Synthesis, cytotoxicity, anti-inflammatory, anti-metastatic and anti-oxidant activities of novel chalcones incorporating 2-phenoxy-N-arylacetamide and thiophene moieties: induction of apoptosis in MCF7 and HEP2 cells.

Eight Novel chalcones were synthesized and their structures were confirmed by different spectral tools. All the prepared compounds were subjected to SRB cytotoxic screening against several cancer cell lines. Compound 5c exerted the most promising effect against MCF7 and HEP2 cells with IC50 values of 9.5 and 12 µg/mL, respectively. Real-time PCR demonstrated the inhibitory effect of compound 5c on the expression level of Antigen kiel 67 (KI-67), Survivin, Interleukin-1beta (IL-1B), Interleukin-6 (IL-6), Cyclooxygenase-2 (COX-2) and Protein kinase B (AKT1) genes. Flow-cytometric analysis of the cell cycle indicated that compound 5c stopped the cell cycle at the G0/G1 and G2/M phases in MCF7 and HEP2 treated cells, respectively. ELISA assay showed that Caspase 8, Caspase 9, P53, BAX, and Glutathione (GSH) were extremely activated and Matrix metalloproteinase 2 (MMP2), Matrix metalloproteinase 9 (MMP9), BCL2, Malondialdehyde (MDA), and IL-6 were deactivated in 5c treated MCF7 and HEP2 cells. Wound healing revealed that chalcone 5c reduced the ability to close the scrape wound and decreased the number of migrating MCF7 and HEP2 cells compared to the untreated cells after 48 h. Theoretical molecular modeling against P53 cancer mutant Y220C and Bcl2 showed binding energies of -22.8 and -24.2 Kcal/mole, respectively, which confirmed our ELISA results.

Corneal confocal microscopy detects early nerve regeneration after pharmacological and surgical interventions: Systematic review and meta-analysis.

Corneal confocal microscopy (CCM) is an ophthalmic imaging technique that enables the identification of corneal nerve fibre degeneration and regeneration. To undertake a systematic review and meta-analysis of studies utilizing CCM to assess for corneal nerve regeneration after pharmacological and surgical interventions in patients with peripheral neuropathy. Databases (EMBASE [Ovid], PubMed, CENTRAL and Web of Science) were searched to summarize the evidence from randomized and non-randomized studies using CCM to detect corneal nerve regeneration after pharmacological and surgical interventions. Data synthesis was undertaken using RevMan web. Eighteen studies including 958 patients were included. CCM identified an early (1-8 months) and longer term (1-5 years) increase in corneal nerve measures in patients with peripheral neuropathy after pharmacological and surgical interventions. This meta-analysis confirms the utility of CCM to identify nerve regeneration following pharmacological and surgical interventions. It could be utilized to show a benefit in clinical trials of disease modifying therapies for peripheral neuropathy.

Osteonecrosis of the Femoral Head as a Potential Pitfall in 18 F-PSMA-1007 PET.

ABSTRACT: PSMA-targeted PET agents are mainly involved for prostate cancer; however, unspecific bone uptakes can be challenging for the clinician. We report the case of a 71-year-old man with history of recurrent prostate cancer initially treated by surgery and radiation therapy. 18 F-PSMA 1007 PET/CT was performed. Beside hyperfixing lymph nodes, focal uptake was found in right femoral head with shell subchondral hypofixation and no morphologic correlate on CT. MRI found bilateral osteonecrosis of the femoral head. This case emphasizes that osteonecrosis of the femoral head can mimic a metastasis uptake, even with normal CT, without however the fixation being constant.

Novel 3-(pyrazol-4-yl)-2-(1H-indole-3-carbonyl)acrylonitrile derivatives induce intrinsic and extrinsic apoptotic death mediated P53 in HCT116 colon carcinoma.

