Comprehensive review of the repositioning of non-oncologic drugs for cancer immunotherapy.

Drug repositioning or repurposing has gained worldwide attention as a plausible way to search for novel molecules for the treatment of particular diseases or disorders. Drug repurposing essentially refers to uncovering approved or failed compounds for use in various diseases. Cancer is a deadly disease and leading cause of mortality. The search for approved non-oncologic drugs for cancer treatment involved in silico modeling, databases, and literature searches. In this review, we provide a concise account of the existing non-oncologic drug molecules and their therapeutic potential in chemotherapy. The mechanisms and modes of action of the repurposed drugs using computational techniques are also highlighted. Furthermore, we discuss potential targets, critical pathways, and highlight in detail the different challenges pertaining to drug repositioning for cancer immunotherapy.

Multifunctional Nanocarriers for Alzheimer's Disease: Befriending the Barriers.

Neurodegenerative diseases (NDDs) have been increasing in incidence in recent years and are now widespread worldwide. Neuronal death is defined as the progressive loss of neuronal structure or function which is closely associated with NDDs and represents the intrinsic features of such disorders. Amyotrophic lateral sclerosis, frontotemporal dementia, Alzheimer's, Parkinson's, and Huntington's diseases (AD, PD, and HD, respectively) are considered neurodegenerative diseases that affect a large number of people worldwide. Despite the testing of various drugs, there is currently no available therapy that can remedy or effectively slow the progression of these diseases. Nanomedicine has the potential to revolutionize drug delivery for the management of NDDs. The use of nanoparticles (NPs) has recently been developed to improve drug delivery efficiency and is currently subjected to extensive studies. Nanoengineered particles, known as nanodrugs, can cross the blood-brain barrier while also being less invasive compared to the most treatment strategies in use. Polymeric, magnetic, carbonic, and inorganic NPs are examples of NPs that have been developed to improve drug delivery efficiency. Primary research studies using NPs to cure AD are promising, but thorough research is needed to introduce these approaches to clinical use. In the present review, we discussed the role of metal-based NPs, polymeric nanogels, nanocarrier systems such as liposomes, solid lipid NPs, polymeric NPs, exosomes, quantum dots, dendrimers, polymersomes, carbon nanotubes, and nanofibers and surfactant-based systems for the therapy of neurodegenerative diseases. In addition, we highlighted nanoformulations such as N-butyl cyanoacrylate, poly(butyl cyanoacrylate), D-penicillamine, citrate-coated peptide, magnetic iron oxide, chitosan (CS), lipoprotein, ceria, silica, metallic nanoparticles, cholinesterase inhibitors, an acetylcholinesterase inhibitors, metal chelators, anti-amyloid, protein, and peptide-loaded NPs for the treatment of AD.

Synthesis, Bioactivity Evaluation and Application of Plant-Based Nanoparticles.

Environmental and biomedical fields have various potential applications for the green synthesis of nanoparticles [...].

PARP in the neuropathogenesis of cytomegalovirus infection - Possible role and therapeutic perspective.

Cytomegalovirus infects the majority of the population globally. Congenital CMV infection acquired through primary maternal infection in pregnancy is the most common intrauterine infection with a high mortality rate due to severe long-term neurodevelopmental sequelae. The demyelination and neuroinflammation during CMV infection have been attributed to altered immune response and ROS-mediated apoptosis. PARP-1 protein is linked to apoptotic neuronal loss with subsequent neurotoxicity and CNS injury as a result of PARP hyperactivation. PARP-1 play a critical role in the establishment of latency including EBV, HHV-8 and HIV. Research on PARP inhibitors recently shows significant progress against neurodegenerative diseases such as Alzheimer's disease and cancer therapy including malignant lymphoma and hepatitis B virus-induced hepatocellular carcinoma. The role of PARP1 in the neuropathogenesis of CMV and the potential of PARP inhibitors in the prevention of neurological sequelae is still elusive. Further studies on the role of PARP on the neuropathogenesis of CMV infection can help thwart neurodegeneration through the potential development of PARP inhibitors such as small molecule inhibitors.

