This study aimsto optimize, characterize, and assess the phytosterol-loaded surface-tailored bioactive Alginate/Chitosan NPs for antitumor efficacy against breast cancer. β-Sitosterol-loaded Alginate/Chitosan nanoparticles (β-SIT-Alg/Ch-NPs) were fabricated using an ion-gelation technique, and then the NPs’ surfaces were activated using an EDC/sulfo-NHS conjugation reaction. The activated chitosan NPs werefunctionalized with folic acid (FA), leveled as β-SIT-Alg/Ch-NPs-FA. Moreover, the functionalized NPs were characterized for size distribution, polydispersity index (PDI), and surface charge, FT-IR and DSC. β-SIT released from β-SIT-Alg/Ch-NPs was estimated in various biorelevant media of pH 7.4, 6.5, and 5.5, and data werefitted into various kinetic models. The cytotoxic study of β-SIT-Alg/Ch-NPs-FA against the cancer cell line was established. The antioxidant study of developed β-SIT-Alg/Ch-NPs was performed using DPPH assay. The stability of developed optimized formulation was assessed in phosphate buffer saline (PBS, pH 7.4), as per ICH guidelines. The drug-entrapped Alg/Ch-NPs-FA appeared uniform and nonaggregated, and the nanoscale particle measured a mean size of 126 ± 8.70 nm. The %drug encapsulation efficiency and %drug loading in β-SIT-Alg/Ch-NPs-FA were 91.06 ± 2.6% and 6.0 ± 0.52%, respectively. The surface charge on β-SIT-Alg/Ch-NPs-FA was measured as +25 mV. The maximum β-SIT release from β-SIT-Alg/Ch-NPs-FA was 71.50 ± 6.5% in pH 5.5. The cytotoxic assay expressed an extremely significant antitumor effect by β-SIT-Alg/Ch-NPs-FA when compared to β-SIT-suspension (p < 0.001). The antioxidant capacity of β-SIT-Alg/Ch-NPs-FA was 91 ± 5.99% compared to 29 ± 8.02% for β-SIT-suspension. The stability of NPs noticed an unworthy alteration (p > 0.05) in particle sizes and other parameters under study in the specific period.

Background The kidneys are considered one of the most susceptible organs for adverse drug effects, particularly in post-transplant conditions. Tacrolimus (FK506), a calcineurin inhibitor immunosuppressant, is an essential component in the transplantation regimen. Despite that, nephrotoxicity is a severe drawback for its chronic utilization, where oxidative stress might be implicated. Kaempferol (KMF) is a natural flavonoid that has many adaptable biological activities, including antioxidant action. Objective Exploring the KMF protective effect on FK506-induced nephrotoxicity and the underlying role of calcineurin B1. Methods Twenty-four male albino-Wistar rats were randomly divided into three equal groups. The control group received solvents: propylene glycol, i.p. and 0.5% carboxymethyl cellulose, PO; FK506 group was injected with FK506 (0.6 mg/kg, i.p.), and FK506+KMF group was given FK506 (0.6 mg/kg, i.p.) and KMF (10 mg/kg, PO). The treatment regimen for all groups was once daily for 30 days. ELISA technique applied for measuring FK506 trough level and nephrotoxicity biomarkers in serum (cystatin C and urea) on days 15 and 30, and in kidney tissue homogenate (MDA and calcineurin B1) on day 30. Results In FK506-treated rats, the FK506 trough level was 7.84 ± 1.31 ug/l on day 15 and 9.54 ± 1.45 ug/l on day 30. FK506 use has significantly ( P <0.01) increased biomarkers levels of cystatin C (325% and 477%), urea (177% and 245%), MDA (1253%), except calcineurin B1 that has decreased (97%). The KMF combination has resulted in a significant reduction in the FK506 trough level by day 30 (6.79 ± 1.35 ug/l, P <0.01). KMF has significantly ameliorated the levels of cystatin C (46% and 73%, P <0.001), urea (38% and 68%, P< 0.001), MDA (75%, P <0.001), and calcineurin B1 (1833%, P <0.05). Conclusion Oxidative stress and calcineurin B1 are contributing factors in FK506-induced nephrotoxicity. Hence, inhibition of calcineurin enzyme is not limited to the immune cells. KMF could be a novel nephroprotective antioxidant.

The dental visits are a potentially valuable opportunity for screening patients with substance misuse and potentially assisting. However, it is not clear if there is a systematic approach in training general dental practitioners to gain competencies for screening and referral in such cases. We surveyed dental interns to learn about their readiness and understand their training on patients with substance misuse disorder. A 21-items questionnaire was formulated and then distributed among dental interns at KAUFD. The participants filled the questionnaire at the start of dental seminars organized by the intern office. A total of 130 interns completed the questionnaire. Drugs were perceived harmful and problematic in the region of 83% of participants. However, 52% of the participants did not believe that crimes were related to drug use. It was believed that most drugs have oral manifestations and dental practitioners should be trained to identify patients with SUD and modify the treatment plan accordingly. Participants believed that screening skills should be introduced to undergraduate students in their 4 th and 5 th years. Dentists reflect the understanding of the importance of addressing substance use however the competencies of screening and referrals are lacking in their training. Dealing with the global issue of drug abuse can be supported by including training as part of the curriculum and educating dental graduates and postgraduates on screening and basic interventions of patients with SUD.

Dyslipidemia is usually observed in both types of diabetes and, particularly, “atherogenic dyslipidemic triad” is strongly linked to a higher risk of adverse cardiovascular outcome. On the other hand, bone morphogenetic proteins (BMP) are a group of wide variety of proteins which were found overexpressed and implicated in contribution and acceleration of atherosclerotic calcification. So, the present study aimed to assess effect of DMH1, a selective BMP inhibitor, in a rat model of diabetic-induced dyslipidemia. Methods: STZ-induced diabetes in Wistar rats was used as a model to assess the antihyperlipidemic effect of DMH1(5mg/kg) for a period of 8 weeks. Rats were divided intonormal control (C=10), diabetic control (DC=10), diabetic+vehicle (DV=10) and diabetic DMH1-treated rats (DT=10). Fasting blood glucose (FBG) level was measured on weekly bases. Then, at the end of the experiment, rats were anesthetized and blood samples were collected for the determination of total cholesterol (TC), triglyceride (TG), LDL and HDL levels using the appropriate ELISA assay. Results: FBG levels for all diabetic groups were significantly high, during the experiment period, compared to the control (P< 0.001). While dyslipidemia was remarkable in the diabetic non-treated groups, DMH1 treatment showed a significant decrease in TC (P< 0.001), TG (P< 0.05) and LDL levels (P< 0.001) compared to the non-treated groups (DC & DV). Concurrently, HDL levels for DT group were significantly increased compared to DC or DV groups (P< 0.01). Conclusion: The present experiment showed that DMH1 possessed encouraging activityagainst dyslipidemia in STZ-induced diabetic rats. Our results are promoting for more interest and investigation regarding antihyperlipidemic effect of DMH1 and BMP/Smad pathway in further experimental studies.