Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression.

BACKGROUND: Electroconvulsive therapy (ECT) and subanesthetic intravenous ketamine are both currently used for treatment-resistant major depression, but the comparative effectiveness of the two treatments remains uncertain. METHODS: We conducted an open-label, randomized, noninferiority trial involving patients referred to ECT clinics for treatment-resistant major depression. Patients with treatment-resistant major depression without psychosis were recruited and assigned in a 1:1 ratio to receive ketamine or ECT. During an initial 3-week treatment phase, patients received either ECT three times per week or ketamine (0.5 mg per kilogram of body weight over 40 minutes) twice per week. The primary outcome was a response to treatment (i.e., a decrease of ≥50% from baseline in the score on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report; scores range from 0 to 27, with higher scores indicating greater depression). The noninferiority margin was -10 percentage points. Secondary outcomes included scores on memory tests and patient-reported quality of life. After the initial treatment phase, the patients who had a response were followed over a 6-month period. RESULTS: A total of 403 patients underwent randomization at five clinical sites; 200 patients were assigned to the ketamine group and 203 to the ECT group. After 38 patients had withdrawn before initiation of the assigned treatment, ketamine was administered to 195 patients and ECT to 170 patients. A total of 55.4% of the patients in the ketamine group and 41.2% of those in the ECT group had a response (difference, 14.2 percentage points; 95% confidence interval, 3.9 to 24.2; P<0.001 for the noninferiority of ketamine to ECT). ECT appeared to be associated with a decrease in memory recall after 3 weeks of treatment (mean [±SE] decrease in the T-score for delayed recall on the Hopkins Verbal Learning Test-Revised, -0.9±1.1 in the ketamine group vs. -9.7±1.2 in the ECT group; scores range from -300 to 200, with higher scores indicating better function) with gradual recovery during follow-up. Improvement in patient-reported quality-of-life was similar in the two trial groups. ECT was associated with musculoskeletal adverse effects, whereas ketamine was associated with dissociation. CONCLUSIONS: Ketamine was noninferior to ECT as therapy for treatment-resistant major depression without psychosis. (Funded by the Patient-Centered Outcomes Research Institute; ELEKT-D ClinicalTrials.gov number, NCT03113968.).

Evolving topological order in the postnatal visceral pleura.

BACKGROUND: Changes in epithelial cell shape reflects optimal cell packing and the minimization of surface free energy, but also cell-cell interactions, cell proliferation, and cytoskeletal rearrangements. RESULTS: Here, we studied the structure of the rat pleura in the first 15 days after birth. After pleural isolation and image segmentation, the analysis demonstrated a progression of epithelial order from postnatal day 1 (P1) to P15. The cells with the largest surface area and greatest shape variability were observed at P1. In contrast, the cells with the smallest surface area and most shape consistency were observed at P15. A comparison of polygonal cell geometries demonstrated progressive optimization with an increase in the number of hexagons (six-sided) as well as five-sided and seven-sided polygons. Analysis of the epithelial organization with Voronoi tessellations and graphlet motif frequencies demonstrated a developmental path strikingly distinct from mathematical and natural reference paths. Graph Theory analysis of cell connectivity demonstrated a progressive decrease in network heterogeneity and clustering coefficient from P1 to P15. CONCLUSIONS: We conclude that the rat pleura undergoes a striking change in pleural structure from P1 to P15. Further, a geometric and network-based approach can provide a quantitative characterization of these developmental changes.

Pharmacokinetics and cardiac safety of clofazimine in children with rifampicin-resistant tuberculosis.