Synthesis, physicochemical characterization, and in vitro evaluation of biodegradable PLGA nanoparticles entrapped to folic acid for targeted delivery of kaempferitrin.

Polymeric nanoparticles are widely studied in the treatment of colorectal cancer. Kaempferitrin-loaded nontoxic and biodegradable poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) developed by the solvent emulsion evaporation method by improving its solubility and bioavailability. In order to improve the delivery of kaempferitrin (KM) to cancerous cells, folic acid (FA) combined kaempfertrin PLGA NPs were prepared. The goal of the study was whether PLGA NPs with surface KM and FA could help to prevent colorectal cancer. The synthesis of KM with FA in a nanomedicine could be crucial in the development of colon cancer chemotherapeutics. The physicochemical characteristics of synthesized KM-entrapped PLGA NPs were investigated by XRD, FTIR, zeta potential, and TEM. The KM + FA + PLGA NPs showed particle size with 132.9 ± 1.4 nm, zeta potential -15.0 ± 1.73 mV, encapsulation efficiency 67.92 ± 4.8, and drug-loading capacity 0.463 ± 0.173. In vitro cytotoxicity study on HT-29 cell lines using the MTT assay, the apoptotic study revealed that KM + FA + PLGA NPs have an enhanced cytotoxic effect compared to the KM + PLGA NPs drug solution. These findings suggested that KM + FA + PLGA NPs could be an effective chemotherapeutic drug delivery system in colon adenocarcinoma HT-29 cells.

Recent Insights and Multifactorial Applications of Carbon Nanotubes.

Nanotechnology has undergone significant development in recent years, particularly in the fabrication of sensors with a wide range of applications. The backbone of nanotechnology is nanostructures, which are determined on a nanoscale. Nanoparticles are abundant throughout the universe and are thought to be essential building components in the process of planet creation. Nanotechnology is generally concerned with structures that are between 1 and 100 nm in at least one dimension and involves the production of materials or electronics that are that small. Carbon nanotubes (CNTs) are carbon-based nanomaterials that have the structure of tubes. Carbon nanotubes are often referred to as the kings of nanomaterials. The diameter of carbon is determined in nanometers. They are formed from graphite sheets and are available in a variety of colors. Carbon nanotubes have a number of characteristics, including high flexibility, good thermal conductivity, low density, and chemical stability. Carbon nanotubes have played an important part in nanotechnology, semiconductors, optical and other branches of materials engineering owing to their remarkable features. Several of the applications addressed in this review have already been developed and used to benefit people worldwide. CNTs have been discussed in several domains, including industry, construction, adsorption, sensors, silicon chips, water purifiers, and biomedical uses, to show many treatments such as injecting CNTs into kidney cancers in rats, drug delivery, and directing a near-infrared laser at the cancers. With the orderly development of research in this field, additional therapeutic modalities will be identified, mainly for dispersion and densification techniques and targeted drug delivery systems for managing and curing posterior cortical atrophy. This review discusses the characteristics of carbon nanotubes as well as therapeutic applications such as medical diagnostics and drug delivery.

Organopesticides and fertility: where does the link lead to?

Organopesticides (OPs) are a group of various synthetic chemicals prevalently used in agriculture and homestead plantations. OPs were originally developed to remove insects, weeds, and other pests from agricultural fields for improving crop yields. Modern pesticides including organochlorine pesticides, organophosphorus pesticides, and amido-formyl ester are closely related to our lives. Many people are exposed to various OPs during farming practice. OPs can cause adverse effects and provoke serious impacts on normal reproductive functions of humans, resulting in loss of fertility. The effects of OPs in the reproductive system include association with fluctuation in the levels of sex hormones, delayed menstrual cycle, ovarian dysfunction, alteration in ovary weight, changes of follicle growth, altered oocyte feasibility, and changed the quality of spermatogenesis. Current literature clearly states that exposure to various OPs can impair the fertility of women and cause a high risk of reproductive potential. However, investigations on OPs exposure to woman fertility remain scarce. This review highlights effects of exposure to OPs on the fertility of occupational women and mechanisms of action involved in such effects on the reproductive function of women along with their related impacts.

