Advancement of targeted protein degradation strategies as therapeutics for undruggable disease targets.

Targeted protein degradation (TPD) aids in developing novel bifunctional small-molecule degraders and eliminates proteins of interest. The TPD approach shows promising results in oncological, neurogenerative, cardiovascular and gynecological drug development. We provide an overview of technology advancements in TPD, including molecular glues, proteolysis-targeting chimeras (PROTACs), lysosome-targeting chimeras, antibody-based PROTAC, GlueBody PROTAC, autophagy-targeting chimera, autophagosome-tethering compound, autophagy-targeting chimera and chaperone-mediated autophagy-based degraders. Here we discuss the development and evolution of the TPD field, the variety of proteins that PROTACs target and the biological repercussions of their degradation. We particularly highlight the recent improvements in TPD research that utilize autophagy or the endolysosomal pathway, which enables the targeting of undruggable targets.

Functionalized Sulfur-Containing Heterocyclic Analogs Induce Sub-G1 Arrest and Apoptotic Cell Death of Laryngeal Carcinoma In Vitro.

In this study, we speculate that the hydroxyl-containing benzo[b]thiophene analogs, 1-(3-hydroxybenzo[b]thiophen-2-yl) ethanone (BP) and 1-(3-hydroxybenzo[b]thiophen-2-yl) propan-1-one hydrate (EP), might possess antiproliferative activity against cancer cells. Hydroxyl-containing BP and EP show selectivity towards laryngeal cancer cells (HEp2), with IC50 values of 27.02 ± 1.23 and 35.26 ± 2.15 µM, respectively. The hydroxyl group present in the third position is responsible for the anticancer activity and is completely abrogated when the hydroxyl group is masked. BP and EP enhance the antioxidant enzyme activity and reduce the ROS production, which are correlated with the antiproliferative effect in HEp-2 cells. An increase in the BAX/BCL-2 ratio occurs during the BP and EP treatment and activates the caspase cascade, resulting in apoptosis stimulation. It also arrests the cells in the Sub-G1 phase, indicating the induction of apoptosis. The molecular docking and simulation studies predicted a strong interaction between BP and the CYP1A2 protein, which could aid in combinational therapy by enhancing the bioavailability of the drugs. BP and EP possess an antioxidant property with low antiproliferative effects (~5.18 µg/mL and ~7.8 µg/mL) as a standalone drug, therefore, they can be combined with other drugs for effective chemotherapy that might trigger the effect of pro-oxidant drug on healthy cells.

Biosorptive ascendency of plant based biosorbents in removing hexavalent chromium from aqueous solutions - Insights into isotherm and kinetic studies.

Chromium is a toxic heavy metal prevalent in higher levels in aqueous matrices owing to industrial applications. Whilst being a key player in industries, the environmental issues caused by Cr(VI) are highly deleterious. Adsorptive remediation is found to be an effective method adopted by researchers in the past decades for Cr(VI) removal from water streams in which variety of naturally available biosorbents have been explored for handling Cr(VI). This review article briefly sketches up the biosorptive potential of plant-based biosorbents used in raw and chemically modified form for the optimum exclusion of Cr(VI) from aqueous sources. Mechanisms and kinetic behavior of the removal process are also discussed. pH of the solution and initial Cr(VI) concentration were found to be the key parameters in Cr removal. The mechanism of Cr removal from aqueous systems was elucidated to be either adsorption or adsorption-coupled-reduction. After precise discussion on various plant-based biosorbents with their maximum adsorption capacities, desorption and regeneration potential, it is perceived that plant-based biosorbents are superior options for Cr(VI) elimination from aqueous streams.

Nanomaterials: Synthesis and Applications in Theranostics.

Nanomaterials are endowed with unique features and essential properties suitable for employing in the field of nanomedicine. The nanomaterials can be classified as 0D, 1D, 2D, and 3D based on their dimensions. The nanomaterials can be malleable and ductile and they can be drawn into wires and sheets. Examples of nanomaterials are quantum dots (0D), nanorods, nanowires (1D), nanosheets (2D), and nanocubes (3D). These nanomaterials can be synthesized using top-down and bottom-up approaches. The achievements of 0D and 1D nanomaterials are used to detect trace heavy metal (e.g., Pb2+) and have higher sensitivity with the order of five as compared to conventional sensors. The achievements of 2D and 3D nanomaterials are used as diagnostic and therapeutic agents with multifunctional ability in imaging systems such as PET, SPECT, etc. These imaging modalities can be used to track the drug in living tissues. This review comprises the state-of-the-art of the different dimensions of the nanomaterials employed in theranostics. The nanomaterials with different dimensions have unique physicochemical properties that can be utilized for therapy and diagnosis. The multifunctional ability of the nanomaterials can have a distinct advantage that is used in the field of theranostics. Different dimensions of the nanomaterials would have more scope in the field of nanomedicine.

Simple isolation and characterization of seminal plasma extracellular vesicle and its total RNA in an academic lab.

Extracellular vesicles (EVs) are small membrane-bound sacs, identified in many body fluids of humans. Standard extracellular vesicle separation methods such as differential and ultracentrifugation are very expensive, not affordable in academic labs. So, the current research tried to isolate seminal plasma EVs using polyethylene glycol (PEG) precipitation process. Normospermia semen from "Milann - The Fertility Center" processed to isolate EVs by PEG method. Nanodrop spectrophotometer showed presence of EVs by indirectly measuring protein content of precipitated EVs. EVs isolated by PEG precipitation showed a wide size range from 30 to 1000 nm with Z average of 75.4 nm and a PI of 0.464, whereas ultracentrifuge sample showed size range of 60-1000 nm with Z average of 501.3 nm with a PI of 0.692. Edax analysis also showed good elemental pattern. Total RNA extraction from PEG EVs analysed with nanodrop spectrophotometer, showed presence of RNA content in varying concentrations obtained from different ratios in nanograms. Thus, the current study concludes that seminal plasma EVs isolated by PEG precipitation is simple, reproducible and non-sensitive to carry out at academic labs.