Targeting Cancer Hallmarks Using Selected Food Bioactive Compounds: Potentials for Preventive and Therapeutic Strategies.

Cancer continues to be a prominent issue in healthcare systems, resulting in approximately 9.9 million fatalities in 2020. It is the second most common cause of death after cardiovascular diseases. Although there are difficulties in treating cancer at both the genetic and phenotypic levels, many cancer patients seek supplementary and alternative medicines to cope with their illness, relieve symptoms, and reduce the side effects of cytotoxic drug therapy. Consequently, there is an increasing emphasis on studying natural products that have the potential to prevent or treat cancer. Cancer cells depend on multiple hallmarks to secure survival. These hallmarks include sustained proliferation, apoptosis inactivation, stimulation of angiogenesis, immune evasion, and altered metabolism. Several natural products from food were reported to target multiple cancer hallmarks and can be used as adjuvant interventions to augment conventional therapies. This review summarizes the main active ingredients in food that have anticancer activities with a comprehensive discussion of the mechanisms of action. Thymoquinone, allicin, resveratrol, parthenolide, Epigallocatechin gallate, and piperine are promising anticancer bioactive ingredients in food. Natural products discussed in this review provide a solid ground for researchers to provide effective anticancer functional food.

Natural Products and Altered Metabolism in Cancer: Therapeutic Targets and Mechanisms of Action.

Cancer is characterized by uncontrolled cell proliferation and the dysregulation of numerous biological functions, including metabolism. Because of the potential implications of targeted therapies, the metabolic alterations seen in cancer cells, such as the Warburg effect and disruptions in lipid and amino acid metabolism, have gained attention in cancer research. In this review, we delve into recent research examining the influence of natural products on altered cancer metabolism. Natural products were selected based on their ability to target cancer's altered metabolism. We identified the targets and explored the mechanisms of action of these natural products in influencing cellular energetics. Studies discussed in this review provide a solid ground for researchers to consider natural products in cancer treatment alone and in combination with conventional anticancer therapies.

Knowledge, awareness and attitude towards breast cancer: Risk factors, signs and screening among Health and Allied students: A prospective study.

Introduction: Breast cancer (BC) is the second most common cancer in Saudi women. Therefore, understanding BC and its related risk factors, symptoms, and screening is critical for early detection and intervention. The current study was meant to explore the knowledge, awareness, and attitude (KAA) gap in BC: risk factors, symptoms, and screening. Material and Methods: This cross-sectional investigation was carried out with Health Professions Students (HPS) using a predesigned and validated study questionnaire to examine HPS knowledge and attitudes concerning BC and associated risk factors, symptoms, and screening. Results: A total of 277 female students responded to the survey. The frequency of correct answers for the BC knowledge questions varied from the lowest of 27.8% to the highest of 88.8%, with only 5 out of 15 questions (33.3%) answered correctly by more than 60% of the participants, displaying poor knowledge and awareness of BC. A majority (>60%) of the participants identified only 7 of the 18 risk factors of BC correctly, whereas 11 of the 13 early warning signs of BC were identified correctly by the majority (>60%) of the participants. Among the participants, only 26.4% were aware of the breast cancer screening center, but 94.6% of them agreed that early detection of breast cancer is important and 82.7% agreed to participate in the screening program if offered. Conclusion: Participants' knowledge and awareness of BC were found to be relatively low; however, their attitudes towards BC screening were positive. As a result, it is critical to develop effective education programs, curricular activities, and awareness campaigns to address the lack of awareness of BC and to have an appropriate response to screening to reduce disease burden.

The Prevalence of Anxiety Among Children in Saudi Arabia During the COVID-19 Pandemic: A Cross-Sectional Study.

BACKGROUND: The year 2021 was a year that can be perceived as a stressful event given the considerable lifestyle changes that have occurred worldwide due to the pandemic. Several studies have investigated the psychological impact on people during this time period. However, only a few of them have investigated the impact on young children in Saudi Arabia (SA) specifically. Therefore, this study aimed to investigate the prevalence of anxiety in children living in Jeddah, Saudi Arabia. METHODS: This is a cross-sectional study that included the parents of 388 children aged 6-9 years living in Jeddah, Saudi Arabia. It was conducted from June to November 2021. The parents completed an electronic survey that included the Arabic version of the Spence Children's Anxiety Scale. The data were analyzed using John's Macintosh Project (JMP) software version 10.0 (SAS Institute Inc., Cary, NC). RESULTS: A total of 388 responses were collected. The data revealed that 37 (9.5%) participants experienced anxiety. Furthermore, the prevalence of anxiety was higher among females (5.15%) as compared to males (4.38%), but the difference was not statistically significant. CONCLUSION: These findings highlight the importance of recognizing the psychological burden in young populations and emphasize the importance of taking children's well-being into account.