Current Nanoparticle Approaches in Nose to Brain Drug Delivery and Anticancer Therapy - A Review.

Nanoparticles (NPs) are unique may be organic or inorganic, play a vital role in the development of drug delivery targeting the central nervous system (CNS). Intranasal drug delivery has shown to be an efficient strategy with attractive application for drug delivery to the CNS related diseases, such as Parkinson's disease, Alzheimer 's disease and brain solid tumors. Blood brain barrier (BBB) and blood-cerebrospinal fluid barriers are natural protective hindrances for entry of drug molecules into the CNS. Nanoparticles exhibit excellent intruding capacity for therapeutic agents and overcome protective barriers. By using nanotechnology based NPs targeted, drug delivery can be improved across BBB with discharge drugs in a controlled manner. NPs confer safe from degradation phenomenon. Several kinds of NPs are used for nose to the brain (N2B) enroute, such as lipidemic nanoparticles, polymeric nanoparticles, inorganic NPs, solid lipid NPs, dendrimers. Among them, popular lipidemic and polymeric NPs are discussed, and their participation in anti-cancer activity has also been highlighted in this review.

Exosomes: Current use and future applications.

Exosomes are endosomal-derived vesicles that play a critical role in cell-to-cell communication and are secreted in several biological fluids including serum, saliva, urine, ascites, and cerebro-spinal fluid amongst others. Exosomes are small (30-150 nm diameter) with a distinctive bilipid protein structure. They can carry and exchange various cargos between cells and are used as a non-invasive biomarker for several diseases. Exosomes are considered the best biomarkers for cancer diagnosis, owing to their unique characteristics. Here, we provide a review of the up-to-date applications of exosomes, derived from various sources, in the prognosis and diagnosis of several diseases including cancer, cardiovascular and regenerative diseases as well as, arthritis, neurological diseases, and diabetes mellitus. The role of exosomes and their applications in biomedical research and preclinical trials have also been briefly discussed.

Insights on the current status and advancement of diabetes mellitus type 2 and to avert complications: An overview.

Type 2 diabetes mellitus (T2DM) is an endocrine metabolic disorder, occurring worldwide due to aging, advancement in lifestyle by modernization. T2DM is characterized by higher levels of glucose in the blood due to unresponsive secretion of pancreatic insulin and insulin activity or altogether. T2DM is regarded as a powerful genetic susceptible disease that leads to high risk with insulin resistance and ß-cell dysfunction. To manage and overcome type 2 diabetes, physical activity, diet strategies, and other therapeutic medications along with usage of antiglycemic agents are developed and attempted appropriately. In the present review, attention has been focused on the understanding of T2DM outcomes, complications with possible management strategies, and pathophysiology of T2DM. Further, a detailed note on antiglycemic agents in use and other possible drugs of choice was discussed in the light of current preventive strategies are presented in this review.

Alleviation of Phytophthora infestans Mediated Necrotic Stress in the Transgenic Potato (Solanum tuberosum L.) with Enhanced Ascorbic acid Accumulation.

Potato is the most widely cultivated non-cereal crop in the world, and like any other crop, it is susceptible to yield losses because of various factors, including pathogen attacks. Among the various diseases of potato, late blight caused by the oomycete Phytophthora infestans is considered as the most devastating disease worldwide. In this study, transgenic potato plants overexpressing the D-galacturonic acid reductase (GalUR) gene with an enhanced level of cellular L-ascorbate (L-AsA) were challenged with Phytophthora infestans to determine the level of stress tolerance induced in those plants. With the onset of pathogen infection, necrotic lesions progressively expanded and became necrotic in the control plants. The transgenic potato lines with enhanced ascorbic acid showed reduced necrotic lesions. Hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels were relatively lower in transgenic plants compared to the untransformed control (UT) plants. The mRNA expressions of pathogenesis-related (PR) genes, such as pathogenesis related 1 (PR1) and phenylalanine ammonia-lyase (PAL) were slightly higher in GalUR overexpressing transgenic lines as compared to the untransformed control plants. Pathogen infection also altered the mRNA expression of genes associated with gibberellic acid (GA) and abscisic acid (ABA) biosynthesis. Furthermore, the increase in various antioxidant enzymes was also observed in the gene expression analysis with the transgenic plants. The complete loss of the pathogen growth and disease occurrence was not observed in our study; however, the findings indicated that an increase in the level of cellular L-ascorbate in the transgenic potato leads to enhanced cellular antioxidants, PR genes and plant defense hormones, such as GA and ABA resulting in the reduction of the disease symptoms caused by the Phytophthora infestans.