Clofazimine is recommended for the treatment of rifampicin-resistant tuberculosis (RR-TB), but there is currently no verified dosing guideline for its use in children. There is only limited safety and no pharmacokinetic (PK) data available for children. We aimed to characterize clofazimine PK and its relationship with QT-interval prolongation in children. An observational cohort study of South African children <18 years old routinely treated for RR-TB with a clofazimine-containing regimen was analyzed. Clofazimine 100 mg gelatin capsules were given orally once daily (≥20 kg body weight), every second day (10 to <20 kg), or thrice weekly (<10 kg). PK sampling and electrocardiograms were completed pre-dose and at 1, 4, and 10 hours post-dose, and the population PK and Fridericia-corrected QT (QTcF) interval prolongation were characterized. Fifty-four children contributed both PK and QTcF data, with a median age (2.5th-97.5th centiles) of 3.3 (0.5-15.6) years; five children were living with HIV. Weekly area under the time-concentration curve at steady state was 79.1 (15.0-271) mg.h/L compared to an adult target of 60.9 (56.0-66.6) mg.h/L. Children living with HIV had four times higher clearance compared to those without. No child had a QTcF ≥500 ms. A linear concentration-QTcF relationship was found, with a drug effect of 0.05 (0.027, 0.075) ms/µg/L. In some of the first PK data in children, we found clofazimine exposure using an off-label dosing strategy was higher in children versus adults. Clofazimine concentrations were associated with an increase in QTcF, but severe prolongation was not observed. More data are required to inform dosing strategies in children.

Economic costs of obesity: a systematic review.

INTRODUCTION: Obesity is a growing public health problem leading to substantial economic impact. This study aimed to summarize the economic impact of obesity and to critically analyze the methods used in the cost-of-illness (COI) studies on obesity. METHODS: We conducted systematic search in PubMed and Scopus from September 1, 2016, to July 22, 2022. Original COI studies estimating the economic cost of obesity and/or overweight in at least one country, published in English were included. To facilitate the comparison of estimates across countries, we converted the cost estimates of different years to 2022 purchasing power parity (PPP) values using each country's consumer price index (CPI) and PPP conversion rate. RESULTS: Nineteen studies were included. All studies employed a prevalence-based approach using Population Attributable Fraction (PAF) methodology. About half of the included studies (53%) were conducted in high-income countries while the others (47%) were conducted in middle-income countries. The economic burden of obesity ranged between PPP 15 million in Brazil to PPP 126 billion in the USA, in the year 2022. Direct medical costs accounted for 0.7% to 17.8% of the health system expenditure. Furthermore, the total costs of obesity ranged from 0.05% to 2.42% of the country's gross domestic product (GDP). Of the seven studies that estimated both direct and indirect costs, indirect costs accounted for the largest portion of five studies. Nevertheless, a variety in methodology across studies was identified. The number of co-morbidities included in the analysis varied across studies. CONCLUSIONS: Although there was a variety of methodologies across studies, consistent evidence indicated that the economic burden of obesity was substantial. Obesity prevention and control should be a public health priority, especially among countries with high prevalence of obesity.

The effect of an anti-malarial herbal remedy, Maytenus senegalensis, on electrocardiograms of healthy Tanzanian volunteers.

BACKGROUND: The emergence of resistance to artemisinin-based combination therapy necessitates the search for new, more potent antiplasmodial compounds, including herbal remedies. The whole extract of Maytenus senegalensis has been scientifically investigated for potential biological activities both in vitro and in vivo, demonstrating strong antimalarial activity. However, there is a lack of data on the electrocardiographic effects of M. senegalensis in humans, which is a crucial aspect in the investigation of malaria treatment. Assessing the electrocardiographic effects of M. senegalensis is essential, as many anti-malarial drugs can inadvertently prolong the QT interval on electrocardiograms. Therefore, the study's objective was to evaluate the electrocardiographic effects of M. senegalensis in healthy adult volunteers. METHODS: This study is a secondary analysis of an open-label single-arm dose escalation. Twelve healthy eligible Tanzanian males, aged 18 to 45, were enrolled in four study dose groups. A single 12-lead electrocardiogram (ECG) was performed at baseline and on days 3, 7, 14, 28, and 56. RESULTS: No QTcF adverse events occurred with any drug dose. Only one volunteer who received the highest dose (800 mg) of M. senegalensis experienced a moderate transient change (△QTcF > 30 ms; specifically, the value was 37 ms) from baseline on day 28. There was no difference in maximum QTcF and maximum △QTcF between volunteers in all four study dose groups. CONCLUSIONS: A four-day regimen of 800 mg every 8 h of M. senegalensis did not impact the electrocardiographic parameters in healthy volunteers. This study suggests that M. senegalensis could be a valuable addition to malaria treatment, providing a safer alternative and potentially aiding in the battle against artemisinin-resistant malaria. The results of this study support both the traditional use and the modern therapeutic potential of M. senegalensis. They also set the stage for future research involving larger and more diverse populations to explore the safety profile of M. senegalensis in different demographic groups. This is especially important considering the potential use of M. senegalensis as a therapeutic agent and its widespread utilization as traditional medicine. Trial registration ClinicalTrials.gov, NCT04944966. Registered 30 June 2021-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04944966?term=kamaka&draw=2&rank=1.