A novel series of α-cyano indolylchalcones was prepared, and their chemical structures were confirmed based on the different spectral data. Among them, compound 7f was observed to be the most effective bioactive chalcone with distinguished potency and selectivity against colorectal carcinoma (HCT116) with IC50 value (6.76 µg/mL) relative to the positive control (5 FU) (77.15 µg/mL). In a preliminary action study, the acrylonitrile chalcone 7f was found to enhance apoptotic action via different mechanisms like inhibition of some anti-apoptotic protein expression, regulation of some apoptotic proteins, production of caspases, and cell cycle arrest. All mechanisms suggested that compound 7f could act as a professional chemotherapeutic agent. Also, a molecular docking study was achieved on some selected proteins implicated in cancer (Caspase 9, XIAP, P53 mutant Y220C, and MDM2) which showed variable interactions with compound 7f with good Gibbs free energy scores.

Novel Scaffolds Based on Bis-thiazole Connected to Quinoxaline or Thienothiophene through 2-Phenoxy-N-arylacetamide Groups as New Hybrid Molecules: Synthesis, Antibacterial Activity, and Molecular Docking Investigations.

The resistance of microorganisms to antimicrobials has endangered the health of many people across the world. Overcoming the resistance problem will require the invention of molecules with a new mechanism of action so that no cross-resistance with existing therapies occurs. Because of their powerful antibacterial activity against a wide spectrum of Gram-positive and Gram-negative bacterial strains, heterocyclic compounds are appealing candidates for medicinal chemists. In this regard, as unique hybrid compounds, we synthesized a novel family of bis-thiazoles linked to quinoxaline or thienothiophene via the 2-phenoxy-N-arylacetamide moiety. The target compounds were synthesized by reacting the relevant bis(α-haloketones) with the corresponding thiosemicarbazones in EtOH at reflux with a few drops of TEA. Under comparable reaction conditions, the isomeric bis(thiazoles) were synthesized by reacting the appropriate bis(thiosemicarbazone) with the respective α-haloketones. The structures of the novel compounds were confirmed using elements and spectral data. All of the synthesized compounds were tested for antibacterial activity in vitro. With an inhibitory zone width of 12 mm, compound 12a had the same activity as the reference medication tobramycin against Staphylococcus aureus. Compound 12b showed 20 mg/mL as a minimum inhibitory concentration (MIC) against Bacillus subtilis. Some of the synthesized compounds were tested via molecular docking against two bacterial proteins (dihydrofolate reductase and tyrosyl-tRNA synthetase).

Impact of trifluoromethyl and sulfonyl groups on the biological activity of novel aryl-urea derivatives: synthesis, in-vitro, in-silico and SAR studies.

We designed and prepared a novel series of urea derivatives with/without sulfonyl group in their structures to investigate the impact of the sulfonyl group on the biological activity of the evaluated compounds. Antibacterial investigations indicated that derivatives 7, 8, 9, and 11 had the most antibacterial property of all the compounds examined, their minimum inhibitory concentrations (MICs) determined against B. mycoides, E. coli, and C. albicans, with compound 8 being the most active at a MIC value of 4.88 µg/mL. Anti-cancer activity has been tested against eight human cancer cell lines; A549, HCT116, PC3, A431, HePG2, HOS, PACA2 and BJ1. Compounds 7, 8 and 9 emerged IC50 values better than Doxorubicin as a reference drug. Compounds 7 and 8 showed IC50 = 44.4 and 22.4 µM respectively against PACA2 compared to Doxorubicin (IC50 = 52.1 µM). Compound 9 showed IC50 = 17.8, 12.4, and 17.6 µM against HCT116, HePG2, and HOS, respectively. qRT-PCR revealed the down-regulation of PALB2 in compounds 7 and 15 treated PACA2 cells. Also, the down-regulation of BRCA1 and BRCA2 was shown in compound 7 treated PC3 cells. As regard A549 cells, compound 8 decreased the expression level of EGFR and KRAS genes. While compounds 7 and 9 down-regulated TP53 and FASN in HCT116 cells. Molecular docking was done against Escherichia coli enoyl reductase and human Son of sevenless homolog 1 (SOS1) and the results showed the promising inhibition of the studied proteins.

Design, synthesis, in vitro anticancer, molecular docking and SAR studies of new series of pyrrolo[2,3-d]pyrimidine derivatives.

