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Jianxin Zhang,1 Chen Ming,2 Wenzhi Zhang,3 Patrick Nwabueze Okechukwu,4 Beata Morak-Młodawska,5 Krystian Pluta,5 Małgorzata Jeleń,5 Abdah Md Akim,6 Kok-Pian Ang,3 Kah Kooi Ooi6,71Department of Gynecology and Obstetrics, Capital Medical University Affiliated Beijing Chaoyang Hospital, Beijing, 2Department of Gynecologic Oncology, Taizhou People’s Hospital, Jiangsu, People’s Republic of China; 3Innoresearch, Subang Jaya, 4Department of Biotechnology, Faculty of Applied Sciences, UCSI University, Kuala Lumpur, Malaysia; 5Department of Organic Chemistry, School of Pharmacy with the Division of Laboratory Medicine, The Medical University of Silesia, Sosnowiec, Poland; 6Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, 7Research Centre for Crystaline Materials, School of Science and Technology, Sunway University, Petaling Jaya, MalaysiaAbstract: The asymptomatic properties and high treatment resistance of ovarian cancer result in poor treatment outcomes and high mortality rates. Although the fundamental chemotherapy provides promising anticancer activities, it is associated with severe side effects. The derivative of phenothiazine, namely, 10H-3,6-diazaphenothiazine (PTZ), was synthesized and reported with ideal anticancer effects in a previous paper. In this study, detailed anticancer properties of PTZ was examined on A2780 ovarian cancer cells by investigating the cytotoxicity profiles, mechanism of apoptosis, and cell invasion. Research outcomes revealed PTZ-induced dose-dependent inhibition on A2780 cancer cells (IC50 =0.62 µM), with significant less cytotoxicity toward HEK293 normal kidney cells and H9C2 normal heart cells. Generation of reactive oxygen species (ROS) and polarization of mitochondrial membrane potential (Δψm) suggests PTZ-induced cell death through oxidative damage. The RT2 Profiler PCR Array on apoptosis pathway demonstrated PTZ-induced apoptosis via intrinsic (mitochondria-dependent) and extrinsic (cell death receptor-dependent) pathway. Inhibition of NF-κB and subsequent inhibition of (BIRC6-XIAP) complex activities reduced the invasion rate of A2780 cancer cells penetrating through the Matrigel™ Invasion Chamber. Lastly, the cell cycle analysis hypothesizes that the compound is cytostatic and significantly arrests cell proliferation at G2/M phase. Hence, the exploration of the underlying anticancer mechanism of PTZ suggested its usage as promising chemotherapeutic agent.Keywords: anticancer, programmed cell death, ovarian cancer, oxidative damage, mitochondrial function disruption, cancer cell invasion

Transdermal patches are a non-invasive method of drug administration. It is an adhesive patch designed to deliver a specific dose of medication through the skin and into the bloodstream throughout the body. Transdermal drug delivery has several advantages over other routes of administration, for instance, it is less invasive, patient-friendly, and has the ability to bypass first-pass metabolism and the destructive acidic environment of the stomach that occurs upon the oral ingestion of drugs. For decades, transdermal patches have attracted attention and were used to deliver drugs such as nicotine, fentanyl, nitroglycerin, and clonidine to treat various diseases or conditions. Recently, this method is also being explored as a means of delivering biologics in various applications. Here, we review the existing literatures on the design and usage of medical patches in transdermal drug delivery, with a focus on the recent advances in innovation and technology that led to the emergence of smart, dissolvable/biodegradable, and high-loading/release, as well as 3D-printed patches.

The year 2021 marks the 100th anniversary of the momentous discovery of insulin. Through years of research and discovery, insulin has evolved from poorly defined crude extracts of animal pancreas to recombinant human insulin and analogues that can be prescribed and administered with high accuracy and efficacy. However, there are still many challenges ahead in clinical settings, particularly with respect to maintaining optimal glycemic control whilst minimizing the treatment-related side effects of hypoglycemia and weight gain. In this review, the chronology of the development of rapid-acting, short-acting, intermediate-acting, and long-acting insulin analogues, as well as mixtures and concentrated formulations that offer the potential to meet this challenge, are summarized. In addition, we also summarize the latest advancements in insulin delivery methods, along with advancement to clinical trials. This review provides insights on the development of insulin treatment for diabetes mellitus that may be useful for clinicians in meeting the needs of their individual patients. However, it is important to note that as of now, none of the new technologies mentioned have superseded the existing method of subcutaneous administration of insulin.

Osteoblasts play an important role in bone regeneration and repair. The hypoxia condition in bone occurs when bone undergoes fracture, and this will trigger a series of biochemical and mechanical changes to enable bone repair. Hence, it is interesting to observe the metabolites and metabolism changes when osteoblasts are exposed to hypoxic condition. This study has looked into the response of human osteoblast hFOB 1.19 under normoxic and hypoxic conditions by observing the cell growth and utilization of metabolites via Phenotype MicroArrays™ under these two different oxygen concentrations. The cell growth of hFOB 1.19 under hypoxic condition showed better growth compared to hFOB 1.19 under normal condition. In this study, osteoblast used glycolysis as the main pathway to produce energy as hFOB 1.19 in both hypoxic and normoxic conditions showed cell growth in well containing dextrin, glycogen, maltotriose, D-maltose, D-glucose-6-phospate, D-glucose, D-mannose, D-Turanose, D-fructose-6-phosphate, D-galactose, uridine, adenosine, inosine and α-keto-glutaric acid. In hypoxia, the cells have utilized additional metabolites such as α-D-glucose-1-phosphate and D-fructose, indicating possible activation of glycogen synthesis and glycogenolysis to metabolize α-D-glucose-1-phosphate. Meanwhile, during normoxia, D-L-α-glycerol phosphate was used, and this implies that the osteoblast may use glycerol-3-phosphate shuttle and oxidative phosphorylation to metabolize glycerol-3-phosphate.

