Recent developments in photodynamic therapy and its application against multidrug resistant cancers.

Recently, photodynamic therapy (PDT) has received a lot of attention for its potential use in cancer treatment. It enables the therapy of a multifocal disease with the least amount of tissue damage. The most widely used prodrug is 5-aminolevulinic acid, which undergoes heme pathway conversion to protoporphyrin IX, which acts as a photosensitizer (PS). Additionally, hematoporphyrin, bacteriochlorin, and phthalocyanine are also studied for their therapeutic potential in cancer. Unfortunately, not every patient who receives PDT experiences a full recovery. Resistance to different anticancer treatments is commonly observed. A few of the resistance mechanisms by which cancer cells escape therapeutics are genetic factors, drug-drug interactions, impaired DNA repair pathways, mutations related to inhibition of apoptosis, epigenetic pathways, etc. Recently, much research has been conducted to develop a new generation of PS based on nanomaterials that could be used to overcome cancer cells' multidrug resistance (MDR). Various metal-based, polymeric, lipidic nanoparticles (NPs), dendrimers, etc, have been utilized in the PDT application against cancer. This article discusses the detailed mechanism by which cancer cells evolve towards MDR as well as recent advances in PDT-based NPs for use against multidrug-resistant cancers.

Advances in modified antimicrobial peptides as marine antifouling material.

Biofouling is the undesirable attachment of organisms and their by-products on surfaces. It has become a severe problem in the industries that utilize devices and facilities in the marine environment. Several antifouling strategies have been developed, but many have adverse effects on numerous species, the surrounding environment, and marine devices. However, antimicrobial peptides (AMPs) have emerged as a promising non-toxic biomaterial that can modify the submerged surfaces to inhibit biofouling. AMPs are getting recognized as a highly potent material as they exhibit strong antimicrobial activity against fouling organisms and resistance towards biofilm formation. This review discusses the latest developments made in recent years regarding applying AMPs as prominent marine antifouling material. The various properties of AMPs, including structural, functional characteristics, and mechanism of action, are presented. Different types of modification of AMPs to improve their stability, efficacy, and activity against fouling organisms are discussed in detail. Furthermore, future perspectives and significant improvements required to make AMPs an integrative part of the marine antifouling process are reviewed.

Exosomal long noncoding RNAs - the lead thespian behind the regulation, cause and cure of autophagy-related diseases.

Recent advances in exosome biology have revealed significant roles of exosome and their contents in intercellular communication. Among various exosomal content, long non-coding RNAs (lncRNAs), which have a large size (˃ 200 nt) and lack protein coding potential, are known to play key roles in intercellular communication and novel biomarkers of various metabolic disorders. Moreover, long non-coding RNAs are often involved in the regulation of various cellular processes such as autophagy, apoptosis, cell proliferation. On the other hand, autophagy is the central regulating point that controls the various metabolic functions of the body. This process is known to prevent diseases and promote longevity. Therefore, the present review discusses the relationship between diseases and autophagy, and also look into the biological functions of exosome-associated lncRNAs in regulating autophagy. Furthermore, this review will summarize some of the studies that provide novel insights into the pathogenesis of autophagy-related diseases followed by the non-canonical roles played by autophagy and related proteins in the development of exosome biogenesis.

DNA damage induced cellular senescence and it's PTEN-armed exosomes-the warriors against prostate carcinoma cells.

Exosomes are one type of small extracellular vesicles (EVs) having a size range of 30-150 nm and secreted by the endosomal compartment of most eukaryotic cells. It has been found that exosomes (EVs) can serve as a communicating vehicle to transfer information among cells and thus can be associated with numerous physiological and pathological functions. In this study, we have isolated exosomes (EVs) from two different human cancer cell lines. Isolated exosomes (EVs) were characterized by scanning electron microscopy, nanoparticle tracking analysis, DLS, and by western blotting. It was observed that exosomes (EVs) isolated from mock-treated human lung epithelial carcinoma (A549) cells or HeLa cells exerted growth arrest to the human prostate carcinoma (PC3) cells, but no growth arrest was observed in case of normal human lung fibroblast cell line (WI-38). Additionally, exosomes (EVs) isolated from PC3 cells have no effect on PC3 cells. This is also true for exosomes (EVs) isolated from H2O2-induced senescent human lung cancer cells (A549). Analysis of exosome (EVs) content by western blotting reveals the presence of PTEN in the exosome (EVs) of lung cancer cells. Functional analysis of PTEN pathways in PC3 cells indicates the inactivation of Akt in exosome (EV)-treated cells. Therefore, from our study we have concluded that exosomes (EVs) secreted from A549 cells which contain functional PTEN may be used for delivery of PTEN to cancer cells without functional PTEN.