The current study involves the design and synthesis of a newly synthesized pyrrolo[2,3-d]pyrimidine derivatives to contain chlorine atoms in positions 4 and 6 and trichloromethyl group in position 2 using microwave technique as a new and robust approach for preparation of this type of pyrrolo[2,3-d]pyrimidine derivatives. The chemical structure of the synthesized pyrrolo[2,3-d]pyrimidine derivatives 3-19 was well-characterized using spectral and elemental analyses as well as single-crystal X-ray diffraction. All compounds were tested in vitro against seven selected human cancer cell lines, namely, MCF7, A549, HCT116, PC3, HePG2, PACA2 and BJ1 using MTT assay. It was found that compounds 14a, 16b and 18b were the most active toward MCF7 with IC50 (1.7, 5.7, and 3.4 µg/ml, respectively) relative to doxorubicin (Dox.) (26.1 µg/ml). Additionally, compound 17 exerted promising cytotoxic effects against HePG2 and PACA2 with IC50 (8.7 and 6.4 µg/ml, respectively) relative to Dox. (21.6 and 28.3 µg/ml, respectively). The molecular docking study confirmed our ELISA result which showed the promising binding affinities of compounds 14a and 17 against Bcl2 anti-apoptotic protein. At the gene expression level, P53, BAX, DR4 and DR5 were up-regulated, while Bcl2, Il-8, and CDK4 were down-regulated in 14a, 14b and 18b treated MCF7 cells. At the protein level, compound 14b increased the activity of Caspase 8 and BAX (18.263 and 14.25 pg/ml) relative to Dox. (3.99 and 4.92 pg/ml, respectively), while the activity of Bcl2 was greatly decreased in 14a treated MCF7 (2.4 pg/ml) compared with Dox. (14.37 pg/ml). Compounds 14a and 14b caused cell cycle arrest at the G1/S phase in MCF7. Compounds 16b and 18b induced the apoptotic death of MCF7 cells. In addition, the percentage of fragmented DNA was increased significantly in 14a treated MCF7 cells.

Prevalence, types and disclosure of complementary and alternative medicine (CAM) use among chronic kidney disease (CKD) patients in Saudi Arabia.

INTRODUCTION: Despite the paucity of scientific evidence, CAM is widely used for the prevention and treatment of illness among patients with chronic kidney disease, including end-stage renal disease and kidney transplant recipients. It is evident that the irrational use of CAM among CKD patients and its non-disclosure to healthcare providers could lead to adverse drug events. Hence, the current study was conducted to evaluate the prevalence, types, and non-disclosure of CAM use among CKD patients and kidney transplant recipients in Saudi Arabia. METHODS: A cross-sectional study was conducted on 170 CKD patients (121 with stages 3 and 4, two with stage 5 and on hemodialysis, and 47 kidney transplant recipients). Face-to-face questionnaire-based interviews were conducted employing a convenience sampling technique. The study outcomes were the prevalence of CAM, types of CAM use, monthly expenditure on CAM, the source of information about CAM, and CAM disclosure to healthcare providers. A p-value of < 0.05 was considered significant. RESULTS: The study found that out of 170, 60 (35.3%) CKD patients use CAM. The most used CAM was Acacia gum (49, 81.6%) followed by spiritual therapies (34, 56.6%). Female CKD patients had higher use of CAM compared to the male gender (p = 0.015). The monthly expenditures that most users (47, 78.3%) spent on CAM were less than 50 Saudi Riyals (SR). The study results also showed that 55% of CKD patients did not report their CAM use to their physicians. Furthermore, 46.6% of CAM users discontinue their use of CAM after observing no benefit. CONCLUSION: This study reported relatively high use of CAM among CKD patients in Saudi Arabia. The study found that most CKD patients use Acacia gum and spiritual therapies and do not disclose the use of CAM to healthcare professionals, which could lead to adverse drug events. Therefore, the study recommends that healthcare providers should inquire and provide evidence-based counselling about the use of CAM to CKD patients to prevent any adverse drug event or unwanted effect on the renal function of the patients.

A Cross-Sectional Study to Investigate the Prevalence of Self-Medication of Non-Opioid Analgesics Among Medical Students at Qassim University, Saudi Arabia.

