Developing Supramolecular Metallogel Derived from Pd2L4 Cage Molecule for Delivering an Anti-Cancer Drug to Melanoma Cell B16-F10.

Supramolecular gels are an important class of materials that are promising for its wide range of applications including drug delivery. While supramolecular gels are intrinsically porous because of the 3D nano-matrix (gel matrix) that is being formed due to supramolecular self-assembly process involving the gelator molecules during gelation, additional nanopores can be introduced to the overall gel if the gelator molecule itself holds molecular cavity such as metal-organic-cage (MOC) molecules. A MOC having the molecular formula [(Pd2L24).4NO3].3H2O.2DMF.MeOH (Pd-cage) (L2=5-Azido-N,N'-di-pyridin-3-yl-isophthalamide) was successfully synthesized and characterized by FT-IR, 1H NMR, ESI-MS and single crystal X-ray diffraction. Stimuli-reversible supramolecular metallogel PdG could easily be formed from Pd-cage in DMSO/water mixture. The molecular cage of Pd-cage was demonstrated to be available for loading an anti-cancer drug namely doxorubicin (DOX). Subsequently, DOX was also loaded within PdG and delivered to melanoma cell line B16-F10 displaying significant anti-cancer activity as revealed by both MTT and scratch assay. Rheoreversibility of PdG and its ability to load and deliver DOX to cancer cells clearly raised hope for developing this metallogel further as topical anticancer gel.

ExoDS: a versatile exosome-based drug delivery platform to target cancer cells and cancer stem cells.

Chemotherapy drugs like doxorubicin (Dox) are widely used in middle-income countries around the world to treat various types of cancers, including breast cancer. Although they are toxic, they are still widely used to treat cancer. Delivering chemotherapy drugs directly to cancer cells to reduce side effects remains a challenge. Moreover, modern research gave rise to cancer stem cell theory, which implicated cancer stem cells in tumor initiation, progression, and relapse. This makes it imperative to target cancer stem cells to achieve complete remission. Our work highlights the development of an exosome-based targeted drug delivery vehicle. These exosomes were isolated from mature dendritic cells (mDCs) and encapsulated with doxorubicin (ExoDS). Our results showed that ExoDS specifically targeted breast cancer cells and breast cancer stem cells. Further analysis revealed that ExoDS did not induce any significant apoptosis in healthy mammary cells and peripheral blood mononuclear cells (PBMCs) isolated from healthy individuals and breast cancer patients. ExoDS was also found to target circulating tumor cells (CTCs) isolated from patient blood. ExoDS also showed equal efficiency compared to free doxorubicin in vivo. We also observed that ExoDS reduced the expression of cancer stem cell markers in murine tumor tissues. Altogether, this work provides novel insights into how mDC-derived exosomes can be used to specifically target cancer cells and cancer stem cells.

Network Modeling and Control of Dynamic Disease Pathways, Review and Perspectives.

Dynamic disease pathways are a combination of complex dynamical processes among bio-molecules in a cell that leads to diseases. Network modeling of disease pathways considers disease-related bio-molecules (e.g. DNA, RNA, transcription factors, enzymes, proteins, and metabolites) and their interaction (e.g. DNA methylation, histone modification, alternative splicing, and protein modification) to study disease progression and predict therapeutic responses. These bio-molecules and their interactions are the basic elements in the study of the misregulation in the disease-related gene expression that lead to abnormal cellular responses. Gene regulatory networks, cell signaling networks, and metabolic networks are the three major types of intracellular networks for the study of the cellular responses elicited from extracellular signals. The disease-related cellular responses can be prevented or regulated by designing control strategies to manipulate these extracellular or other intracellular signals. The paper reviews the regulatory mechanisms, the dynamic models, and the control strategies for each intracellular network. The applications, limitations and the prospective for modeling and control are also discussed.

Gorlin-Goltz Syndrome - A Rare Case Entity in Young Child.

Gorlin-Goltz syndrome (GGS) is an infrequent multisystemic disease with an autosomal dominant trait, which depicted presence of numerous basal cell carcinoma in conjunction with multiorgan abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the keratocystic odontogenic tumour are usually one of the first manifestations of the syndrome. This article includes a case report of the GGS with regard to its history, incidence, etiology, features, investigations, diagnostic criteria, keratocystic odontogenic tumour and treatment modalities.

Understanding the Application of Mechanical Dyssynchrony in Patients with Heart Failure Considered for CRT.

Over the past two decades of CRT use, the failure rate has remained around 30-35%, despite several updates in the guidelines based on the understanding from multiple trials. This review article summarizes the role of mechanical dyssynchrony in the selection of heart failure patients for cardiac resynchronization therapy. Understanding the application of mechanical dyssynchrony has also evolved during these past two decades. There is no role of lone mechanical dyssynchrony in the patient selection for CRT. However, mechanical dyssynchrony can complement the electrocardiogram and clinical criteria and improve patient selection by reducing the failure rate. An oversimplified approach to mechanical dyssynchrony assessment, such as just estimating time-to-peak delays between segments, should not be used. Instead, methods that can identify the underlying pathophysiology of HF and are representative of a substrate to CRT should be applied.

A Rare Case of Central Odontogenic Fibroma of the Mandible.

The benign tumor central odontogenic fibroma (COF) accounts for less than 1% of all the existing odontogenic tumors. The mandibular or maxillary cortical plate is seen to show asymptotic diversification. It has been characterized as a benign jaw neoplasm. Radiographically, it primarily manifests as a multilocular radiolucency. Histologically, it comprises fibroblasts and mature collagen fibers. The popular choice for the management of COFs is enucleation, followed by the extraction of associated teeth. COFs have maintained a track record of showing rare chances of recurrence following surgery. COF was detected in a 38-year-old female who had edema in the lower right front tooth region. The lesion was surgically removed, and a histopathological examination was performed. Many case reports of COF have been stated in the literature. This indicates that cases of COF are not a rare appearance.