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In the field of healthcare logistics, the reliance on conventional transport methods such as cars for the delivery of monoclonal antibodies (mAbs) is susceptible to challenges posed by traffic and infrastructure, leading to increased and unpredictable transport times. Recognizing the potential role of drones in mitigating these challenges, we aimed to investigate the impact of medical drone transport on the stability of mAbs. Compromised stability could lead to aggregation and immunogenicity, thereby jeopardizing the efficacy and safety of mAbs. We studied the transportation of vials as well as ready-to-administer infusion bags with blinatumomab, tocilizumab, and daratumumab. The methodology involved the measurement of both temperature and mechanical shock during drone transport. Moreover, the analytical techniques High Performance Size-Exclusion Chromatography (HP-SEC), Dynamic Light Scattering (DLS), Light Obscuration (LO), Micro-Flow Imaging (MFI), and Nanoparticle Tracking Analysis (NTA) were employed to comprehensively assess the presence of aggregates and particle formation. The key findings revealed no significant differences between car and drone transport, indicating that the stability of mAbs in both vials and infusion bags was adequately maintained during drone transport. This suggests that medical drones are a viable and reliable means for the inter-hospital transport of mAbs, paving the way for more efficient and predictable logistics in healthcare delivery. [ABSTRACT FROM AUTHOR]

Purpose: It has been debated whether the Le Fort III procedure using distraction osteogenesis (LFIII-DO) reduces the risk of postintervention relapse compared with conventional Le Fort III (LFIII) osteotomy in the correction of syndromic midfacial hypoplasia. Our objective was to evaluate the short- and long-term stability of the bony structures after midfacial advancement using conventional LFIII osteotomy versus LFIII-DO in patients with syndromic midfacial hypoplasia. Materials and Methods: We performed a systematic review of the published data. An electronic search of 10 databases was performed from their inception through June 2012. The reference lists of the relevant publications were also reviewed. Studies were considered for inclusion if they were longitudinal clinical studies with follow-up periods of at least 1 year after surgery (LFIII group) or at the end of the consolidation period (LFIII-DO group). Study selection, risk of bias assessment, and data extraction were performed in duplicate. The methodologic and clinical heterogeneity across the studies precluded combining the findings using meta-analyses. Results: A total of 57 reports met the initial search criteria, and 12 reports were finally selected. The studies demonstrated a mean midfacial advancement of 8 to 12 mm in the LFIII group and 9 to 16 mm in the LFIII-DO group. For the LFIII group, horizontal short-term follow-up showed a maximal rate of relapse of 8.7 to 11.9% in 2 studies, with 1 study demonstrating a far more severe rate of maximal relapse of 50%. For the LFIII-DO procedure, the horizontal short-term relapse rate was 14.4% in 1 study, with the remainder demonstrating a rate of relapse of less than 10%. Moreover, 3 studies even showed additional advancement without any rate of relapse. Conclusions: Current evidence suggests that conventional LFIII and LFIII-DO techniques can effectively advance the midface forward in patients with syndromic midfacial hypoplasia and have good to excellent stability, with a mild rate of relapse. However, the LFIII-DO technique appears to achieve a greater amount of advancement with a lower rate of relapse compared with the conventional LFIII technique. [ABSTRACT FROM AUTHOR]

Hydroxytyrosol (HYT) is one of the main alcoholic compounds of the olive leaves extract (OLE), which is known for its beneficial effects. This study aimed to investigate the effectiveness of olive leaves extract standardized with 25% hydroxytyrosol (OLES-25%HYT) in treatment of induced ulcerative colitis. Three groups of albino rats, were divided as following, group 1 (normal control), group 2 (induced ulcerative colitis and untreated) and group 3 (induced ulcerative colitis and treated with OLES-25%HYT). Colonic tissue samples were collected from all studied groups, the antioxidant activity for malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), myeloperoxidase (MPO) and nitric oxide (NO) were performed. The expression of pro-inflammatory cytokines, the apoptotic gene Bax and the anti-apoptotic gene Bcl2 was obtained in colon tissue to evaluate the OLES-25%HYT effect on ulcerative colitis. OLES-25%HYT showed effectiveness on reduction of mortality rate and disease activity index (DAI). Also, reduced oxidative stress and inflammation in colon tissue, OLES-25%HYT showed a significant reduction in colon MDA, MPO and NO levels and a significant elevation in SOD, CAT and GPX levels and cause down regulation of pro-inflammatory cytokines. Also, the apoptotic gene Bax downregulated and the anti-apoptotic gene Bcl2 upregulated as a result of the treatment compared to untreated induced ulcerative colitis group. OLES-25%HYT showed intestinal anti-inflammatory, antioxidants and anti-apoptotic effects in experimental models of ulcerative colitis. [Display omitted] • Ulcerative colitis consider one of the major inflammatory bowel disease. • Hydroxytyrosol is a phenolic alcohol, with wide range of biological effects • Hydroxytyrosol ameliorate oxidative biomarkers in ulcerative colitis • Hydroxytyrosol reduce inflammatory biomarkers in ulcerative colitis [ABSTRACT FROM AUTHOR]