Purpose: Self-medication (SM) using non-opioid analgesics (NOA) is contentious and increasingly recognized as a major public health concern with severe consequences, including masking of malignant and fatal diseases, risk of misdiagnosis, problems relating to over- and under-dosing, drug interactions, incorrect dosage, and choice of therapy. Herein, we aim to determine the prevalence of SM with NOA among pharmacy and medical students at Unaizah College, Qassim University, Saudi Arabia. Patients and Methods: A cross-sectional study using a validated self-administered questionnaire was conducted on 709 pharmacy and medicine students belonging to an age group of 21-24 years from Unaizah Colleges. Data were statistically analyzed using SPSS version 21. Results: Of 709 participants, 635 responded to the questionnaire. Our results showed a prevalence percentage of 89.6% using self-medicated NOA for pain management. The most common factor leading to SM in NOA was the mild nature of the illness (50.6%), and headache/migraine (66.8%) was the dominant health problem. Paracetamol (acetaminophen, 73.7%) was the most commonly used analgesic, followed by ibuprofen (16.5%). The most common and reliable sources of drug information were pharmacists (51.5%). Conclusion: We observed a high rate of SM for NOA among undergraduate students. We believe that the adverse consequences of SM could be controlled through educational, regulatory, and administrative strategies by providing appropriate awareness sessions, and the role of pharmacists should be highlighted in preventing SM from NOA.

Public Awareness Regarding Household Drug Storage, Qassim Region, Saudi Arabia: A Cross-Sectional Study.

Background: Little is known regarding the post-dispensing storage conditions for pharmaceuticals in Saudi Arabia (SA). Most parts of the region are usually hot and humid, which could result in the decline of crucial performance parameters. Objective: To determine the prevalence of household drug storage habits in the population of Qassim, and to investigate their storage behaviors as well as knowledge and awareness of factors that may affect drug stability. Methods: A cross-sectional study was conducted using a simple random sampling technique in the Qassim region. Data were collected over a period of 3 months using a well-structured self-administered questionnaire and analyzed using SPSS version 23. Results: More than six hundred households from all regions of Qassim in SA participated in this study. Approximately 95% of the participants stored 1-5 drugs at home. Analgesics and antipyretics were the highest household reported drugs (71.9%), with tablets and capsules dosage forms (72.3%). More than half of the participants (54.6%) stored drugs in their home refrigerators. Approximately 45% of the participants regularly checked the expiry dates of household drugs and immediately discarded them once their color changed. Only 11% of the participants shared drugs with others. We found that the number of drugs stored at home is heavily influenced by the number of family members in general and the number of members with medical issues in particular. Moreover, Saudi female participants with higher levels of education demonstrated better behaviors in terms of ensuring appropriate conditions for household drug storage. Conclusion: The majority of participants stored drugs in the home refrigerator or other easily accessible places, which may lead to toxicity or health risks, particularly for children. Therefore, population education and awareness programs should be implemented to raise awareness about the consequences of drug storage conditions in terms of the stability, efficacy, and safety of medications.

Incidence and risk factors of bladder injury during cesarean delivery: a cohort study.

PURPOSE: To identify risk factors associated with bladder injury during cesarean delivery, and to determine the frequency of associated morbidities. METHODS: Data obtained from the United States' Health Care Cost and Utilization Project-Nationwide Inpatient Sample were used to conduct a retrospective population-wide cohort study. ICD-9 codes were used to identify women who underwent a cesarean delivery between 1999 and 2015. Subsequently, women were classified based on whether or not they experienced a bladder injury during delivery. Multivariate logistic regression was used to determine predictors of bladder injury in cesarean deliveries and to examine the associated morbidities while adjusting for baseline maternal demographics and clinical characteristics. RESULTS: Of 4,169,681 cesarean deliveries identified, there were 7,627 (0.2%) bladder injuries for an overall incidence of 18 per 10,000. Women ≥ 35 years were at greater risk of bladder injury 1.5 (1.4-1.6), as were women with endometriosis 2.0 (1.5-2.7) and Crohn's disease 2.7 (1.7-4.2). Risk of bladder injury increased if the cesarean delivery was associated with placenta previa 2.2 (1.9-2.4), previous cesarean delivery 4.3 (4.1-4.6), failed instrumental delivery 4.1 (3.5-4.8), fetal distress 1.7 (1.6-1.8), failed trial of labor after cesarean delivery 1.3 (1.2-1.4), and labor dystocia 1.7 (1.6-1.8). Cesarean hysterectomies presented the greatest risk for bladder injury 37.0 (33.7-40.6). Bladder injury was associated with an increased frequency of sepsis, venous thromboembolism, peritonitis, blood transfusions and longer hospital stays. CONCLUSION: Bladder injury during cesarean deliveries is a rare outcome but it is more common among women with certain demographic and clinical characteristics. Among these cases, strategies to prevent sepsis and venous thromboembolism should be considered.

