The use of dietary supplements for mental health among the Saudi population: A cross-sectional survey

IntroductionDespite limited evidence about the efficacy and safety of dietary supplements (DSs) for improving mental health, people with or without mental disorders often tend to use them, especially during the ongoing COVID-19 pandemic. Previous studies focused on DS use for maintaining or improving overall health; Therefore, this study aimed to assess the prevalence of DSs for mental health among the SA population and to determine the factors that affect their use.MethodsThis cross-sectional study was based on an online survey of Saudi Arabian participants between July and August 2021 with an anonymous, self-completed questionnaire distributed using convenience sampling. The questionnaire included queries related to demographic information, DS use assessment, and mental health evaluation using the Patient Health Questionnaire (PHQ-9), the Generalized Anxiety Disorder 7-item (GAD-7), questionnaire, and the Insomnia Severity Index (ISI).ResultsIn total, 443 participants from various regions of Saudi Arabia completed the questionnaire. The prevalence of DS use in the Saudi population was 44%. Vitamin D (28%) and melatonin (20%) were the most commonly reported DSs used for mental health. The odds of DS use were three times higher in responders with previous mental health diagnoses (OR: 2.972; 95% CI: 1.602–5.515). Furthermore, the chances of using DSs almost doubled in patients with sub-threshold and moderate to severe insomnia (OR: 1.930; 95% CI: 1.191–3.126 and OR: 2.485; 95% CI: 1.247–4.954, respectively).ConclusionResponders diagnosed by a specialist with psychiatric disorders or current insomnia had a higher chance of using DSs. Thus, healthcare providers must provide evidence-based information regarding DSs for mental health improvement and encourage the public to consult healthcare professionals before self-medicating for mental health problems.     

Safety and tolerability of Empagliflozin use during the holy month of Ramadan by fasting patients with type 2 diabetes: A prospective cohort study

BackgroundType 2 Diabetes Mellitus (T2DM) patients are exposed to a 7.5 times higher risk of hypoglycemia while fasting during Ramadan. Relevant diabetes guidelines prioritize the use of SGLT2 inhibitors over other classes. There is a great need to enrich data on their safe and effective use by fasting patients at greater risk of hypoglycemia. Therefore, this study aims to assess the safety and tolerability of Empagliflozin in T2DM Muslim patients during Ramadan.MethodologyA prospective cohort study was conducted for adult Muslim T2DM patients. Patients who met the inclusion criteria were categorized into two sub-cohorts based on Empagliflozin use during Ramadan (Control versus Empagliflozin). The primary outcomes were the incidence of hypoglycemia symptoms and confirmed hypoglycemia. Other outcomes were secondary. All patients were followed up to eight weeks post-Ramadan. A propensity score (PS) matching and Risk Ratio (RR) were used to report the outcomes.ResultsAmong 1104 patients with T2DM who were screened, 220 patients were included, and Empagliflozin was given to 89 patients as an add-on to OHDs. After matching with PS (1:1 ratio), the two groups were comparable. The use of other OHDs, such as sulfonylurea, DPP4 inhibitors, and Biguanides, was not statistically different between the two groups. The risk of hypoglycemia symptoms during Ramadan was lower in patients who received Empagliflozin than in the control group (RR 0.48 CI 0.26, 0.89; p-value = 0.02). Additionally, the risk of confirmed hypoglycemia was not statistically significant between the two groups (RR 1.09 CI 0.37, 3.22; p-value = 0.89).ConclusionEmpagliflozin use during Ramadan fasting was associated with a lower risk of hypoglycemia symptoms and higher tolerability. Further randomized control trials are required to confirm these findings.     

Nonsteroidal Anti-inflammatory Drugs Utilization Patterns and Risk of Adverse Events due to Drug-Drug Interactions among Elderly Patients: A Study from Jordan