Improved Durability to SARS-CoV-2 Vaccine Immunity following Coimmunization with Molecular Adjuvant Adenosine Deaminase-1.

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have demonstrated strong immunogenicity and protection against severe disease, concerns about the duration and breadth of these responses remain. In this study, we show that codelivery of plasmid-encoded adenosine deaminase-1 (pADA) with SARS-CoV-2 spike glycoprotein DNA enhances immune memory and durability in vivo. Coimmunized mice displayed increased spike-specific IgG of higher affinity and neutralizing capacity as compared with plasmid-encoded spike-only-immunized animals. Importantly, pADA significantly improved the longevity of these enhanced responses in vivo. This coincided with durable increases in frequencies of plasmablasts, receptor-binding domain-specific memory B cells, and SARS-CoV-2-specific T follicular helper cells. Increased spike-specific T cell polyfunctionality was also observed. Notably, animals coimmunized with pADA had significantly reduced viral loads compared with their nonadjuvanted counterparts in a SARS-CoV-2 infection model. These data suggest that pADA enhances immune memory and durability and supports further translational studies.

Consensus-Based Expert Recommendations on the Management of Hemophilia A in the Gulf Region.

BACKGROUND: Hemophilia A presents a significant health challenge in the Gulf region, where it has an especially high prevalence. There are several unmet needs associated with the management of hemophilia A in the region. The aim of this manuscript was to contextualize unmet management needs, provide recommendations to optimize care, and specify requirements for the establishment of gene therapy centers in the region. SUMMARY: An expert panel was assembled comprising ten clinical hematologists from Kuwait, Oman, Saudi Arabia, and the UAE. The Delphi methodology was used to obtain a consensus on statements relating to several aspects of hemophilia A. A consensus was reached for all statements by means of an online, anonymized voting system. The consensus statements pertain to screening and diagnosis, treatment approaches, and requirements for the implementation of gene therapy. KEY MESSAGES: There are significant challenges that hinder the optimal management of hemophilia A in the Gulf region. The consensus statements presented provide specific recommendations to improve diagnostic and treatment approaches, promote multidisciplinary care, and optimize regional data generation and reporting. These statements also delineate the requirements for the establishment of gene therapy centers for hemophilia A in the region.

Novel guanidine derivatives targeting leukemia as selective Src/Abl dual inhibitors: Design, synthesis and anti-proliferative activity.

A new series of benzene-sulfonamide derivatives 3a-i was designed and synthesized via the reaction of N-(pyrimidin-2-yl)cyanamides 1a-i with sulfamethazine sodium salt 2 as dual Src/Abl inhibitors. Spectral data IR, 1H-, 13C- NMR and elemental analyses were used to confirm the structures of all the newly synthesized compounds 3a-i and 4a-i. Crucially, we screened all the synthesized compounds 3a-i against NCI 60 cancer cell lines. Among all, compound 3b was the most potent, with IC50 of 0.018 µM for normoxia, and 0.001 µM for hypoxia, compared to staurosporine against HL-60 leukemia cell line. To verify the selectivity of this derivative, it was assessed against a panel of tyrosine kinase EGFR, VEGFR-2, B-raf, ERK, CK1, p38-MAPK, Src and Abl enzymes. Results revealed that compound 3b can effectively and selectively inhibit Src/Abl with IC500.25 µM and Abl inhibitory activity with IC500.08 µM, respectively, and was found to be more potent on these enzymes than other kinases that showed the following results: EGFR IC500.31 µM, VEGFR-2 IC500.68 µM, B-raf IC500.33 µM, ERK IC501.41 µM, CK1 IC500.29 µM and p38-MAPK IC500.38 µM. Moreover, cell cycle analysis and apoptosis performed to compound 3b against HL-60 suggesting its antiproliferative activity through Src/Abl inhibition. Finally, molecular docking studies and physicochemical properties prediction for compounds 3b, 3c, and 3 h were carried out to investigate their biological activities and clarify their bioavailability.