Self-Organization of Lipid-Porphyrin Conjugates at the Air/Water Interface.

Lipid-porphyrin conjugates are versatile compounds which can self-assemble into liposome-like structures with multifunctional properties. Most of the conjugates that have been described so far, consisted in grafting pyropheophorbide-a (Pyro-a) or other porphyrin derivatives through the esterification of the hydroxyl group in the sn-2 position of a lysophosphatidylcholine. However, despite the versatility of these conjugates, less is known about the impact of the lipid backbone structure on their 2D phase behavior at the air/water interface and more precisely on their fine structures normal to the interface as well as on their in-plane organization. Herein, we synthesized a new lipid-porphyrin conjugate (PyroLSM) based on the amide coupling of Pyro-a to a lysosphingomyelin backbone (LSM) and we compared its interfacial behavior to that of Pyro-a and Pyro-a conjugated lysophosphatidylcholine (PyroLPC) using Langmuir balance combined to a variety of other physical techniques. Our results provided evidence on the significant impact of the lipid backbone on the lateral packing of the conjugates as well as on the shape and size of the formed domains. Compared to Pyro-a and PyroLPC monolayers, PyroLSM exhibited the highest lateral packing which highlights the role of the lipid backbone in controlling their 2D organization which in turn may impact the photophysical properties of their assemblies.

Theoretical and molecular mechanistic investigations of novel (3-(furan-2-yl)pyrazol-4-yl) chalcones against lung carcinoma cell line (A549).

A new chalcone series has been developed that may be useful in the treatment of lung cancer. The new series was confirmed by the different spectral tools. MTT assay was used to detect the cytotoxic effect of the novel chalcones against lung cancer cell line (A549). Molecular docking studies were performed on the most two effective chalcones 7b and 7c. Different molecular techniques were utilized to study the activity and the effect of two chalcones 7b and 7c on apoptosis of A549 cell line.

A Polymer Prodrug Strategy to Switch from Intravenous to Subcutaneous Cancer Therapy for Irritant/Vesicant Drugs.

Chemotherapy is almost exclusively administered via the intravenous (IV) route, which has serious limitations (e.g., patient discomfort, long hospital stays, need for trained staff, high cost, catheter failures, infections). Therefore, the development of effective and less costly chemotherapy that is more comfortable for the patient would revolutionize cancer therapy. While subcutaneous (SC) administration has the potential to meet these criteria, it is extremely restrictive as it cannot be applied to most anticancer drugs, such as irritant or vesicant ones, for local toxicity reasons. Herein, we report a facile, general, and scalable approach for the SC administration of anticancer drugs through the design of well-defined hydrophilic polymer prodrugs. This was applied to the anticancer drug paclitaxel (Ptx) as a worst-case scenario due to its high hydrophobicity and vesicant properties (two factors promoting necrosis at the injection site). After a preliminary screening of well-established polymers used in nanomedicine, polyacrylamide (PAAm) was chosen as a hydrophilic polymer owing to its greater physicochemical, pharmacokinetic, and tumor accumulation properties. A small library of Ptx-based polymer prodrugs was designed by adjusting the nature of the linker (ester, diglycolate, and carbonate) and then evaluated in terms of rheological/viscosity properties in aqueous solutions, drug release kinetics in PBS and in murine plasma, cytotoxicity on two different cancer cell lines, acute local and systemic toxicity, pharmacokinetics and biodistribution, and finally their anticancer efficacy. We demonstrated that Ptx-PAAm polymer prodrugs could be safely injected subcutaneously without inducing local toxicity while outperforming Taxol, the commercial formulation of Ptx, thus opening the door to the safe transposition from IV to SC chemotherapy.