Synthesis, characterization and pharmacological potential of green synthesized copper nanoparticles.

The phenomenal and astonishing properties and their different application in the field of pharmaceutical made copper nanoparticles (Cu-NPs) to be in the spotlight of the researcher's focus. In the present study, copper nanoparticles were biologically synthesized with the aqueous extract of the flower Millettia pinnata, and their corresponding characteristics were studied using UV-visible spectroscopy, XRD, FT-IR, SEM, TEM, and SAED analysis. Copper acetate was reduced to copper nanoparticles and is confirmed by UV-visible spectrophotometer analysis. The maximum absorption occurring at 384 nm at the visible spectrum of UV rays confirms the surface plasmon resonance of the nanoparticles. The result of the FTIR spectroscopy analysis of the nanoparticles complements the involvement of organic mioties of the flower extract in the synthesis. The synthesized particles were extremely durable, spherical with the average particle size in the range of 23 ± 1.10 nm. The Cu-NPs exhibited greater inhibition on DPPH radical and nitric oxide scavenging activities. The biologically synthesized Cu-NPs was receptive to the Gram-negative and Gram-positive bacteria as well. The Cu-NPs exhibited strong anti-inflammatory activity using albumin denaturation and membrane stabilization. The present study is the first effort done to synthesize of Cu-NPs from the extract of M. pinnata flower. Consequently, to authenticate the results and to establish the antioxidant, antibacterial, an anti-diabetic and anti-inflammatory agent, in vivo studies are made in the molecular level.

Evaluation of Polyphenolic Compounds and Pharmacological Activities in Hairy Root Cultures of Ligularia fischeri Turcz. f. spiciformis (Nakai).

A considerable amount of bioactive compounds have been used for the biopharmaceutical engineering to help human health and nutrition. Hairy root culture (HRC) or transgenic root is a favourable alternative technique for phytochemical production. Ligularia fischeri is a significant source of pharmaceutically important active compounds with an enormous range of health care applications. HRC of L. fischeri was developed using Agrobacterium rhizogenes for the production of polyphenolic compounds with antioxidant, antimicrobial, antidiabetic, anticancer and anti-inflammatory pharmaceutical activities. Hairy roots (HRs) were selected by morphological assessment, genetic and molecular analyses. The maximum accumulation of fresh mass (94.15 g/L) and dry mass (9.45 g/L) was recorded in MS liquid medium supplemented with 30 g/L sucrose at 28 days. Furthermore, HRs successfully produced numerous polyphenolic compounds, including six hydroxycinnamic acids, seven flavonols, seven hydroxybenzoic acids, vanillin, resveratrol, pyrogallol, homogentisic, and veratric acids, which were identified by UHPLC analysis. HRs produced higher total phenolic (185.65 mg/g), and flavonoid (5.25 mg/g) contents than non-transformed roots (125.55 mg/g and 3.75 mg/g). As a result of these metabolic changes, pharmaceutical activities were found higher in HRs than non-transformed roots (NTRs). The present study indicates that HRC has the potential to increase the content of beneficial polyphenolic compounds with higher potential pharmaceutical activities. To the best of our knowledge, the present study is the first report on enhancing the production of polyphenolic compounds with pharmaceutical activities from the HRCs of L. fischeri.