Supporting social emotional learning and wellbeing of displaced adolescents from the middle east: a pilot evaluation of the 'forward with peers' intervention.

BACKGROUND: A growing literature points to the critical role schools can play in promoting improved psychosocial wellbeing and resilience among first- and second-generation Arab immigrant and refugee adolescents, but few evaluations have examined the effectiveness of culturally adapted, school-based interventions. METHODS: We conducted a pilot evaluation of a culturally adapted social and emotional learning and life skills program, Forward with Peers (FwP), and examined its potential effectiveness for this population. FwP was evaluated across three high schools in the Detroit Metropolitan Area. Within each school, one Arabic class was randomly assigned to receive FwP programming and another served as a control. The pilot evaluation sought to examine changes in several mental health and psychosocial outcomes of interest. FINDINGS: Improvements in overall perceived social support (P = 0.045) and perceived social support from someone special in one's life (0.042) were statistically significant in the treatment as compared to the control group. Comparative improvements were also marginally significant for resilience (P = 0.095) and perceived social support from family (P = 0.074). CONCLUSIONS: Findings highlight the potential of FwP and support the growing interest in establishing efficacy of school-based, culturally appropriate SEL programming to improve psychosocial wellbeing among Arab refugee and immigrant adolescents. FwP's demonstrated improvements in resilience and social support have the potential to prevent mental health disorders and bolster coping mechanisms to minimize adverse consequences in this vulnerable population. Employing a strengths-based approach, FwP offers an alternative intervention to traditional treatment-oriented supports for the proliferation of mental health disorders within this vulnerable population.

Design, spectroscopic characterizations, and biological investigation of oxospiro[chromine-4,3-indolene]-based compounds as promising antiproliferative EGFR inhibitors and antimicrobial agents.

Utilizing microwave heating and an aqueous saturated solution of K2CO3 as a catalyst, a rapidone-pot synthesis of oxospiro[chromene-4.3-indoline] derivatives was produced in high yields. The experimental results confirmed that the saturated solution of K2CO3 gives outstanding yield to dangerous metals and strong bases during investigations into high-performance catalysts. The used catalyst is green, affordable, incredibly mild, and widely accessible. However, it generates samples, reduces the amount of byproducts, and is expected to be used in industrial-scale heterocyclic derivatives. New oxospiro[chromene-4.3-indoline] derivatives have been created from various isatin by condensing with various phenols. The biological activities results showed that when compared to erlotinib, the derivatives 3b, 4b, 5b, and 6b were the most effective analogues on A549, MCF-7, HepG-2, and HCT-116 cells, with an IC50 range of 3.32 to 11.88 µM. In A549 cells, compounds 3b, 4b, 5b, and 6b induced apoptosis, as shown by the up-regulation of Bax, the up-regulation of Bcl-2, and the stimulation of caspase-3 and -9. With IC50 value of 0.19 ± 0.09, compound3b was demonstrated to be the most effective against EGFRWT. Compounds 4b and 6b have good antibacterial activity toward Staphylococcus aureus, comparable to ciprofloxacin, and about half as much activity as ampicillin, according to the MIC value. Compound 6b's MIC is about 25% lower than clotrimazole drug. The in silico molecular docking outcomes of compounds 3b, 4b, 5b, and 6b in the EGFR active site depicted their ability to adopt essential binding interactions compared to the reference Erlotinib. Moreover, the investigation of the physicochemical properties of the most promising dual acting antiproliferative and antimicrobial compounds 4b and 6b through the egg-boiled method illustrated acceptable lipophilicity, GIT absorption, and blood-brain barrier penetration characteristics.

Efficacy and safety of calcipotriol as a potential topical treatment of acne vulgaris: a randomized, controlled, triple blinded, split-face clinical trial.