BackgroundWorldwide, the prescribing pattern of the Nonsteroidal Anti-inflammatory Drugs (NSAIDs) has increased. They are considered highly effective medications in controlling various conditions including inflammatory diseases. They are associated with various adverse effects including gastrointestinal bleeding and ulcer and renal toxicity though. These adverse effects are generally potentiated when NSAIDs are co-prescribed with other drugs that share similar adverse effects and toxicities. Developing severe side effects from NSAIDs is more prone among elderly patients. Hence, it is crucial to evaluate prescribing pattern of these agents to prevent/decrease the number of unwanted side effects caused by NSAIDs.AimThe aim of this study is to assess the prescribing pattern of NSAIDs among elderly and the co-prescribing of NSAIDs and different interacting drugs, which could lead to more incidences of NSAIDs-induced toxicities among Jordanian elderly patients.Settings and MethodologyA multicenter retrospective study was performed during a three months period in Jordan. The study involves a total number of (n = 5916) elderly patient’s records obtained from Four governmental hospitals in Jordan.ResultsA total number of (n = 20450) drugs were prescribed and dispensed for patient. NSAIDs drugs prescribing percentage was 10.3% of total medications number. Aspirin was the most commonly prescribed NSAIDs among patients (70.4%), followed by Diclofenac sodium in all dosage forms (25.1%) and oral Ibuprofen (3.1%. In addition, Aspirin was the highest NSAIDs co-prescribed with ACEI (e.g., Enalapril), ARBs (e.g. Candesartan and Losartan), Diuretics (Furosemide, Indapamide, Hydrochlorothiazide, Amiloride, and Spironolactone), Warfarin and antiplatelets (Clopidogreal and Ticagrelor) followed by Diclofenac and other NSAIDs.ConclusionNSAIDs prescribing rate among elderly patients was high. Additionally the co-prescribing of NSAIDs especially Aspirin with other agents, which contributes to NSAIDs nephrotoxicity and gastrointestinal toxicity, were high. Strict measurements and action plans should be taken by prescribers to optimize the medical treatment in elderly through maximizing the benefits and decreasing the unwanted side effects.     

Pharmacy practice in hospital settings in GCC countries: Dispensing and administration

PurposeTo outline dispensing and administration practices in hospital pharmacy across the Gulf Cooperation Councils (GCC) countries’ hospitals. Paucity of data in appraising hospital pharmacy practice in GCC regions motivated us to conduct this study.MethodsA modified survey questionnaire was prepared from the American Society of Health-System Pharmacist (ASHP) survey questions. Three major domains of questions for general characteristics of the medication use process for dispensing and administration were identified. These were, (1) medication distribution system, and medication distribution technology, (2) technology used to compound sterile preparations, compounding I.V. medication and method of compounding nutrition support preparations, (3) medication administration practices, medication orders, medication administration records (MARs), and technician activities. A list of hospitals was obtained from the Ministry of Health of the targeted GCC countries. A secure invitation link containing a survey questionnaire was sent to the participants directly.ResultsSixty-four hospitals responded to this survey. The overall response rate was 52%. Most surveyed hospitals have centralized inpatient medications distribution system (75.0%). About 37.5% of hospitals used automated dispensing cabinets (ADCs) in their patient care areas. Compounding sterile preparations in the pharmacy, barcode verification technology, workflow management technology, and robotic technology were used by 17.2%, 15.6%, and 4.7% of hospitals, respectively. In using safety technology for medication administration, almost all hospitals have partially or completely implemented an electronic health record (EHR). About 40.6% of hospitals used electronic medication administration records (e-MARs), 20.3% used bar-code-assisted medication administration (BCMA), and 35.9% used smart infusion pumps.ConclusionThe results of this survey revealed an opportunity to improve the medication use management process on dispensing and administration practices in hospitals in GCC countries.     

Pharmacy practice in hospital settings in GCC countries: Prescribing and transcribing

PurposeTo outline hospital pharmacy practices across the Gulf Cooperation Councils (GCC) countries’ hospitals.MethodsA modified survey questionnaire was prepared from the original 2019 American Society of Health-System Pharmacist (ASHP) survey questions. Survey details were discussed with some pharmacy directors for clarity and relevance. A list of hospitals were obtained from the Ministry of Health of each of the targeted GCC countries. A secure invitation link containing a survey questionnaire was sent to the participants directly.ResultsSixty four hospitals responded to this survey. The overall response rate was 52%. About 47% of the surveyed hospitals considered their drug formularies as closed, and strict. Additionally, only 44% of hospitals compare the effectiveness of products, when taking formulary decisions for drug inclusion. Forty-four percent of hospitals have computerized prescriber order entry (CPOE / EHR) system functionality for formulary system management. At about 39.1% hospitals, pharmacists have the responsibility for managing medication therapies, majority were engaged in providing anticoagulation therapies. About 61% of hospital pharmacies in GCC countries receive medication orders electronically, through CPOE/EHR. Majority (66%) of the hospitals in GCC countries have an active Antimicrobial Stewardship Program (ASP) while only 40% of pharmacists have a key role in providing clinical support. About 57.8% of hospital pharmacy directors reported that pharmacists do not provide ambulatory care clinical pharmacy services in their hospitals.ConclusionIn GCC countries’ hospitals, there are major areas for improvement to patient care of which pharmacists are uniquely qualified as the medication experts to have the most meaningful outcomes in all of the domains of safe medication use, medication therapy management, antimicrobial stewardship program and participation in outpatient clinics.     