Utilization of Guanidine-Based Ancillary Ligands in Arene-Ruthenium Complexes for Selective Cytotoxicity.

A family of three water-soluble half-sandwich arene-ruthenium complexes, depicted as C 1 -C 3 , having the general formula [Ru(p-cymene)(L)Cl]Cl has been synthesized, where L represents (1H-benzo[d]imidazol-2-yl)guanidine (L 1 ) or (benzo[d]oxazol-2-yl)guanidine (L 2 ) or (benzo[d]thiazol-2-yl)guanidine (L 3 ). The crystal structure of complex C 3 has been determined. The complexes show several absorption bands in the visible and ultraviolet regions, and they also show prominent emission in the visible region while excited near 400 nm. Studies on the interaction of ligands L 1 -L 3 and complexes C 1 -C 3 with calf thymus DNA reveal that the complexes are better DNA binders than the ligands, which is attributable to the imposed planarity of the ruthenium-bound guanidine-based ligand, enabling it to serve as a better intercalator. Molecular docking studies show that the complexes effectively bind with DNA through electrostatic and H-bonding interactions and partial intercalation of the guanidine-based ligands. Cytotoxicity studies carried out on two carcinoma cell lines (PC3 and A549) and on two non-cancer cell lines (BPH1 and WI-38) show a marked improvement in antitumor activity owing to complex formation, which is attributed to improvement in cellular uptake on complex formation. The C 1 complex is found to exhibit the most prominent activity against the PC3 cell line. Inclusion of the guanidine-based ligands in the half-sandwich ruthenium-arene complexes is found to be effective for displaying selective cytotoxicity to cancer cells and also for convenient tracing of the complexes in cells due to their prominent emissive nature.

Stem Cell Aging and Regenerative Medicine.

Stem cells are a promising source for regenerative medicine to cure a plethora of diseases that are currently treated based on either palliative or symptomatic relief or by preventing their onset and progression. Aging-associated degenerative changes in stem cells, stem cell niches, and signaling pathways bring a step by step decline in the regenerative and functional potential of tissues. Clinical studies and experiments on model organisms have pointed out checkpoints that aging will inevitably impose on stem cell aiming for transplantation and hence questions are raised about the age of the donor. In the following discourse, we review the fundamental molecular pathways that are implicated in stem cell aging and the current progress in tissue engineering and transplantation of each type of stem cells in regenerative medicine. We further focus on the consequences of stem cell aging on their clinical uses and the development of novel strategies to bypass those pitfalls and improve tissue replenishment.

The protective role of metformin in autophagic status in peripheral blood mononuclear cells of type 2 diabetic patients.

Autophagy plays an important role in the pathophysiology of type 2 diabetes (T2D). Metformin is the most common antidiabetic drug. The main objective of this study was to explore the molecular mechanism of metformin in starvation-induced autophagy in peripheral blood mononuclear cells (PBMCs) of type 2 diabetic patients. PBMCs were isolated from 10 diabetic patients and 7 non-diabetic healthy volunteers. The autophagic puncta and markers were measured with the help of monodansylcadaverine staining and western blot. Additionally, transmission electron microscopy was also performed. No significant changes were observed in the initial autophagy marker protein levels in PBMCs of T2D after metformin treatment though diabetic PBMCs showed a high level of phospho-mammalian target of rapamycin, p62 and reduced expression of phospho-AMP-activated protein kinase and lysosomal membrane-associated protein 2, indicating a defect in autophagy. Also, induction of autophagy by tunicamycin resulted in apoptosis in diabetic PBMCs as observed by caspase-3 cleavage and reduced expression of Bcl2. Inhibition of autophagy by bafilomycin rendered consistent expression of p62 indicating a defect in the final process of autophagy. Further, electron microscopic studies also confirmed massive vacuole overload and a sign of apoptotic cell death in PBMCs of diabetic patients, whereas metformin treatment reduced the number of autophagic vacuoles perhaps by lysosomal fusion. Thus, our results indicate that defective autophagy in T2D is associated with the fusion process of lysosomes which could be overcome by metformin.