Validation and Cultural Adaptation of the Parent Attitudes about Childhood Vaccines (PACV) Questionnaire in Arabic Language Widely Spoken in a Region with a High Prevalence of COVID-19 Vaccine Hesitancy.

The parents' attitude toward vaccinating children and adolescents against coronavirus disease 2019 (COVID-19) remains inconsistent and needs further elucidation. The high rates of COVID-19 vaccine hesitancy in the Middle East and North Africa (MENA) region require intensive research to understand the determinants of this phenomenon. This study aimed to validate a version of the Parent Attitudes about Childhood Vaccines (PACV) tool in Arabic, the most widely spoken language in the MENA. The study objectives included the investigation of Arab-speaking parents' views regarding COVID-19 vaccination of their children. Parents living in Egypt with at least one child aged 5−18 years were eligible to participate in the study that was conducted through an online survey with 15 PACV items. The PACV tool was translated into Arabic using forward and backward translation. To assess the psychometric properties of the Arabic version of PACV, Pearson's correlation coefficient and exploratory and confirmatory factor analysis (EFA and CFA) were performed. A total of 223 parents participated in the study: 59.82% aged 30−39 years, 69.20% were females, 46.19% were university-educated, and 40.63% had one child. The overall Cronbach's alpha for the Arabic version of PACV was 0.799. The EFA of the 15 items showed that three domains were most conceptually equivalent. All items had a positive significant correlation with the mean score of each subscale except for item 4 (r = 0.016, p = 0.811). Regression analyses results indicated that education, previous COVID-19 infection, vaccine status of parents, and PACV score were significantly associated with the intention of the parents to vaccinate their children against COVID-19. The CFA results showed that most of the factor loadings were statistically significant (p < 0.010) except for items 4 and 7. However, the root mean square error of approximation (RMSEA = 0.080) and the standardized root mean squared residual (SRMR = 0.080) indicated that the model had a reasonable fit, and the three factors were good in reproducing each correlation. Our study results indicated the validity and reliability of the PACV instrument in Arabic language. Consequently, the PACV can be used to assess COVID-19 vaccine hesitancy in a majority of MENA countries for better delineation of this highly prevalent phenomenon in the region.

Degradable Glycopolyester-like Nanoparticles by Radical Ring-Opening Polymerization.

A small library of degradable polyester-like glycopolymers was successfully prepared by the combination of radical ring-opening copolymerization of 2-methylene-1,3-dioxepane as a cyclic ketene acetal (CKA) with vinyl ether (VE) derivatives and a Pd-catalyzed thioglycoconjugation. The resulting thioglycopolymers were formulated into self-stabilized thioglyconanoparticles, which were stable up to 4 months and were enzymatically degraded. Nanoparticles and their degradation products exhibited a good cytocompatibility on two healthy cell lines. Interactions between thioglyconanoparticles and lectins were investigated and highlighted the presence of both specific carbohydrate/lectin interactions and nonspecific hydrophobic interactions. Fluorescent thioglyconanoparticles were also prepared either by encapsulation of Nile red or by the functionalization of the polymer backbone with rhodamine B. Such nanoparticles were used to prove the cell internalization of the thioglyconanoparticles by lung adenocarcinoma (A549) cells, which underlined the great potential of P(CKA-co-VE) copolymers for biomedical applications.

Design, synthesis and biological evaluation of quinoline-2-carbonitrile-based hydroxamic acids as dual tubulin polymerization and histone deacetylases inhibitors.