Prevalence of Clostridium Difficile Infection (CDI) among Inflammatory Bowel Disease (IBD) Patients in Comparison to Non-IBD Patients in King Abdulaziz Medical City in Jeddah.

Background: The prevalence of Clostridium difficile infection (CDI) as a common complication among inflammatory bowel disease (IBD) has been reported to increase worldwide and has been associated with a poor IBD outcome. Objectives: In this study, our aim was to report on the prevalence of CDI among IBD vs. non-IBD patients in King Abdulaziz Medical City (KAMC). Methods: This retrospective descriptive study was carried out between 2016 and 2020. Data of 89 patients reported with CDI in KAMC were analyzed for demographics and correlations between various characteristics such as BMI, personal/family history of IBD, infection with CDI, diagnosis, method of diagnosis, and treatment modalities. Results: Of the total 89 CDI patients, 59 (66.3%) were adults and 30 (33.7%) were pediatric, of which 36 (40.4%) were females and 53 (59.6%) were males. PCR was the main method of choice for the diagnosis of CDI (89.9%) followed by a positive-culture result (10.0%). Seventy-eight (87.6%) CDI patients were found to be immunocompromised, with two patients diagnosed with IBDs, one with UC, and one with CD. The recurrence rate was 38.4 (30 patients) among the immunocompromised group in comparison to 27.2 (3 patients) in the immunocompetent group (p=0.584). Conclusion: In this study, we found that adults were more prone to CDI infection, especially within hospital settings, and most of the CDI infections occurred in immunocompromised individuals, with cancer as the most common cause of it.

Design, Synthesis, and Biological Evaluation of New Potential Unusual Modified Anticancer Immunomodulators for Possible Non-Teratogenic Quinazoline-Based Thalidomide Analogs.

Sixteen new thalidomide analogs were synthesized. The new candidates showed potent in vitro antiproliferative activities against three human cancer cell lines, namely hepatocellular carcinoma (HepG-2), prostate cancer (PC3), and breast cancer (MCF-7). It was found that compounds XII, XIIIa, XIIIb, XIIIc, XIIId, XIVa, XIVb, and XIVc showed IC50 values ranging from 2.03 to 13.39 µg/mL, exhibiting higher activities than thalidomide against all tested cancer cell lines. Compound XIIIa was the most potent candidate, with an IC50 of 2.03 ± 0.11, 2.51 ± 0.2, and 0.82 ± 0.02 µg/mL compared to 11.26 ± 0.54, 14.58 ± 0.57, and 16.87 ± 0.7 µg/mL for thalidomide against HepG-2, PC3, and MCF-7 cells, respectively. Furthermore, compound XIVc reduced the expression of NFκB P65 levels in HepG-2 cells from 278.1 pg/mL to 63.1 pg/mL compared to 110.5 pg/mL for thalidomide. Moreover, compound XIVc induced an eightfold increase in caspase-8 levels with a simultaneous decrease in TNF-α and VEGF levels in HepG-2 cells. Additionally, compound XIVc induced apoptosis and cell cycle arrest. Our results reveal that the new candidates are potential anticancer candidates, particularly XIIIa and XIVc. Consequently, they should be considered for further evaluation for the development of new anticancer drugs.

Thymoquinone Ameliorates Carfilzomib-Induced Renal Impairment by Modulating Oxidative Stress Markers, Inflammatory/Apoptotic Mediators, and Augmenting Nrf2 in Rats.

Chemotherapy-induced kidney damage is an emerging problem that restricts cancer treatment effectiveness. The proteasome inhibitor carfilzomib (CFZ) is primarily used to treat multiple myeloma and has been associated with severe renal injury in humans. CFZ-induced nephrotoxicity remains an unmet medical need, and there is an urgent need to find and develop a nephroprotective and antioxidant therapy for this condition. Thymoquinone (TQ) is a bioactive compound that has been isolated from Nigella sativa seeds. It has a wide range of pharmacological properties. Therefore, this experimental design aimed to study the effectiveness of TQ against CFZ-induced renal toxicity in rats. The first group of rats was a normal control (CNT); the second group received CFZ (4 mg/kg b.w.); the third and fourth groups received TQ (10 and 20 mg/kg b.w.) 2 h before receiving CFZ; the fifth group received only TQ (20 mg/kg b.w.). This experiment was conducted for 16 days, and at the end of the experiment, blood samples and kidney tissue were collected for biochemical assays. The results indicated that administration of CFZ significantly enhanced serum marker levels such as BUN, creatinine, and uric acid in the CFZ group. Similarly, it was also noticed that CFZ administration induced oxidative stress by reducing antioxidants (GSH) and antioxidant enzymes (CAT and SOD) and increasing lipid peroxidation. CFZ treatment also enhanced the expression of IL-1ß, IL-6, and TNF-α production. Moreover, CFZ increased caspase-3 concentrations and reduced Nrf2 expression in the CFZ-administered group. However, treatment with 10 and 20 mg/kg TQ significantly decreased serum markers and increased antioxidant enzymes. TQ treatment considerably reduced IL-1ß, IL-6, TNF-α, and caspase-3 concentrations. Overall, this biochemical estimation was also supported by histopathological outcomes. This study revealed that TQ administration significantly mitigated the negative effects of CFZ treatment on Nrf2 expression. Thus, it indicates that TQ may have utility as a potential drug to prevent CFZ-induced nephrotoxicity in the future.