Development of nanotechnology for advancement and application in wound healing: a review.

Wound healing is a series of different dynamic and complex phenomena. Many studies have been carried out based on the type and severity of wounds. However, to recover wounds faster there are no suitable drugs available, which are highly stable, less expensive as well as has no side effects. Nanomaterials have been proven to be the most promising agent for faster wound healing among all the other wound healing materials. This review briefly discusses the recent developments of wound healing by nanotechnology, their applicability and advantages. Nanomaterials have unique physicochemical, optical, and biological properties. Some of them can be directly applied for wound healing or some of them can be incorporated into scaffolds to create hydrogel matrix or nanocomposites, which promote wound healing through their antimicrobial, as well as selective anti- and pro-inflammatory, and proangiogenic properties. Owing to their high surface area to volume ratio, nanomaterials have not only been used for drug delivery vectors but also can affect wound healing by influencing collagen deposition and realignment and provide approaches for skin tissue regeneration.

Is autophagy associated with diabetes mellitus and its complications? A review.

Diabetes mellitus (DM) is an endocrine disorder. In coming decades it will be one of the leading causes of death globally. The key factors in the pathogenesis of diabetes are cellular injuries and disorders of energy metabolism leading to severe diabetic complications. Recent studies have confirmed that autophagy plays a pivotal role in diabetes and its complications. It has been observed that autophagy regulates the normal function of pancreatic ß cells and insulin-target tissues, such as skeletal muscle, liver, and adipose tissue. This review will summarize the regulation of autophagy in diabetes and its complications, and explore how this process would emerge as a potential therapeutic target for diabetes treatment.

Morphology-directing synthesis of rhodamine-based fluorophore microstructures and application toward extra- and intracellular detection of Hg(2+).

A new, easily synthesizable rhodamine-based chemosensor with potential N2O2 donor atoms, L(3), has been characterized by single-crystal X-ray diffraction together with (1)H NMR and high-resolution mass spectrometry (HRMS) studies. L(3) was found to bind selectively and reversibly to the highly toxic Hg(2+) ion. The binding stoichiometry and formation constant of the sensor toward Hg(2+) were determined by various techniques, including UV-vis, fluorescence, and Job's studies, and substantiated by HRMS methods. None of the biologically relevant and toxic heavy metal ions interfered with the detection of Hg(2+) ion. The limit of detection of Hg(2+)calculated by the 3σ method was 1.62 nM. The biocompatibility of L(3) with respect to its good solubility in mixed organic/aqueous media (MeCN/H2O) and cell permeability with no or negligible cytotoxicity provides good opportunities for in vitro/in vivo cell imaging studies. As the probe is poorly soluble in pure water, an attempt was made to frame nano/microstructures in the absence and in the presence of sodium dodecyl sulfate (SDS) as a soft template, which was found to be very useful in synthesizing morphologically interesting L(3) microcrystals. In pure water, micro-organization of L(3) indeed occurred with block-shaped morphology very similar to that in the presence of SDS as a template. However, when we added Hg(2+) to the solution of L(3) under the above two conditions, the morphologies of the microstructures were slightly different; in the first case, a flowerlike structure was observed, and in second case, a simple well-defined spherical microstructure was obtained. Optical microscopy revealed a dotlike microstructure for L(3)-SDS assemblies, which changed to a panicle microstructure in the presence of Hg(2+). UV-vis absorption and steady-state and time-resolved fluorescence studies were also carried out in the absence and presence of Hg(2+), and also the SDS concentration was varied at fixed concentrations of the receptor and guest. The results revealed that the fluorescence intensity increased steadily with [SDS] until it became saturated at ∼7 mM SDS, indicating that the extent of perturbation to the emissive species increases with the increase in [SDS] until it becomes thermodynamically stable. There was also an increase in anisotropy with increasing SDS concentration, which clearly manifests the restriction of movement of the probe in the presence of SDS.