• The wide functionality of CDK12 in a cell-specific manner. • Rationale for using CDK12 as a biomarker and therapeutic target. • Structural dissection of CDK12 associated with its biological roles. • Challenges and strategies to develop potent and selective CDK12 inhibitors. Cyclin-dependent kinase (CDK) 12 engages in diversified biological functions, from transcription, post-transcriptional modification, cell cycle, and translation to cellular proliferation. Moreover, it regulates the expression of cancer-related genes involved in DNA damage response (DDR) and replication, which are responsible for maintaining genomic stability. CDK12 emerges as an oncogene or tumor suppressor in different cellular contexts, where its dysregulation results in tumorigenesis. Current CDK12 inhibitors are nonselective, which impedes the process of pharmacological target validation and drug development. Herein, we discuss the latest understanding of the biological roles of CDK12 in cancers and provide molecular analyses of CDK12 inhibitors to guide the rational design of selective inhibitors. [ABSTRACT FROM AUTHOR]

The discovery of novel anti-AML therapeutic agents is urgently needed, but the complex heterogeneity of the disease has so far hampered the development of a curative treatment. FLT3 inhibitors have shown therapeutic potential in clinical trials; but a monotherapy regimen has been associated with resistance mediated by the activation of parallel signalling circuitry, including MAPK and mTOR. Therefore, inhibiting a nexus of the two signalling pathways along with inhibition of FLT3 might be advantageous. Herein, we propose that a dual inhibition of FLT3 and Mnk would provide a better clinical option for AML patients compared to targeting FLT3 alone. Thus, a series of N -phenyl-4-(thiazol-5-yl)pyrimidin-2-amines and 4-(indol-3-yl)- N -phenylpyrimidin-2-amines were prepared. Potent Mnk2 inhibitors, FLT3 inhibitors, and dual inhibitors of Mnk2 and FLT3 were identified and their anti-proliferative activities assessed against MV4-11 AML cell lines. Dual inhibition of FLT3 and Mnk2 caused the increased apoptotic cell death of MV4-11 cells compared to inhibition of FLT3 or Mnk2 alone. [ABSTRACT FROM AUTHOR]

Highlights: [•] Performance of three types of coatings for steel plates against corrosion is evaluated. [•] Three experimental techniques related to chloride-induced corrosion were used in the study. [•] The results show that epoxy coating performed the best against chloride-induced corrosion. [Copyright &y& Elsevier]

CDK8 regulates transcription either by phosphorylation of transcription factors or, as part of a four-subunit kinase module, through a reversible association of the kinase module with the Mediator complex, a highly conserved transcriptional coactivator. Deregulation of CDK8 has been found in various types of human cancer, while the role of CDK8 in supressing anti-cancer response of natural killer cells is being understood. Currently, CDK8-targeting cancer drugs are highly sought-after. Herein we detail the discovery of a series of novel pyridine-derived CDK8 inhibitors. Medicinal chemistry optimisation gave rise to 38 (AU1-100), a potent CDK8 inhibitor with oral bioavailability. The compound inhibited the proliferation of MV4-11 acute myeloid leukaemia cells with the kinase activity of cellular CDK8 dampened. No systemic toxicology was observed in the mice treated with 38. These results warrant further pre-clinical studies of 38 as an anti-cancer agent. Image 1 • Novel 3,4,5-trisubstituted pyridines were discovered as potent CDK8 inhibitors. • 38 selectively inhibited proliferation of MV4-11 over 18 human cancer cell lines. • 38 was orally bioavailable in rats and mice. • Administration of 38 did not induce systemic toxicity in mice. [ABSTRACT FROM AUTHOR]