Successful Treatment Using Apixaban in a Patient on Hemodialysis with Uremic Calciphylaxis.

Calciphylaxis is a rare but serious condition in which microvessel occlusion occurs within the subcutaneous adipose tissue and dermis, leading to painful lesions. End-stage renal disease requiring hemodialysis and warfarin therapy can increase the risk of calciphylaxis. In this report, we describe the evaluation and treatment of a 75-year-old female patient with warfarin-induced calciphylaxis who presented unique symptoms. The patient required intensive care unit admission due to hemodynamic instability, which was treated with inotropes and broad-spectrum intravenous antibiotics. This description of the patient's unusual symptoms has the potential to provide insights needed to improve the diagnosis of future patients. Due to the unavailability of FDA-approved treatment for calciphylaxis, its management is based on data from observational studies and clinical experience.

Design, Synthesis, Molecular Modeling and Anti-Hyperglycemic Evaluation of Quinazoline-Sulfonylurea Hybrids as Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) and Sulfonylurea Receptor (SUR) Agonists.

New quinazoline-sulfonylurea hybrids were prepared and examined for their in vivo anti-hyperglycemic activities in STZ-induced hyperglycemic rats using glibenclamide as a reference drug. Compounds VI-6-a, V, IV-4, VI-4-c, IV-6, VI-2-a, IV-1, and IV-2 were more potent than the reference glibenclamide. They induced significant reduction in the blood glucose levels of diabetic rats: 78.2, 73.9, 71.4, 67.3, 62, 60.7, 58.4, and 55.9%, respectively, while the reference glibenclamide had 55.4%. Compounds IV-1, VI-2-a, IV-2, V, and IV-6 showed more prolonged antidiabetic activity than glibenclamide. Moreover, molecular docking and pharmacokinetic studies were performed to examine binding modes of the prepared compounds against peroxisome proliferator-activated receptor gamma (PPARγ). The highest active compounds exhibited good binding affinity with high free energy of binding against PPARγ. In silico absorption, distribution, metabolism, elimination and toxicity (ADMET) studies were performed to investigate pharmacokinetics and safety of the synthesized compounds. They showed considerable human intestinal absorption with low toxicity profile.

A National Survey of Community Pharmacists' Viewpoints About Pharmacovigilance and Adverse Drug Reaction Reporting in Saudi Arabia.

This study assessed the knowledge, attitudes, and practices of community pharmacists regarding pharmacovigilance and adverse drug reaction (ADR) reporting system in Saudi Arabia. A cross-sectional survey of community pharmacists from different regions in Saudi Arabia was performed through convenience sampling between November 2020 and January 2021. The responses were received from 1,172 community pharmacists. Most respondents (86.7%) were familiar with the National Pharmacovigilance and Drug Safety Center, and 830 (70.8%) knew about the ADR reporting form. The majority (94%) of the respondents agreed with the importance of reporting ADRs for patient care and national health. Although 92.2% of the participants asked their patients about ADRs, 90.2% agreed that more training programs are required to be organized by the Saudi Food and Drug Authority for healthcare professionals on the ADR detection and reporting system. Analgesic agents were the most common drug category for which ADRs were reported (67.4%). The majority (92.1%) of ADRs reportedly occurred in patients with chronic diseases. The study concluded that most community pharmacists in Saudi Arabia are knowledgeable and have good attitudes and practices regarding pharmacovigilance and ADR reporting.

Medical students' attitudes toward sleeping pill usage: A cross-sectional study.