A series of quinoline and quinazoline analogs were designed and synthesized as new tubulin polymerization (TP) and histone deacetylases (HDAC) inhibitors. Compounds 12a and 12d showed the best cytotoxicity activities against a panel of human cancer cell lines with an averaged IC50 value of 0.6 and 0.7 nM, respectively. Furthermore, these lead compounds showed good activities against CA-4-resistant colon-carcinoma and multidrug-resistant leukemia cells. In addition, compounds 12a and 12d induced HT29 cell cycle arrest in the G2/M phase and produced caspase-induced apoptosis of HT29 cells through mitochondrial dysfunction. Also, 12a and 12d inhibited HDAC8, 6, and 11 activities. Furthermore, lead compound 12a exhibited higher metabolic stability than isoCA-4 and was highly potent in suppressing tumor growth in the fibrosarcoma MCA205 tumor model. Collectively, these studies suggest that 12a represents a new dual inhibitor of TP and HDAC activities, which makes it a suitable candidate for further investigations in clinical development.

Experiences of Abused Muslim Women With the Australian Criminal Justice System.

The confidence of intimate partner violence (IPV) survivors/victims in the criminal justice system (CJS) is important to consider when exploring intervention and prevention strategies toward deterring IPV. Information on the experiences of IPV survivors/victims with the justice system is greatly lacking. This issue is even more so for IPV survivors/victims for minority communities such as Australian-Muslims. The lack of cultural and religious sensitivity that many immigrant women experience with the CJS deters them from accessing the CJS. In addition, the contrast between the mediation processes in courts and those of religious requirements may make the mediation processes ineffective if they do not include the perpetrators in the mediation process. Furthermore, for many migrant women, their lack of knowledge about their rights under the Australian legal system renders them powerless to undertake active action against IPV in their relationships. Due to the lack of research on Muslim women's experiences, it is difficult to ascertain how the justice system response can effectively address IPV issues for Australian Muslim women. It is therefore necessary to solicit Muslim women's views and explore past experiences with the justice system to inform future reforms that will better meet the justice response needs of Muslim women in Australia. This article explores Muslim women's positive and negative experiences with the justice system in response to their IPV victimization. It also investigates the constraints that have deterred Muslim women from seeking assistance from the Australian criminal justice system (ACJS), particularly in the reporting of intimate partner violence. The findings of this research give voice to Muslim women's past experiences with the CJS. It is expected that the findings will influence practical outcomes that can facilitate strategies by the CJS to promote inclusiveness among Muslim women to increase their confidence in the CJS.

Bee venom and its active component Melittin synergistically potentiate the anticancer effect of Sorafenib against HepG2 cells.

There are current attempts to find a safe substitute or adjuvant for Sorafenib (Sorf), the standard treatment for advanced hepatocellular carcinoma (HCC), as it triggers very harsh side effects and drug-resistance. The therapeutic properties of Bee Venom (BV) and its active component, Melittin (Mel), make them suitable candidates as potential anti-cancer agents per-se or as adjuvants for cancer chemotherapy. Hence, this study aimed to evaluate the combining effect of BV and Mel with Sorf on HepG2 cells and to investigate their molecular mechanisms of action. Docking between Mel and different tumor-markers was performed. The cytotoxicity of BV, Mel and Sorf on HepG2 and THLE-2 cells was conducted. Combinations of BV/Sorf and Mel/Sorf were performed in non-constant ratios on HepG2. Expression of major cancer-related genes and oxidative stress status was evaluated and the cell cycle was analyzed. The computational analysis showed that Mel can bind to and inhibit XIAP, Bcl2, MDM2, CDK2 and MMP12. Single treatments of BV, Mel and Sorf on HepG2 showed lower IC50than on THLE-2. All combinations revealed a synergistic effect at a combination index (CI) < 1. Significant upregulation (p < 0.05) of p53, Bax, Cas3, Cas7 and PTEN and significant downregulation (p < 0.05) of Bcl-2, Cyclin-D1, Rac1, Nf-κB, HIF-1a, VEGF and MMP9 were observed. The oxidative stress markers including MDA, SOD, CAT and GPx showed insignificant changes, while the cell cycle was arrested at G2/M phase. In conclusion, BV and Mel have a synergistic anticancer effect with Sorf on HepG2 that may represent a new enhancing strategy for HCC treatment.