Effect of pharmacist intervention on antibiotic prophylaxis in orthopedic internal fixation: A retrospective study

BackgroundDespite the availability of guidelines and official policies, antibiotic prophylaxis in clean surgery remains suboptimal.ObjectiveThe aim of this study was to evaluate the clinical effects and cost-effectiveness of pharmacist-led intervention in the perioperative anti-infection prophylaxis of patients undergoing orthopedic internal fixation.MethodsWe performed a retrospective analysis based on the medical records of internal fixation surgery in a tertiary hospital from July 2019 to June 2020. Data were divided into two groups based on whether a full-time pharmacist participated in the treatment. The research parameters included use of antibiotics, rationality of medication, postoperative complications, and related cost. To deal with selection bias, propensity score matching method was employed at a ratio of 1:1. Meanwhile, a cost-effectiveness analysis was used to evaluate the impact of pharmacist intervention on antibiotic prevention in internal fixation surgery.ResultsA total of 537 participants were included in this study. After matching, 236 patients were comparable in each group. During the pharmacist intervention period, less pharmacologic prophylaxis (96.6% vs 100.0%, p = 0.007) and shorter prophylaxis duration (1.60 vs 2.28 days, p < 0.001) were observed. The reasonable rate increased dramatically in usage and dosage (96.6% vs 83.9%, p < 0.001), timing of administration (94.5% vs 78.4%, p < 0.001) and medication duration (64.4% vs 37.7%, p < 0.001). In addition, pharmacist intervention yielded net economic benefits. A remarkable reduction was observed in average length of stay (10.43 vs 11.14 days, p = 0.012), drug cost ($610.57 vs $706.60, p = 0.001) and defined daily doses (2.31 vs 3.27, p < 0.001). The cost-effectiveness ratios, divided drug cost savings by cost of pharmacist time, were 28:1 for drug and 2:1 for antibiotics, respectively.ConclusionPharmacist-driven antibiotic stewardship for orthopedic internal fixation patients improved compliance with peri-procedure antibiotic prophylaxis, and reduced the cost and utilization of antibiotics. This helped to bring significant clinical and economic benefits.     

Crosstalk among colon cancer-derived exosomes,fibroblast-derived exosomes,and macrophage phenotypes in colon cancer metastasis

Cellular crosstalk is an important mechanism in the pathogenesis of inflammatory disorders and cancers. One significant means by which cells communicate with each other is through the release of exosomes. Exosomes are extracellular vesicles formed by the outward budding of plasma membranes, which are then released from cells into the extracellular space. Many studies have suggested that microvesicles released by colon cancer cells initiate crosstalk and modulate the fibroblast activities and macrophage phenotypes. Interestingly, crosstalk among colon cancer cells, macrophages and cancer-associated fibroblasts maximizes the mechanical composition of the stromal extracellular matrix (ECM). Exosomes contribute to cancer cell migration and invasion, which are critical for colon cancer progression to metastasis. The majority of the studies on colorectal cancers (CRCs) have focused on developing exosomal biomarkers for the early detection and prediction of CRC prognosis. This study highlights the crosstalk among colon cancer-derived exosomes, macrophage phenotypes and fibroblasts during colon cancer metastasis.     

