Innovative materials against tumour to decrease remarkably the number of persons died by cancer are desired eagerly. To innovate in the medical technologies, tumour accumulative sugar dendritic Gd-DTPA complex MRI contrast agent (DEN-OH) and IER5/Cdc25B targeted novel phospha sugar antitumour agents (TBMPP) were prepared and evaluated preclinically. These novel medicinal materials were revealed to exert excellent characteristics against tumour cells. DEN-OH was prepared by introduction of protected sugar dendritic parts to the ligand of diethylenetriamine pentaacetic acid (DTPA) and the successive complex formation with Gd (III) and hydrolysis. The prepared DEN-OH for MRI contrast agent with the less concentration (10% Gd concentration of Gd-DTPA complex) showed quite clearer images of quite early stage cancer. Phospha sugar derivatives were prepared by new synthetic pathway to construct the compound library. Deoxybromophospha sugar derivatives such as TBMPP (Tribromophospha sugar derivative) prepared from phospholene derivative were first found to exert quite strong and wide spectral antitumor activities by in vitro evaluation against various kinds of leukemia cells such as K562, U937, etc. cell lines as well as solid cancer cells. Mechanistic studies with TBMPP against leukemia cells by Western blotting showed that the phospha sugar enhanced the expression of IER5, suppressed the expression of Cdc25B against tumour cells selectively and specifically, and then induced apoptosis at the mitosis step of the tumour cell cycle. Invivo evaluation for TBMPP was successfully performed by using a nude mouse transplanted by K562 cells on the skin.

For a long time the idea of separated diagnostic and therapeutic approaches was predominant in the development of new drugs in medicine. However, recently a significant increase has been observed in the trend to create drugs which effectively combine diagnostic and therapeutic approaches. Such the drugs termed the agents of theranostics allow to determine the tumor localization in the body and to provide a therapeutic effect on it. Furthermore, in some cases theranostic agent allows to provide the real time monitoring of individual therapeutic response to the treatment procedure. Recently we reported on the preparation and studies of the photophysical properties of new fluorescent porphyrazine pigments which have been found to be an excellent platform for drugs with the unique combination of various biomedical functions: Bimodal (fluorescent/ MRI) diagnostic agents, sensitive optical sensors of intracellular viscosity and highly efficient photosensitizers in photodynamic therapy. Here we report the new series of aryl-cyano porphyrazine pigments containing n-donor oxygen atoms in the aromatic groups of peripheral frame of tetrapyrrol macrocycle. They demonstrate significantly improved photocytoxic properties and the potential for biomedical application as photosensitizers in PDT in comparison with previously reported aryl-cyano porphyrazine Pz1. Moreover, this series of tetrapyrrols the structural feature of which is the alternation of strongly electron withdrawing CN and Pi-donor aryl groups in the peripheral frame of macrocycle have been found to be novel fluorescent molecular rotor type dyes with the desirable feature of intense absorption and emission of red light that can be useful in vivo to enable deep tissue penetration in the tissue optical window. High efficacy of all the series as the fluorescent sensors of local viscosity in a wide viscosity range, had been demonstrated. Furthermore, we first proposed semi-empirical model describing photophysical behavior of novel porphyrazine series. The model was verified with fluorescence decay investigations for all the porphyrazine series, T.

Marine benthic invertebretes (Sponges and soft corals etc.) are widely distributed in the coral reefs of the world oceans. Of them, the animals belonging to the genus Sarcophyton (phylum Cnidaria, class Anthozoa, subclass Octocorallia, order Alcyonaceae, family Alcyoniidae) are very prolific and are the intense research subjects for marine natural product chemists. Literature checking revealed that Sarcophyton animals can produce different structural classes of secondary metabolites exhibiting various interesting biological activities ranging from antifouling, anti-inflammatory to cytotoxic activities. Among the metabolites reported, cembrane-type diterpenes are the most frequently encountered. Moreover, biscembranoids, characterized by the complex and highly oxygeneted macrocyclic frameworks, which are formally synthesized from two different cembranoid units via a probable [4+2] Diels-Alder cyclic addition, are unique and typical natural products from soft corals of the genera Sarcophyton. Due to the flexible nature of the macrocycles accompanying with the highly diverse substitution patterns, it has been being a challenging task for their structural, in particular, the absolute stereochemistry, determination by natural product chemists. In this presentation, I’ll present the latest chemical studies and promising bioactivity results on the sarcophyton corals and sponge spongia officinalis collected from South China Sea. All work has been performed in close collaboration with marine biologists and with pharmacologists.

Host-guest inclusion of two drugs, phenylephrine hydrochloride and synephrine with α and β-cyclodextrins and their applications in biological Sciences have been investigated by physicochemical and microbiological approach. Phenylephrine hydrochloride (PEH) is a selective α1-adrenergic receptor agonist of the phenethylamine class used primarily in cold and flu conditions as an antipyretic, analgesic drug to relief pain. Alkaloid synephrine (SNP) was first extracted as a natural product from the leaves of various citrus trees is used as bronchial muscle reluctant, increases blood pressure in the patients suffering from low blood pressure. Formation of Host Guest Inclusion complexes of PEH and SNP with the CDs have increased the activities of the drugs concerned and controlled the dose for regulatory dischargement i.e. the drugs can be released as per requirement of the patient to avoid the side effects which have been explored in this research paper.

