The median time from onset of COVID-19 symptoms to study enrolment was eight days (IQR, 4 to 10). Two patients (9.1%) in the CPT group and one patient (4.5%) in the control group were admitted to the ICU. The primary outcome measure, ICU admission, was not different between the two groups (q-value >0.9). No patient who received convalescent plasma had rapid deterioration of respiratory/clinical status within four hours of transfusion and none developed TRALI, TACO, anaphylaxis, severe allergic reactions, or transfusion-related infections. There was also no significant difference in the secondary outcomes of 28-day mortality (two patients in the CPT group and none in the control group, q-value >0.90), dialysis-free days, vasopressor-free days, and ICU-free days. Conclusions Among hospitalized COVID-19 patients, no significant differences were observed in the need for ICU admission between patients given CPT as adjunct to standard of care and those who received standard of care alone. Interpretation is limited by early termination of the trial which may have been underpowered to detect a clinically important difference.
COVID-19 ; COVID-19 Serotherapy

OBJECTIVE: To determine whether resveratrol (Res) can correct osteoporosis induced in a rat model of male hypogonadism. METHODS: Thirty-two rats were randomly divided into 4 groups, 8 in each group; 1) a control sham group: underwent a similar surgical procedure for induction of orchiectomy (ORCD) without ligation of any arteries or veins or removal of the testis and epididymis; 2) a control + Res-treated group (Con+Res): underwent sham surgery similar to the control, but was then treated with Res, as described below; 3) an ORCD-induced group: bilateral ORCD surgery as described above, and 4) a ORCD+Res-treated group: bilateral ORCD surgery followed by Res treatment. Res treatment began 4 weeks after ORCD and continued for 12 weeks. After 12 weeks, bone mineral density (BMD) and bone mineral content (BMC) were measured in the tibia and femur of each rat's right hind leg. Blood levels of bone turnover indicators such as deoxypyridinoline (Dpd), N-telopeptide of type I collagen (NTX I), alkaline phosphatase (ALP), and osteocalcin (OC), as well as receptor activator of nuclear factor kappa B (RANK) and osteoprotegerin (OPG) were assessed. RESULTS: ORCD significantly decreased BMD (P<0.01) and significantly increased bone resorption, manifested by increased RANK. In addition, it inhibited serum levels of OPG and OC. Res treatment after ORCD effectively increased serum levels of bone formation markers such as OPG and OC, compared with testisectomized rats (P<0.05). CONCLUSION Res could ameliorate bone loss induced by male hypogonadism, possible via restoration of the normal balance between RANK and OPG.
Rats ; Male ; Animals ; Bone Density ; Resveratrol/pharmacology* ; Osteoporosis ; Osteoprotegerin/pharmacology* ; Bone Remodeling ; Hypogonadism ; RANK Ligand/pharmacology*

Introduction: Lack of adherence to a strict gluten-free diet (GFD) is the main reason for poorly controlled disease in patients with coeliac disease (CD). This study aimed to assess the association between knowledge of CD and its medical diet to the adherence of GFD among adult patients with CD. Methods: A cross-sectional study was carried out with a total of 90 adult patients with CD (aged between 18-65 years). The data collecting instruments were a combination of four questionnaires as follows: assessment of knowledge of coeliac disease (AKCD), gluten-free diet knowledge scale (GFD-KS), coeliac disease adherence test (CDAT), and questions on potential factors influencing GFD adherence among patients. Results: An average knowledge score of five points out of seven was obtained from 46 participants (51%). Mean score for knowledge on gluten-free diet was seven points out of 17 in 59 participants (65%). Adequate adherence to GFD was observed in 56% of the participants. No association was found between knowledge of CD and GFD to the adherence of GFD (p>0.050). Participants who had higher adherence scores were discussing GFD with a specialist, obtaining educational materials, had enhanced symptoms associated with CD, and did not complain about the taste of GFD (p<0.050). Conclusion: Patients with CD has adequate knowledge of CD and adherence of GFD. No association was found between the knowledge of CD and GFD to the adherence of GFD. Further research might explore other potential factors influencing the adherence to GFD.

Purinergic P2Y Receptor Antagonists ; Consensus ; Cardiovascular System ; Cardiology ; Asia

We aimed at determination of acaricidal, larvacidal, and repellent activities of green synthesized silver nanoparticles (SNP) against Hyalomma dromedarii as one of the most common ticks in camels. SNP were green synthesized by reducing Lupinus albus extract through the precipitation technique. The acaricidal, larvicidal, and repellent activity of SNP against H. dromedarii was studied through the adult immersion test (AIT), the larval packet test (LPT), the vertical movement behavior of tick’s larvae method, anti-acetylcholinesterase (AChE) activity, and oxidative enzyme activity. The green synthesized SNP displayed a spherical form with a size ranging from 25–90 nm; whereas the most distribution of particles size was reported at 50-65 nm. SNP dose-dependently (p<0.001) increased the mortality rate of H. dromedarii adult; whereas at 16 and 32 µg/mL completely killed the adult females. Treatment of exposure of H. dromedarii adult to SNP markedly (p<0.001) declined the mean number, weight, and hatchability of eggs. Treatment of H. dromedarii larvae with SNP reduced the viability rate of larvae with the LC50 and LC90 values of 3.1 and 6.9 µg/mL, respectively. Exposure of H. dromedarii larvae to SNP, especially at ½ LC50 and LC50, markedly (p<0.001) increased the oxidative stress and declined the level of antioxidant enzymes in H. dromedarii larvae; whereas, markedly suppressed the AChE activity of the larvae stage of H. dromedarii in comparison to the control group. These results showed that SNP green synthesized by L. albus extract had promising acaricidal, larvicidal and repellent activity against H. dromedarii adults and larvae as a dose-dependent response. SNP also considrably decreased the level of acetylcholinesterase and antioxidant activity and also provokes oxidative stress in H. dromedarii larvae. However, more investigation must be designed to clear the accurate mechanisms and the efficacy of SNP in practical use.