Prevalence of complementary and alternative medicine use among rheumatoid arthritis patients in Saudi Arabia

Background and aimThe use of complementary and alternative medicine (CAM) is unexplored among Saudi rheumatoid arthritis (RA) patients. The aim of this study was to estimate the prevalence and types of CAM used among patients with RA and factors associated with their use.Experimental procedureA cross-sectional study was conducted at rheumatology clinics in two tertiary hospitals located in Riyadh, Saudi Arabia. The data was collected between May 2017 and February 2018. Unpaired Student's t-tests, Chi-square tests, and Pearson correlation tests were used to compare users vs nonusers.ResultsA total of 438 patients (mean age = 49, SD ± 15 years; 89.7% females) were included in this study. Sixty seven percent of included patients had used CAM for their RA. The majority of CAM users were female (92.1%). The most frequently used CAM products were vitamin D (47%), calcium (37%), honey (15%), ginger (13%), turmeric (11%), black seeds (8%), and fenugreek (8%). One hundred ninety-six (45%) patients believe that CAM is safe, and 287 (96%) patients took it because they believed that CAM had “added benefits”. Statistically significant differences were found for gender, RA duration, erythrocyte sedimentation rate (ESR) level, and seropositivity between CAM users and nonusers (P = 0.019, P = 0.011, P = 0.022, and P < 0.0001, respectively). A significant correlation was found between the Erythrocyte Sedimentation Rate (ESR) level, RA duration and CAM use (r = 0.110, P = 0.022 and r = 0.121, P = 0.012, respectively). These data indicated that patients who used CAM had higher ESR level and longer disease duration than patients didn’t use CAM.ConclusionThere is a high prevalence of CAM use among RA patients. CAM use was perceived to add benefit and patients using it had higher ESR. Larger studies are needed to assess the use of CAM and its impact on RA and its management.     

A study of the role of DIO1 and DIO2 polymorphism in thyroid cancer and drug response to therapy in the Saudi population

BackgroundDeiodinases comprise a group of selenoproteins that regulate the bioavailability of active thyroid hormones (TH) in a time and tissue specific fashion. They increase the hormonal activity by metabolizing their inactive precursors to active forms or terminate their activity by deactivating active hormones. The role of the deiodinase (DIO) gene polymorphisms in thyroid cancer is not fully understood yet. This study evaluated the potential association of the DIO1 and DIO2 genes with differentiated thyroid cancer and differential thyroxine dose requirement in thyroidectomized patients in a Saudi cohort.MethodsWe selected four variants (one DIO1 and three DIO2) for the association studies using Taqman assays in 507 DTC patients undergoing treatment with thyroxin against 560 disease-free individual, all of Saudi Arab origin.ResultsNone of the studied variants was linked to differentiated thyroid cancer. The rs1388378_G > T was initially linked to thyroxine dose requirement (p = 0.035) when all patients were considered together, but this association was lost when the patients were classified into either near suppressed (0.1 ≤ TSH < 0.5) or suppressed (TSH < 0.1) TSH group.DiscussionAlthough the results suggest only a weak relationship with differentiated thyroid cancer, they strongly indicate that the DIO2 polymorphism influences the hormonal dose requirement in patients undergoing treatment with thyroxine. This probably points to a distinction in the way this gene influences disease as compared to therapy thereof.     

Assessment of knowledge,attitude, and practices of acute kidney injury incidence with co-administration of piperacillin/tazobactam and vancomycin among healthcare workers: A cross-sectional study

BackgroundNo studies have identified a link between acute kidney injury (AKI) incidence due to the co-administration of vancomycin and piperacillin/tazobactam (VPT) and healthcare providers’ knowledge, attitudes, and practices. We aimed to (1) assess the knowledge, attitudes, and practices towards AKI due to VPT co-administration among healthcare providers in Saudi Arabia, and (2) examine the relationship between healthcare providers’ knowledge and attitudes about AKI due to VPT co-administration and their practices.MethodsThis cross-sectional study was conducted between February 2022 and April 2022. Healthcare providers, including physicians, pharmacists, and nurses, were included in the study population. The correlation coefficient assessed the relationship between knowledge, attitude, and practice. Spearman’s rho was used as a test statistic.ResultsOf the invited healthcare providers, 192 responded to the survey. A significant difference in knowledge was found among healthcare providers for two variables: the definition of AKI (p < 0.001) and appropriate management of AKI due to VPT (p = 0.002). Physicians were found to rely less on the most common causative organisms of infection to guide empirical antibiotic therapy (p < 0.001). In addition, physicians were less likely to switch piperacillin/tazobactam to cefepime or meropenem in combination with vancomycin with AKI incidence (p = 0.001). A positive attitude towards the perceived AKI risk with VPT was positively correlated with avoiding using VPT unless no alternatives were available (Rho = 0.336) and taking protective measures when using VPT (Rho = 0.461).ConclusionDeviation has been observed in the knowledge, attitudes, and practices of AKI incidence with the co-administration of piperacillin/tazobactam and vancomycin among healthcare workers. Interventions at the organizational level are recommended to guide best practices.     