Medical students experience significant stress, which may interfere with their sleeping routines; consequently, they are at a higher risk of misusing sleeping pills. Therefore, this cross-sectional convenience sampling study aims to evaluate medical students' attitudes toward the usage of sleeping pills, as well as the prevalence of their misuse and the associated factors. A self-administered online questionnaire survey was completed by 338 medical students at the College of Medicine of the King Saud bin Abdulaziz University for Health Sciences. Of 338 participants, 84 (24.85%) reported using sleeping pills. The prevalence of sleeping pill misuse was 26.63% (n = 90). The most common misuse behavior of sleeping pills was self-prescription (n = 72, 21.30%). The factors associated with sleeping pill misuse were stimulants usage (n = 69, 92%, p = 0.0072), high grade point average (n = 63, 84%, p = 0.046), preclinical years (n = 52, 69.3%, p = 0.042), and longer average time required to fall asleep (n = 53, 70.7%, p = 0.008). The prevalence of sleeping pill misuse is high among medical students, particularly among those in preclinical years. Therefore, enhancing awareness regarding sleeping pill misuse is crucial. This can be achieved through campaigns, workshops, and providing information regarding the dangers of sleeping pill misuse in the curriculum.

A Review of Margetuximab-Based Therapies in Patients with HER2-Positive Metastatic Breast Cancer.

Breast cancer (BC) is the most commonly diagnosed cancer globally, with high mortality rates. Targeted drug therapies have revolutionized cancer treatment. For example, treatment with human epidermal receptor 2 (HER2) antagonists has markedly improved the prognosis of patients with HER2-positive BC (HER2 + BC). However, HER2+ metastatic BC (MBC) remains prevalent owing to its resistance to conventional anti-HER2 drugs. Therefore, novel agents are needed to overcome the limitations of existing cancer treatments and to enhance the progression-free and overall survival rates. Progress has been made by optimizing the fragment crystallizable (Fc) domain of trastuzumab, an IgG1 monoclonal, chimeric anti-HER2 antibody, to develop margetuximab. The modified Fc domain of margetuximab enhances its binding affinity to CD16A and decreases its binding affinity to CD32B, thereby promoting its antitumor activity. This review summarizes studies on the efficacy of margetuximab, discusses its utility as an anti-HER2 monoclonal antibody drug for the treatment of HER2 + BC, and presents the latest advances in the treatment of BC. This review provides insights into the clinical implication of margetuximab in HER2 + MBC treatment.

Community Pharmacy Staff Knowledge, Opinion and Practice toward Drug Shortages in Saudi Arabia.

Drug shortages continue to pose a significant threat to public health and safety. Drug shortages not only worsen patient outcomes, but also significantly burden healthcare systems with additional costs. This study aimed to assess community pharmacy staff knowledge, opinion, and practice toward drug shortages in Saudi Arabia from November 2019 to March 2020. This was a cross-sectional study carried out among 1,008 community pharmacists from Saudi Arabia using a validated, self-administered and Internet-based survey. Analysis was done using chi square and fisher exact tests. Most participants were males (97.2%), less than 30 years old (48.1%), and non-Saudi citizens (94.4%), and 72.0% had good knowledge of drug shortages (score = 4-5). Around 36.0% reported that it takes 1-3 days to receive a response to the shortage report. There was a statistically significant association between the professional level of the community pharmacists and their opinion about reporting drug shortages (P < .05). Most community pharmacies (56.2%) did not receive any notification about drug shortages. In conclusion, most community pharmacists are knowledgeable and have good practice regarding drug shortages, but their opinions about drug shortages differ according to each pharmacy reporting policy.

Substance Use and Misuse among Adults with Chronic Obstructive Pulmonary Disease in the United States, 2015-2019: Prevalence, Association, and Moderation.

BACKGROUND: Despite the advancements in chronic obstructive pulmonary disease (COPD) treatment, complications related to COPD exacerbation remain challenging. One associated factor is substance use/misuse among adults with COPD. Fewer studies, however, examined the prevalence and association between COPD and substance use and misuse. In addition, limited knowledge existed about the moderation effects of serious psychological distress and gender among adults with COPD and substance use/misuse. We aimed, therefore, to measure such prevalence, association, and moderation from nationally representative samples in the United States. METHOD: Data were drawn from the 2015-2019 National Survey on Drug Use and Health. Weighted logistic regressions were used to measure the associations of last-month tobacco (cigarettes, cigars, pipe, and smokeless tobacco products), other licit and illicit substance use (alcohol, marijuana, cocaine, crack, heroin, hallucinogens, and inhalants), and substance misuse (pain relievers, tranquilizers, stimulants, and sedatives) among adults with COPD. Serious psychological distress and gender were tested as moderators in the association between COPD and substance use/misuse. RESULTS: The findings revealed that adults with COPD [Weighted N = 53,115,718) revealed greater odds of cigarettes [adjusted odds ratio (aOR) = 2.48 (95%CI = 1.80-3.42)) and smokeless tobacco (aOR = 3.65 (95%CI = 1.75-7.65)). However, they were less likely to use alcohol (aOR = 0.61 (95%CI = 0.45-0.84)). Adults with COPD who had serious psychological distress were more likely to use pipe tobacco and alcohol; however, they were less likely to use hallucinogens and inhalants. Finally, males compared to females with COPD were less likely to use smokeless tobacco. CONCLUSION: Adults with COPD in the United States were more likely to use tobacco products and less likely to use alcohol. In addition, serious psychological distress and gender were moderators in associations between COPD and substance use but not in substance misuse. Future studies should longitudinally assess the factors that may contribute to the initiation and progression of substance use and misuse among adults with COPD.