Healthcare access is a worldwide challenge. Everyday, patients from all over the world are denied access to elsewhere approved health innovations for arbitrary reasons. I have also been there myself. I experienced personal hardships friends who passed away before ever accessing the medicines they needed. I was determined to find a way to undo the injustices of medicines access on a global scale and to accelerate this process to patients all over the world. The creation of TheSocialMedwork is a timely and critical one, with only 11 years separating us from the 2030 health targets of the United Nations. It is our responsibility and duty to eradicate this challenge as soon as possible. Our aim is to keep pushing for a change in the access to healthcare landscape every single day. We have now safely delivered over 5,500 latest innovative medicines to over 75 countries, years before the official availability in these countries. Under the named patient import basis, TheSocialMedwork is safely and legally delivering medicines to all over the world. TheSocialMedwork’s end goal is global health access for everyone regardless of their financial situation. This is why we are working towards crowd funding, blockchain transparency, pricing algorithms and conditional reimbursement pilots. In the future we aim to further work together with pharma companies, patient organizations and healthcare professionals to provide patients with the latest and most innovative treatments at their fingertips the second they become approved around the world. Let’s make this world work for everyone!

For many, the promises of digital pathology (DP) to streamline workflows, improve laboratory quality and to improve patient care are not readily apparent, especially when faced with the high costs of deploying DP. Calculating return on investment from introducing yet another layer of complexity and handoffs in an already complicated surgical pathology process can be riddled with inaccuracies and assumptions, such as major laboratory personnel (FTE) savings, decreases in turn-around time, and increased potential business through digital consults. Recently, the application of machine learning and artificial intelligence (AI) to whole slides images has emerged as a primary use case for the adoption of large-scale digital pathology efforts. With AI, multiple use cases now exists, that have the potential to transform the way pathology is practiced, both within the anatomic pathology laboratory and the pathologist sign out workspaces. This talk will describe how, by understanding the fundamental requirements, barriers to adoption, and opportunities for future growth related to digital pathology, one will be able to successfully determine how to deploy this new technology to its greatest ability.

The application of convolutional neural network (CNN) based analysis to histopathological subject matter has already demonstrated significant utility for both general image classification tasks, as well as for implementation of unsupervised partitioning of datasets into multiple appropriate diagnostic subclasses. This approach is generally successful in settings where sufficient case numbers are available. Use of CNNs is attractive in that it can help to avoid the need for laborious generation of ground truth maps, as performed by subject matter experts. However, CNNs are limited in that their convergence on a generalizable solution often requires the availability of 100’s, if not 1000’s, of training set images. This lowers the utility of this approach for certain classes of histopathological subject matter, where large cohorts of cases and images are unavailable. To address this limitation, we present the use of an additional preprocessing stage, with the use of hand-crafted feature classifiers, prior to the application of conventional CNN-based methodologies. This multi-stage approach has been applied to a number of histology classification use-cases, with preliminary results demonstrating that in many cases, the requirement for having hundreds or thousands of images can be significantly reduced, to instead only requiring a few representational images. A number of use cases will be presented, demonstrating consistently high ROC performance, even in the setting of having small numbers of initial cohort images in the training set.

The last thirty years have registered a progressive and dramatic increase in the incidence of obesity and type 2 diabetes mellitus world-wide. Metabolic Syndrome, one of the most commonly conditions associated with obesity and insulin resistance, has also increased considerably. The latest releases from the WHO estimate that approximately 1 billion people worldwide are obese, and more than 500 million are diabetic or pre- diabetic. Interestingly, increasing evidence suggest that our current western diet is hypercaloric but hyponutritive, as it is lacking essential micronutrients and minerals. Our laboratory has focused on the possible role of reduced cellular magnesium levels in the dysregulation of cellular and systemic glucose homeostasis. Experimental data obtained in animal and cellular models, including cells of human origin support the conclusion that cellular magnesium regulates transmembrane glucose transport as well as its utilization, and neosynthesis in gluconeogenic tissues, by modulating the activity of specific cellular enzymes and insulin-mediated signaling. Regardless of the tissue considered, decreased cellular and serum magnesium levels impact the proper operation of Glut 4, and Glut 2 transporters, thus limiting the ability of tissues like heart, muscles, liver, and possibly beta-islets, to effectively transport glucose into the cell to support glycolysis, ATP production, and ultimately storage as glycogen. As a consequence, gluconeo-genesis becomes erroneously activated, further enhancing the circulating levels of glucose and resulting in the dysregulation of fatty acids, cholesterol, and protein degradation, to support gluconeogenic activity through increased cortisol production and insulin resistance. Also, decreased cellular magnesium levels appear to contribute directly to increased basal inflammation within tissues, further impairing insulin responsiveness and systemic metabolic homeostasis. Altogether, our results argue for the necessity to better understand the role that micronutrients play in modulating both organ- specific and systemic metabolism and inflammation, to ultimately identifying more effective therapeutic and dietary approaches.

In recent years, convolutional neural networks (CNN) have revolutionized the field of computer aided digital image analysis due to their accuracy in classifying and recognizing objects /patterns from different subject matters, including histopathological images. Aside from object classification, CNN is also useful for object detection/tracking and semantic segmentation. There is a lot of potential for deep learning to change and improve the practice of pathology due to the highly visual nature of the field, especially in tasks that pathologists find boring and tedious such as finding mitosis and counting cells. Other example applications of CNN in pathology include classification of lesions (e.g. benign vs. malignant), cancer localization, nuclei identification, and segmentation of regions of interests in an image. In the image below, a CNN model based on U-Net, together with a ground truth map, was able to accurately highlight regions of glomeruli in a kidney section. Running CNN experiments used to require a significant amount of programming expertise. Fortunately, open-source tools that need minimal or no programming knowledge such as Tensorflow and Orange (Biolab) are now available, making deep learning accessible to a wider audience, including pathologists.