Pharmacy student’s perceptions,behaviours and attitudes toward virtual reality simulation

AimsThe definition of virtual reality simulation (VRS) used for study is the recreation of realistic simulation in a fully online situation with an immersive environment for learning an activity. The study aims to evaluate pharmacy students’ perspectives, behavioral and attitude characteristics in the process of VRS course requiring practical skills.Materials and methodsThis cross-sectional study was based on quantitative questionnaires analysis. A five-point Likert Scale (rating from 1 = Strongly Disagree; 2 = Disagree; 3 = Neutral; 4 = Agree; 5 = Strongly Agree) was utilized to measure the extent to which the students agrees on 30 statements comprised in A-E sections related to VRS. The validity and reliability of the questionnaire were studied by the Cronbach’s Alpha calculation.ResultsA total of 119 junior and senior pharmacy students, aged 18–25, participated in this study. There is no significant gender difference (P > 0.05) and grade difference (P > 0.05) in mean perception score, mean attitude score, mean behavior score and comparison score respectively. Most pharmacy students had positive perception that VRS could help them in practical ability (61.4 %), autonomous learning (68.9 %) and theoretical knowledge (61.4 %). Nevertheless, less than half the students agreed that VRS courses were indispensable (44.5 %) and needed to be increased (42.9 %). Moreover, the ‘disagree’ statement (33.6 %) exceeded ‘agree’ statement (27.7 %) about the question of whether preferring VRS courses to lab teaching. Interestingly, a significant positive correlation that was observed between mean perception score and mean attitude score (r = 0.76, p < 0.001), mean comparison (r = 0.68, p < 0.001) and mean behavior (r = 067, p < 0.001), which revealed that students who thought VRS was beneficial were more likely to accept it.ConclusionThe study highlights the need to establish an interactive, immersive and measurable VRS courses. It is suggested that good interaction between the faculty and student, technology improvement and blended programmatic assessment should be involved in challenges for implementing VRS courses.     

Comparing the impact of Hydroxychloroquine based regimens and standard treatment on COVID-19 patient outcomes: A retrospective cohort study

BackgroundPharmacological treatments including antivirals (Lopinavir/Ritonavir), Immuno-modulatory and anti-inflammatory drugs including, Tocilizumab and Hydroxychloroquine (HCQ) has been widely investigated as a treatment for COVID-19.Despite the ongoing controversies, HCQ was recommended for managing mild to moderate cases in Saudi Arabia . However, to our knowledge, no previous studies have been conducted in Saudi Arabia to assess its effectiveness.MethodsA hospital-based retrospective cohort study involving 161 patients with COVID-19 was conducted from March 1 to May 20, 2020. The study was conducted at Prince Mohammed bin Abdul Aziz Hospital (PMAH).The population included hospitalized adults (age ≥ 18 years) with laboratory-confirmed COVID-19. Each eligible patient was followed from the time of admission until the time of discharge. Patients were classified into two groups according to treatment type: in the HCQ group, patients were treated with HCQ; in the SC group, patients were treated with other antiviral or antibacterial treatments according to Ministry of Health (MOH) protocols.The outcomes were hospitalization days, ICU admission, and the need for mechanical ventilation.We estimated the differences in hospital length of stay and time in the ICU between the HCQ group and the standard care (SC) group using a multivariate generalized linear regression. The differences in ICU admission and mechanical ventilation were compared via logistic regression. All models were adjusted for age and gender variables.ResultsA total of 161 patients fulfilled the inclusion criteria. Approximately 59% (n = 95) received HCQ-based treatment, and 41% (n = 66) received SC. Length of hospital stay and time in ICU in for patients who received HCQ based treatment was shorter than those who received SC. Similarly, there was less need for ICU admission and mechanical ventilation among patients who received HCQ based treatment compared with SC, (8.6% vs. 10.7 and 3.1% vs. 9.1%). However, the regression analysis showed no significant difference between the two groups in terms of patient outcomes.ConclusionHCQ had a modest effect on hospital length stay and days in ICU compared with SC. However, these results need to be interpreted with caution. Larger observational studies and RCTs that evaluate the efficacy of HCQ in COVID-19 patients in the Saudi population are urgently needed.     