Differential toxicity of rod and spherical zinc oxide nanoparticles on human peripheral blood mononuclear cells.

The cytotoxic and genotoxic potential of rod and spherical zinc oxide nanoparticles (ZnO NPs) were evaluated on human peripheral blood mononuclear cells (PBMCs). Their sizes and shapes were determined by Transmission electron microscopy (TEM) and physical characterizations were done by X-ray diffraction (XRD) and Dynamic light scattering (DLS). The cytotoxic potential of rod ZnO NPs was greater than spherical ZnO NPs when applied to PBMCs and was limited to the proliferative lymphocytes. Rod ZnO NPs produced more reactive oxygen species (ROS) compared to spherical ones. Additionally rod ZnO NPs induced significant DNA damage to PBMCs as revealed by cytokinesis block micronucleus (CBMN) assay and comet assay. On the other hand UV absorption property was enhanced in case of spherical ZnO NPs compared to rod ZnO NPs. Thus, present study implicates the shape dependent differential application of ZnO NPs in our daily life.

Antibacterial activities of polyethylene glycol, tween 80 and sodium dodecyl sulphate coated silver nanoparticles in normal and multi-drug resistant bacteria.

Antibacterial activity of silver nanoparticles coated with different functionalizing agents i.e., polyethylene glycol, tween 80 and sodium dodecyl sulphate were evaluated on both normal and multi-drug resistant strains of bacteria. Under the same reaction conditions, these functionalizing agents were added separately to coat silver nanoparticles. Among these, polyethylene glycol coated nanoparticles were most effective in killing all the bacterial strains which includes Escherichia coli DH5a, Bacillus subtilis, Micrococcus luteus, Staphylococcus aureus and multi-drug resistant clinical isolates of Shigella spp. (flexneri, boydii, sohnea) and Vibrio cholerae. The minimum inhibitory concentration of polyethylene glycol coated silver nanoparticles was also less compared to the other two sets of nanoparticles. Consistence with that polyethylene glycol coated nanoparticles produced more intracellular reactive oxygen species in bacteria. Moreover, when human cell lines MCF7 and Chang Liver were incubated in presence of these nanoparticles for 18 h with same concentrations as used for bacteria, no toxicity was observed. But significant increase in cell killing was observed with longer incubation time. Thus our present investigation implicates the potential therapeutic use of silver nanoparticles as antibacterial agent particularly the polyethylene glycol coated one.

A novel study of antibacterial activity of copper iodide nanoparticle mediated by DNA and membrane damage.

In this article potential activity of nanoparticles (NPs) of copper iodide (CuI) as an antibacterial agent has been presented. The nano particles are synthesized by co-precipitation method with an average size of 8 nm as determined by Transmission Electron Microscope (TEM). The average charge of the NPs is -21.5 mV at pH 7 as obtained by zeta potential measurement and purity is determined by XRD. These NPs are able to kill both gram positive and gram negative bacteria. Among the bacteria tested, DH5α is more sensitive but Bacillus subtilis is more resistant to NPs of CuI. Consequently, the MIC and MBC values of DH5α is least (0.066 mg/ml and 0.083 mg/ml respectively) and B. subtilis is highest (0.15 mg/ml and 0.18 mg/ml respectively) among the tested bacterial strains. From our studies it is inferred that CuI NPs produce reactive oxygen species (ROS) in both gram negative and gram positive bacteria and it also causes ROS mediated DNA damage for the suppression of transcription as revealed by reporter gene assay. Probably ROS is formed on the surface of NPs of CuI in presence of amine functional groups of various biological molecules. Furthermore they induce membrane damage as determined by atomic force microscopy (AFM). Thus production of ROS and membrane damage are major mechanisms of the bactericidal activity of these NPs of CuI.