BACKGROUND: Acne vulgaris is a common skin problem that may result in significant scarring and systemic comorbidities. Adverse effects and increasing resistance to available treatments urge the development of new therapeutics. Topical vitamin D analogues have been successfully used in psoriasis; however, the efficacy and safety of calcipotriol as a potential topical treatment of acne is yet to be established. OBJECTIVES: To evaluate the efficacy and safety of calcipotriol in treating acne compared with adapalene and placebo. METHODS: Sixty patients with acne were included and randomly divided into two groups of 30 patients each. Group I participants were treated by daily application of calcipotriol 0.005% cream on one facial side vs. placebo (petrolatum) over the other side. Group II were treated by daily application of adapalene 0.1% gel over one facial side vs. calcipotriol on the other. Therapeutic response was evaluated using the Japanese Acne Grading System (JAGS) and through photographic evaluation using Mean Improvement Score by Physician. RESULTS: Adapalene-treated skin gave the greatest improvement and the highest patient satisfaction compared with skin treated with calcipotriol or placebo (P = 0.001). Nonetheless, the calcipotriol-treated side showed a significantly greater reduction in post-treatment JAGS score and much greater satisfaction than placebo. As treatment continued, improved tolerability to calcipotriol was noted, with comparable side-effects between the three study arms. CONCLUSIONS: Calcipotriol seems to be a promising new safe topical therapeutic option for acne. However, adapalene is still superior in efficacy, tolerability and patient satisfaction.

Contraindications to tissue plasminogen activator thrombolysis for acute lower extremity ischemia.

OBJECTIVE: Previous randomized prospective trials have demonstrated the effectiveness of transcatheter tissue plasminogen activator (tPA) thrombolysis in treating acute limb ischemia (ALI) compared to conventional surgery. These pivotal trials have also highlighted contraindications for these procedures. Given recent advancements in techniques and technology, our aim is to reassess the relevance of these contraindications in contemporary practice. METHODS: A retrospective chart analysis was performed utilizing the inpatient medical records of consecutive individuals who underwent tPA treatment for acute limb ischemia (ALI) from September 2016 to April 2022. Inclusion criteria encompassed patients aged 18 and above displaying clinical symptoms and imaging evidence of ALI within 14 days. All patients received tPA with suction thrombectomy following the fast-track thrombolysis protocol. In cases where a persistent thrombus or stenosis was detected, catheter-directed thrombolysis was considered overnight, and patients underwent angiography and reassessment in the operating room subsequently. RESULTS: Patients were classified into two groups based on the STILE trial's established contraindications for endovascular treatment in acute limb ischemia (ALI). If a patient had any of these contraindications, they were placed in the contraindicated group. This resulted in 24 patients (32%) in the contraindicated group and 52 patients (68%) in the non-contraindicated group. No statistically significant demographic variations were observed between these groups. Contraindications in our study included uncontrolled hypertension (12/24, 50%), recent invasive procedures (7/27, 29%), history of cerebrovascular accident (CVA) within 6 months (3/24, 12%), and intracranial malformation/neoplasms (2/24, 8%). Three patients within the non-contraindicated group experienced bleeding complications: two with puncture site bleeds and one with nasal bleeding. In contrast, one patient in the contraindicated group had transient postoperative hematuria. There were no significant differences in bleeding complications observed between the two groups (p = .771). Additionally, no amputations were observed within our population. CONCLUSIONS: In light of our study results and advancements in endovascular therapies, we can now safely and efficiently treat patients who were previously considered contraindicated for such treatments. It is essential to individualize treatments and carefully balance the risks and benefits of endovascular versus open surgical revascularization for these patients. Additionally, we believe that the nearly 30-year-old guidelines for endovascular therapies need to be revisited and updated to align with modern technology.

Molecular docking studies on α-amylase inhibitory peptides from milk of different farm animals.

Milk-derived peptides have emerged as a popular mean to manage various lifestyle disorders such as diabetes. Fermentation is being explored as one of the faster and efficient way of producing peptides with antidiabetic potential. Therefore, in this study, an attempt was made to comparatively investigate the pancreatic α-amylase (PAA) inhibitory properties of peptides derived from milk of different farm animals through probiotic fermentation. Peptide's identification was carried out using liquid chromatography-quadrupole time-of-flight mass spectrometry and inhibition mechanisms were characterized by molecular docking. Results obtained showed a PAA-IC50 value (the amount of protein equivalent needed to inhibit 50% of enzymes) between 2.39 and 36.1 µg protein equivalent for different fermented samples. Overall, Pediococcus pentosaceus MF000957-derived fermented milk from all animals indicated higher PAA inhibition than other probiotic derived fermented milk (PAA-IC50 values of 6.01, 3.53, 15.6, and 10.8 µg protein equivalent for bovine, camel, goat, and sheep fermented milk). Further, molecular docking analysis indicated that camel milk-derived peptide IMEQQQTEDEQQDK and goat milk-derived peptide DQHQKAMKPWTQPK were the most potent PAA inhibitory peptides. Overall, the study concluded that fermentation derived peptides may prove useful in for managing diabetes via inhibition of carbohydrate digesting enzyme PAA.