A series of new 2,5-disubstituted-1,3,4-oxadiazole derivatives (5a-j and 6a-j) have been designed and synthesized in four-steps. Sixteen compounds among the twenty compounds are reported for the first time. The compounds were characterized and confirmed by the FTIR, 1D- and 2D-NMR and HRMS analyses, and were tested against Mycobacterium smegmatis and Mycobacterium tuberculosis H37Ra. Compound 5d was the most active against M. smegmatis with MIC value of 25 µM, and exhibited cidal activity with MBC of 68 µM, respectively. The time-kill assay showed the good killing rate at 77% with the combination of isoniazid (INH). In addition, checkboard assay confirmed the interaction of compound 5d was categorised as additive. Docking simulation has been performed to position 5d into the pantothenate synthetase active site with binding free energy value –8.6 kcal mol-1. It also occupied the same active site as that of standard native ligand with similar interactions, which clearly indicate their potential as pantothenate synthetase inhibitor.

Background: The World Health Organization identified mental health as "essential to human health" in its plan for preventing, treating, and conquering mental health diseases. It is believed that anxiety and depression, according to the American Psychological Association (APA), are both emotional responses that cause a comparable cluster of characteristics, such as sleep problems, exhaustion, muscular tightness, and restlessness. The study aimed to assess the prevalence of depression, anxiety, and stress among high school students in Jeddah city. Methods: A cross-sectional study; was carried out at selected secondary schools in Jeddah city from different districts (North-South-West-East); during the period from January 2022 to May 2022. The population sample for this study included female secondary students. Sample calculation was done by Stephen Thompson formula. Results: It was found that more than half [57.1%] of the participants are free from depression; [53.4%] are free from anxiety; while [81.0%] are not suffering from stress. There was a statistically significant correlation between depression and stress among students and their academic achievement. Moreover, there was a significant association between anxiety among students and their parent's status. Conclusion School students' stress, anxiety, and depression prevalence are relatively high. Several variables were significantly associated with secondary school students suffering from stress, anxiety, and depression, such as academic achievement, family income, and marital status of students and their parents.

Plants are alternative source of natural medicines due to secondary active metabolites. Fagonia cretica extracts and Gradient High-Pressure Liquid Chromatography fractionations were checked against multidrug-resistant gastrointestinal pathogens including, Salmonella typhi, Escherichia coli and Shigella flexneri. ESI-MS/MS analysis of bioactive HPLC fractions was performed to elucidate antibacterial compounds. F. cretica extracts exhibited potential antibacterial activity. Twenty-four (24) HPLC fractions were obtained from methanol, ethanol and aqueous extracts of F. cretica. Eighteen (18) fractions showed antibacterial activity, while no activity was observed by the remaining six (6) fractions. HPLC fractions, F1 (25g ± 0.20 mm) and F2 (15f ± 0.12 mm) of aqueous extract exhibited activity against multidrug resistant GI pathogens. Gallic acid, quinic acid, cyclo-l-leu-l-pro, vidalenolone, liquirtigenin, rosmarinic acid and cerebronic acid were identified in F1 fraction of aqueous extract, while succinic acid, cyclo (l-Leul-Pro) and liquirtigenin were identified in F2 fraction of aqueous extract through ESI-MS/MS analysis. F. cretica extracts and HPLC fractions showed potential activity against MDR GI pathogens. Vidalenolone, Cyclo-1-leu-1-pro and Cerebronic acid are first time reported in F. cretica. Further characterization of bioactive compounds from F. cretica may be helpful to elucidate antibacterial therapeutic molecules.

Stress and depression among physicians are recognized as important problems because of the potential risks they impose on individual health and medical care. This study aims to assess level of stress and depression and associated factors among family medicine residents in Al-Madinah, Saudi Arabia. Methods: This cross-sectional study was conducted among 75 residents in the family medicine residency programs in Al-Madinah. Stress and depression were assessed by using the stress and depression subscales of the validated Depression, Anxiety and Stress Scale-21 item (DASS-21). Sources of stress were assessed by 22 items. Results: Most participants had stress (57.3%) and depression (53.3%). Stress was associated with work overload (P=0.032), work demands affect personal/home life (P<0.001), inability to participate in decision making (P=0.026) and inability to make full use of skills and abilities (P=0.019). Depression was associated with ‘work demands affect personal/home life’ (P<0.001). Conclusion: The prevalence of stress and depression among family resident doctors was high. Establishing a residency counseling office is suggested to deal with the resident's problems in a way that supports their needs and leads to the best working environment.