CRISPR-Cas9 in Alzheimer’s disease: Therapeutic trends,modalities, and challenges

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Targeting regulated cell death (RCD) with small-molecule compounds in cancer therapy: A revisited review of apoptosis,autophagy-dependent cell death and necroptosis

Evasion of regulated cell death (RCD), mainly referring to apoptosis, autophagy-dependent cell death, necroptosis, and other subroutines, is one of the well-established hallmarks of cancer cells. Accumulating evidence has revealed several small-molecule compounds that target different subroutines of RCD in cancer therapy. In this review, we summarize key pathways of apoptosis, autophagy-dependent cell death and necroptosis in cancer, and describe small-molecule compounds that target these pathways and have potential as therapeutics. These inspiring findings light the way towards the discovery of more ‘magic bullets’ that could work individually or cooperatively to target precisely the three RCD subroutines and so improve cancer treatment.     

Chloroquine,hydroxychloroquine, and COVID-19: Systematic review and narrative synthesis of efficacy and safety

The COVID-19 pandemic has required clinicians to urgently identify new treatment options or the re-purposing of existing drugs. Of particular interest are chloroquine (CQ) and hydroxychloroquine (HCQ). The aims of this systematic review are to systematically identify and collate 24 studies describing the use of CQ and HCQ in human clinical trials and to provide a detailed synthesis of evidence of its efficacy and safety. Of clinical trials, 100% showed no significant difference in the probability of viral transmission or clearance in prophylaxis or therapy, respectively, compared to the control group. Among observational studies employing an endpoint specific to efficacy, 58% concurred with the finding of no significant difference in the attainment of outcomes. Three-fifths of clinical trials and half of observational studies examining an indicator unique to drug safety discovered a higher probability of adverse events in those treated patients suspected of, and diagnosed with, COVID-19. Of the total papers focusing on cardiac side-effects, 44% found a greater incidence of QTc prolongation and/or arrhythmias, 44% found no evidence of a significant difference, and 11% mixed results. The strongest available evidence points towards the inefficacy of CQ and HCQ in prophylaxis or in the treatment of hospitalised COVID-19 patients.     

Safety and efficacy of Rituximab in systemic sclerosis: A systematic review and meta-analysis

PurposeRituximab is widely prescribed to treat systemic sclerosis (SSc) by the depletion of pathogenic B cells. Nonetheless, the clinical benefit of Rituximab in SSc remains contentious. This meta-analysis was conducted to systematically evaluate the safety and efficacy profile of Rituximab in SSc patients.Patients and methodsWe performed a systematic online query in PubMed, Cochrane, and Web of Science. The available studies on the use of Rituximab in SSc patients were comprehensively reviewed and investigated.ResultsIn total, 14 studies, including 597 participants, were analyzed. Pooled results showed the long-term improvement in the modified Rodnan skin score (mRSS) for skin function (ΔmRSS: 7.00 at 6 months, 9.70 at 12 months, and 10.93 at 24 months), while forced vital capacity (FVC) (ΔFVC: −0.69 at 6 months, −2.62 at 12 months, and −0.67 at 24 months) and diffusing capacity of the lungs for carbon monoxide (DLCO) (ΔDLCO: −2.39 at 6 months, −3.28 at 12 months, and −0.79 at 24 months) for lung function remained stable in SSc patients after Rituximab treatment. The rate of Rituximab-related adverse events was 12% in the pooled results.ConclusionThe pooled results of this meta-analysis indicated that Rituximab is well tolerated, and it is able to improve cutaneous function and stabilize pulmonary function in SSc patients.     

Mitochondrial-targeted nanoparticles: Delivery and therapeutic agents in cancer

Antitumor agents are delivered via nanoparticles (NPs) to the mitochondria. The drugs attack the mitochondria resulting in mitochondrial damage and the release of cytochrome C (Cyto-C). Cyto-C binds with Apaf1 and Caspase-9 to form an apoptosome. The apoptosome activates Caspase 3, which ultimately results in the death of cancer cells.

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