Design, Characterization and SAR Studies of Novel Bioactive Benzylideneacetophenone Derivatives as Insecticidal Agents against Spodoptera frugiperda (Lepidoptera: Noctuidae).

Unintentional environmental effects brought on by insecticides encourage the creation of safer substitutes. A very polyphagous migrating lepidopteran pest species in Africa called S. Frugiperda causes terrible damage. In the current paper, treatment of 4-acetylphenyl 4-methylbenzenesulfonate with different aromatic aldehydes in the presence of NaOH afforded benzylideneacetophenones. The structure of the newly prepared compounds were proved by different spectroscopic techniques such as IR, 1 H-NMR, 13 C NMR, and elemental analysis. We looked at the association between contact with S. frugiperda and stricture reaction to examine their harmful effect. Additionally, S. frugiperda was used for testing the newly created compounds for their ability to kill insects. The majority of substances have been proven to be effective and promising. It has been found that 4-[3-(4-Methylphenyl)prop-2-enoyl]phenyl-4-methyl benzenesulfonate (4) was the most active with an LC50 =3.46 mg/L of 2nd instar larvae and LC50 =9.45 mg/L of 4th instar larvae. Moreover, some of biological and histopathological aspects of the synthesized products were investigated under laboratory conditions.

Exploring the Antiproliferative Potency of Pyrido[2,3-d]Pyrimidine Derivatives: Studies on Design, Synthesis, Anticancer Evaluation, SAR, Docking, and DFT Calculations.

Herein, an efficient method for the synthesis of a new series of pyrido[2,3-d]pyrimidine derivatives has been adopted through the reaction of hydrazinyl pyrido[2,3-d] pyrimidine derivative (1) with different electrophilic species, such as ethyl cyanoacetate and different 1,3 diketone derivatives, gave the corresponding derivatives (2-5). Meanwhile, pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidines (6-11) were synthesized via reaction of hydrazine derivative 1 with phenylisothiocyanate, potassium thiocyanate, and carbon disulfide. Compound 1 was also submitted to react with different carbonyl compounds to afford pyrido-pyrimidine derivatives (12-15). All the newly synthesized compounds were tested in vitro for their antiproliferative activities against HCT-116 and MCF-7 cell lines. Compounds 2, 3, 7, and 8 displayed very strong inhibitory activity against the two cell lines compared with the standard drug doxorubicin. Furthermore, a docking study of the most active compounds was performed with the thymidylate synthase enzyme (PDB: Code 6qxg). Moreover, DFT calculation was carried out for the most biologically active compounds and a reference drug (Doxorubicin) using the B3LYP/6-31G+(d,p) level of theory. The calculated EHOMO and ELUMO energies were used to calculate the global reactivity parameters. Finally, Molecular electrostatic potential (MEP) and structure activity relationship (SAR) were studied to correlate the relation between chemical structure and reactivity.

Pharmacophore-based, rationale design, and efficient synthesis of novel tetrahydrobenzo[b]thiophene candidates as potential dual Topo I/II inhibitors and DNA intercalators.