The asymptomatic properties and high treatment resistance of ovarian cancer result in poor treatment outcomes and high mortality rates. Although the fundamental chemotherapy provides promising anticancer activities, it is associated with severe side effects. The derivative of phenothiazine, namely, 10 H -3,6-diazaphenothiazine (PTZ), was synthesized and reported with ideal anticancer effects in a previous paper. In this study, detailed anticancer properties of PTZ was examined on A2780 ovarian cancer cells by investigating the cytotoxicity profiles, mechanism of apoptosis, and cell invasion. Research outcomes revealed PTZ-induced dose-dependent inhibition on A2780 cancer cells (IC 50 =0.62 µM), with significant less cytotoxicity toward HEK293 normal kidney cells and H9C2 normal heart cells. Generation of reactive oxygen species (ROS) and polarization of mitochondrial membrane potential (ΔΨm) suggests PTZ-induced cell death through oxidative damage. The RT 2 Profiler PCR Array on apoptosis pathway demonstrated PTZ-induced apoptosis via intrinsic (mitochondria-dependent) and extrinsic (cell death receptor-dependent) pathway. Inhibition of NF-κB and subsequent inhibition of (BIRC6-XIAP) complex activities reduced the invasion rate of A2780 cancer cells penetrating through the Matrigel™ Invasion Chamber. Lastly, the cell cycle analysis hypothesizes that the compound is cytostatic and significantly arrests cell proliferation at G 2 /M phase. Hence, the exploration of the underlying anticancer mechanism of PTZ suggested its usage as promising chemotherapeutic agent., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Interactions between parasite, host and host-associated microbiota are increasingly understood as important determinants of disease progression and morbidity. Salmon lice, including the parasitic copepod Lepeophtheirus salmonis and related species, are perhaps the most important problem facing Atlantic Salmon aquaculture after feed sustainability. Salmon lice parasitize the surface of the fish, feeding off mucus, scales and underlying tissue. Secondary bacterial infections are a major source of associated morbidity. In this study we tracked the diversity and composition of Salmo salar skin surface microbiota throughout a complete L. salmonis infection cycle among 800 post-smolts as compared to healthy controls. Among infected fish we observed a significant reduction in microbial richness (Chao1, P = 0.0136), raised diversity (Shannon, P < 7.86e-06) as well as highly significant destabilisation of microbial community composition (Pairwise Unifrac, beta-diversity, P < 1.86e-05; P = 0.0132) by comparison to controls. While undetectable on an individual level, network analysis of microbial taxa on infected fish revealed the association of multiple pathogenic genera (Vibrio, Flavobacterium, Tenacibaculum, Pseudomonas) with high louse burdens. We discuss our findings in the context of ecological theory and colonisation resistance, in addition to the role microbiota in driving primary and secondary pathology in the host.

Comparative genome scans can be used to identify chromosome regions, but not traits, that are putatively under selection. Identification of targeted traits may be more likely in recently domesticated populations under strong artificial selection for increased production. We used a North American Atlantic salmon 6K SNP dataset to locate genome regions of an aquaculture strain (Saint John River) that were highly diverged from that of its putative wild founder population (Tobique River). First, admixed individuals with partial European ancestry were detected using STRUCTURE and removed from the dataset. Outlier loci were then identified as those showing extreme differentiation between the aquaculture population and the founder population. All Arlequin methods identified an overlapping subset of 17 outlier loci, three of which were also identified by BayeScan. Many outlier loci were near candidate genes and some were near published quantitative trait loci (QTLs) for growth, appetite, maturity, or disease resistance. Parallel comparisons using a wild, nonfounder population (Stewiacke River) yielded only one overlapping outlier locus as well as a known maturity QTL. We conclude that genome scans comparing a recently domesticated strain with its wild founder population can facilitate identification of candidate genes for traits known to have been under strong artificial selection.

Endothelial dysfunction has been implicated in the pathogenesis of atherosclerosis. Salvia miltiorrhiza (danshen) is a traditional Chinese medicine that has been effectively used to treat cardiovascular disease. Cryptotanshinone (CTS), a major lipophilic compound isolated from S. miltiorrhiza, has been reported to possess cardioprotective effects. However, the anti-atherogenic effects of CTS, particularly on tumor necrosis factor-α (TNF-α)-induced endothelial cell activation, are still unclear. This study aimed to determine the effect of CTS on TNF-α-induced increased endothelial permeability, monocyte adhesion, soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), monocyte chemoattractant protein 1 (MCP-1) and impaired nitric oxide production in human umbilical vein endothelial cells (HUVECs), all of which are early events occurring in atherogenesis. We showed that CTS significantly suppressed TNF-α-induced increased endothelial permeability, monocyte adhesion, sICAM-1, sVCAM-1 and MCP-1, and restored nitric oxide production. These observations suggest that CTS possesses anti-inflammatory properties and could be a promising treatment for the prevention of cytokine-induced early atherogenesis.

Ambient air particulates were collected using high volume samplers at seven locations throughout Singapore. The particulates were analyzed for eleven polynuclear aromatic hydrocarbons (PAH) using high performance liquid chromatography (HPLC) with fluorescence detection. Several sample preparation techniques were used to determine which method would yield the most PAHs from the bulk sample matrix. PAH profiles (standardised against the concentration of benzo(a)pyrene) were obtained to characterise the different sampling sites chosen.