Effects of Annona muricata Extract on Triple-Negative Breast Cancer Cells Mediated Through EGFR Signaling.

PURPOSE: To evaluate the antiproliferative activity and the mechanisms of action of Annona muricata ethyl acetate (AMEA) extract and one of its active fractions on BT-20 TNBC cells. METHODS: The triple-negative human breast cancer BT-20 cells were used. After the preparation and extraction of Annona muricata ethyl acetate (AMEA), the ethyl acetate extract was exposed to a preparative thin layer chromatography (TLC) plate. From this preparative TLC plate, eight individual bands were collected. Each band was scraped and removed from the plate and soaked in ethyl acetate. After filtration, all eight fractions were then tested on the BT-20 TNBC cells using the MTS cell viability assay. The expressions of EGFR, p-EGFR, AKT, p-AKT, MAPK, p-MAPK, cyclin D1, and NF-κB p65 were measured using Western blot analysis. RESULTS: The AMEA showed a significant decrease in NF-κB p65 protein expression and BT-20 cell viability, as determined via the MTS assay. Furthermore, the AMEA was subjected to preparative thin layer chromatography (TLC), and eight fractions were obtained. From the eight fractions, only fraction 4 (F4) showed a significant reduction in cell viability in the MTS assay. Immunoblotting analysis revealed that AMEA and F4 formed an antiproliferative effect. These effects were complemented by a downregulation of cyclin D1 assembly, causing cell-cycle arrest at the G1/S phase. Furthermore, NF-κB was measured because of its involvement in the progression of cancers. CONCLUSION: The antiproliferative influence is produced through EGFR-mediated signaling pathways, which include AKT, MAPK, NF-κB, and cyclin D1 inhibition. Further studies will be required to demonstrate the possible applications of this natural product in breast cancer therapy.

Long-Term Opioid Prescriptions After Spine Surgery: A Meta-Analysis of Prevalence and Risk Factors.

BACKGROUND: Opioids are frequently prescribed for back pain, but the prevalence of and risk factors for long-term opioid use after spine surgery were not clearly reported. We conducted a systematic review and meta-analysis to summarize the evidence for long-term opioid use (>90 days) among adults who underwent spine surgery. METHODS: PubMed, EMBASE, and Cochrane indexing databases were searched until November 9, 2018 for studies reporting the prevalence of and risk factors for long-term opioid use after spine surgery. Separate meta-analyses were conducted for commercial claims databases or registries (claims/registries) and nonclaims observational studies using the random-effects model to estimate the pooled odds ratio (OR). Prevalence meta-analysis was performed in a clinically homogeneous subset of these patients who underwent lumbar spine surgery. RESULTS: Eight claims and 5 nonclaims were meta-analyzed to avoid double-counting participants. The meta-analysis showed that preoperative opioid users (OR, 5.59; 95% confidence interval [CI], 3.37-9.27 vs. OR 4.21; 95% CI, 2.72-6.51) and participants with preexisting depression and/or anxiety (OR, 1.86, 95% CI, 1.43-2.42 and OR, 1.20; 95% CI, 0.83-1.74, respectively) had a statistically significantly higher odds of long-term postoperative opioids, compared with their peers. Males showed lower odds of long-term postoperative opioid use in the claims group (OR, 0.85; 95% CI, 0.79-0.92), but not in the nonclaims group (OR, 0.99; 95% CI, 0.71-1.39). The pooled prevalence of post-lumbar spine surgery long-term opioid use was 63% (95% CI, 50%-74%) in claims and 47% (95% CI, 38%-56%) in nonclaims. CONCLUSIONS: Patients undergoing spine surgery represent a high-risk surgical population requiring special attention and targeted interventions, with the strongest evidence for those treated with opioids before surgery and those with psychiatric comorbidities.