A series of tetrahydrobenzo[b]thiophene derivatives was designed and synthesized as dual topoisomerase (Topo) I/II inhibitors implicating potential DNA intercalation. Ethyl-2-amino-3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene-4-carboxylate (1) was prepared by modification of the Gewald reaction procedure using a Fe2O3 nanocatalyst and then it was used as a building block for the synthesis of tetrahydrobenzo[b]thiophene candidates (2-14). Interestingly, compound 14 showed the best cytotoxic potential against hepatocellular, colorectal, and breast cancer cell lines (IC50 = 7.79, 8.10, and 3.53 µM), respectively, surpassing doxorubicin at breast cancer (IC50 = 4.17 µM). Meanwhile, the Topo I and II inhibition assay displayed that compound 3 could exhibit the best inhibitory potential among the investigated candidates (IC50 = 25.26 and 10.01 nM), respectively, in comparison to camptothecin (IC50 = 28.34 nM) and doxorubicin (IC50 = 11.01 nM), as reference standards. In addition, the DNA intercalation assay showed that compound 14 could display the best binding affinity with an IC50 value of 77.82 µM in comparison to doxorubicin (IC50 = 58.03 µM). Furthermore, cell cycle and apoptosis analyses described that compound 3 prompts the G1 phase arrest in michigan cancer foundation-7 cancer cells and increases the apoptosis ratio by 29.31% with respect to untreated cells (2.25%). Additionally, the conducted molecular docking assured the promising binding of the investigated members toward Topo I and II with potential DNA intercalation. Accordingly, the synthesized compounds could be treated as promising anticancer candidates for future optimization.

Potential effects of probiotics (immunobacteryne; IMB) on growth performance, feed efficacy, blood biochemical, redox balance, nonspecific immunity and heat-shock protein expression of Nile tilapia (Oreochromis niloticus) fingerlings.

The supplementation of aquafeed with probiotics is recommended for feasible aquaculture activities. Therefore, the aim of current study was to investigate the potential effects of probiotics on growth performance, feed utilization, biochemical attributes, redox status and immunity response as well as the transcription of heat-shock protein 70 (HSP70) and insulin-like growth factor-1 (IGF-1) genes of Nile tilapia (Oreochromis niloticus; n = 120). Fish with an initial weight of 8.17 ± 0.02 g/fish were randomly divided into four treatment groups and were fed diets containing 0, 0.5, 1 and 1.5 mg immunobacteryne (IMB)/kg diet respectively. Dietary IMB at 1.5 g/kg diet significantly improved the growth performance, feed consumption and growth hormone secretion of the experimental fish (p < 0.05). The 1 or 1.5 g IMB/kg diet boosted phagocytic activities and innate immune response. Serum total protein, total cholesterol, triglycerides and glucose were significantly increased in the groups that were fed 1 and 1.5 mg IMB/kg diet compared to the control (p < 0.05). Meanwhile, the levels of uric acid, creatinine, liver enzymes (aspartate transaminase and alanine transaminase) and cortisol hormone were significantly reduced in the aforementioned treated groups compared to the control (p < 0.05). All fish fed IMB-supplemented diet showed a significant increase in the expression of IGF-1 gene, while the transcription of HSP70 was significantly decreased (p < 0.05). In conclusion, the dietary inclusion of IMB (1 g/kg diet) enhanced growth promoters, feed efficacy, blood biochemical, redox balance and nonspecific immune responses in Nile tilapia fingerlings.

Investigating the impact of nanoemulsion of curcumin-loaded olive oil on growth performance, feed utilization, immunological responses, and redox status of Litopenaeus vannamei shrimp with emphasis on economic efficiency of supplementation.

The trail aimed to explore the effect of dietary supplementation of curcumin loaded olive oil nanoemulsion (CUR-OLNE) on growth performance, feed utilization, blood biochemical, redox status, and immune response of Litopenaeus vannamei shrimp, considering the economic efficiency of supplementation. A total of 280 healthy shrimps (3.42 ± 0.02 g) were randomly distributed into five equal groups and were fed diets containing 0 (CUR-OLNE0), 5(CUR-OLNE5), 10(CUR-OLNE10), 15(CUR-OLNE15) and 20 (CUR-OLNE20) mg CUR-OLNE/kg diet, respectively for 16 weeks. Among CUR-OLNE treated groups, CUR-OLNE20 showed the highest growth performance and feed utilization traits, including final body weight, specific growth rate, feed conversion ratio, and protein efficiency ratio. Notably, the photomicrographs provided further compelling evidence regarding the potential effect of CUR-OLNE supplementation on muscle structure and integrity. Compared to the control, the levels of blood protein significantly induced in CUR-OLNE15 and CUR-OLNE20 treated groups (p < 0.05). All CUR-OLNE -supplemented groups possessed lower activities of liver enzymes as well as the levels of urea and creatinine compared to the control (p < 0.05). The addition of 20 mg CUR-OLNE/kg diet decreased the concentrations of cortisol, glucose and triglycerides. The dietary treatment significantly improved the secretion of digestive enzymes, including amylase, lipase, and protease. The lowest levels of Malondialdehyde and the highest levels of total antioxidant capacity, super oxide dismutase, catalase, lysozyme and immunoglobulin M were detected in both of CUR-OLNE15, and CUR-OLNE20 treated groups compared to the control (p < 0.05). There were considerable significant effects of dietary supplementation of CUR-OLNE on economic efficiency. In conclusion, the application of nanocarriers for the delivery of dietary immune stimulants such as CUR-OLNE to Litopenaeus vannamei shrimp is a promising strategy for improving shrimp nutrition. The addition of 20 mg CUR-OLNE/kg to the diets of can be recommended as an affective intervention to improve growth performance, feed utilization, and health status of shrimp. Implementing this intervention can maximize the economic efficiency of shrimp farming while promoting sustainable practices in the industry.

Feasible feeding strategies for sustainable management of serve heat stress conditions: Effect of Milk Thistle extract on growth performance and health status of newly weaned rabbits.

The trail aimed to explore the effect of dietary supplementation of Milk Thistle (MT) extract on growth performance and health status of growing rabbits exposed to serve heat stress condition, considering the economic efficiency of supplementation. A total of 96 weaned male rabbits were divided into 4 groups (24 rabbits/group). The first group received the basal diet without any supplementation and served as a control (MT0), while 2nd, 3rd and 4th groups supplemented with MT at levels of 5 (MT5), 10 (MT10) and 15 (MT15) g/kg diet, respectively, for 10 consecutive weeks. Both of growth performance and feed utilisation were significantly enhanced by the dietary treatment, the optimum dose of MT was 12 g/kg diet for average daily gain, specific growth rate and performance index. However, it was 13 g/kg diet for feed conversation ratio. The polynomial regression analysis showed that the lowest values of rectal temperature and respiration rate were observed at doses of 11 and 13 g/kg diet respectively. The dressing percentage and the relative weights of liver and total edible giblets were significantly improved by the treatment (p = 0.0416, 0.0112 and 0.0032, respectively), maximising in the MT10 group. The MT10 and MT15 groups showed higher erythrocytes and leucocytes counts and lower levels of urea, creatinine and total cholesterol compared to the control (p < 0.05). Liver functions significantly enhanced in aforementioned two treated groups, the liver ultrastructure represented normal cytoplasmic organelles, and nucleus and mitochondria in MT10 group, while the MT15 group showed hepatocytes with dilated nucleus with most cytoplasmic organelles appeared well organised and normal except few small cytoplasms vacuolated. The levels glutathione, superoxide dismutase, catalase and total antioxidant capacity as well as immunoglobulin M, and immunoglobulin G significant improved in the MT-Treated groups compared to the control (p < 0.05). Economically, MT supplemented diets improved the net revenue of fattened rabbits during the summer season. In conclusion, the supplementation of MT extract at levels of 10 or 15 g/kg diet enhanced growth performance, feed utilisation, dressing percentage, hemato-biochemical attributes, immunity and redox balance of heat stressed growing rabbits during the hot season.

Salinity-induced desertification in oasis ecosystems: challenges and future directions.

Salinity-induced desertification is a pressing environmental issue that poses a significant threat to the sustainability of oasis ecosystems worldwide. These ecosystems are vital to the livelihoods of millions of people living in hyper-arid, arid and semi-arid regions, providing essential resources such as food, water and other necessities. However, overexploitation of natural resources, changes in land use and climate change have led to the degradation of these ecosystems, resulting in soil salinisation, waterlogging and other adverse effects. Combating salinity-induced desertification requires a comprehensive approach that addresses both the underlying causes of ecosystem degradation and the direct consequences for local communities. The strategy may include measures for sustainable land use, reforestation and water conservation. It is also essential to involve local communities in these activities and to ensure that their perspectives are heard. The aim of this article is to examine the causes and processes of salinity-induced desertification in oasis ecosystems and the implications for their sustainability. It also examines strategies that are being used to prevent desertification and promote sustainable oasis management. This article aims to raise awareness of this critical issue and to promote action towards a more sustainable future.