Elicitation of silver nanoparticles enhanced the secondary metabolites and pharmacological activities in cell suspension cultures of bitter gourd.

This study describes the influence of bio-synthesized silver nanoparticles (AgNPs) on phytochemicals and their pharmacological activities in the cell suspension cultures (CSC) of bitter gourd. To standardize the effect of sucrose, plant growth regulators, medium, AgNPs and growth kinetics for the biomass and bioactive compounds accumulation in CSC of bitter gourd. The medium comprising MS salts, sucrose (30 g/L) with 2,4-D (1.0 mg/L) and TDZ (0.1 mg/L) at 28 days of CSC was appropriate for biomass and bioactive compound accumulation. The contents of silver, malondialdehyde and hydrogen peroxide were highly elevated in AgNPs (10 mg/L)-elicited CSC when compared with non-elicited CSC. AgNPs (5 mg/L) elicited CSC extracts had significantly enhanced the production of total phenolic (3.5 ± 0.2 mg/g), and flavonoid (2.5 ± 0.06 mg/g) contents than in the control CSC extracts (2.5 ± 0.1 and 1.6 ± 0.05 mg/g). AgNPs (5 mg/L) elicited CSC showed a higher amount of flavonols (1822.37 µg/g), hydroxybenzoic (1713.40 µg/g) and hydroxycinnamic (1080.10 µg/g) acids than the control CSC (1199, 1394.42 and 944.52 µg/g, respectively). Because of these metabolic changes, the pharmacological activities (antioxidant, antidiabetic, antibacterial, antifungal and anticancer) were high in the AgNPs (5 mg/L)-elicited CSC extracts in bitter gourd. The study suggested the effectiveness of elicitation process in enhancing the accumulation of phenolic compounds and pharmacological activities. AgNPs-elicited CSC offered an effective and favorable in vitro method to improve the production of bioactive compounds for potential uses in pharmaceutical industries.

Influence of silver nanoparticles on the enhancement and transcriptional changes of glucosinolates and phenolic compounds in genetically transformed root cultures of Brassica rapa ssp. rapa.

Glucosinolates (GSLs) and phenolic compounds (PCs) are biologically active and involved in the defense reaction of plants; these compounds have a beneficial effect on human health. In this study, we described the influence of biologically synthesized silver nanoparticles (Ag NPs) to enhance the phytochemicals (GSLs and PCs), their transcription levels, and their biological activities in genetically transformed root cultures (hairy root cultures) of Brassica rapa. The concentrations of silver and reactive oxygen species (malondialdehyde and hydrogen peroxide) were highly elevated in the Ag NP-elicited hairy roots (HRs). Glucosinolates (glucoallysin, glucobrassicanapin, sinigrin, progoitrin, gluconapin, 4-methoxyglucobrassicin, 4-hydroxyglucobrassicin, glucobrassicin, neoglucobrassicin, and gluconasturtiin) and their transcripts (MYB34, MYB51, MYB28, and MYB29) were significantly enhanced in the Ag NP-elicited HRs. Moreover, the phenolic compounds (flavonols, hydroxybenzoic, and hydroxycinnamic acids) were significantly enriched in the Ag NP-elicited HRs. Total phenolic and flavonoid concentrations and their transcripts (PAL, CHI, and FLS) were higher in the Ag NP-elicited HRs than in the non-elicited HRs. Additionally, biological (antioxidant, antimicrobial, and anticancer) activities were significantly higher in the Ag NP-elicited HRs than in the non-elicited HRs. The Ag NP-elicited HR cultures offered an efficient and promising in vitro method to increase the production of health-promoting bioactive compounds, which may be useful in nutraceutical and pharmaceutical industries.

Effect of silver nanoparticles on phenolic compounds production and biological activities in hairy root cultures of Cucumis anguria.

The present study describes the elicitor effect of silver ion (Ag+) and biologically synthesized silver nanoparticles (AgNPs) to enhance the biomass accumulation and phenolic compound production as well as biological activities (antioxidant, antimicrobial and anticancer) in genetically transformed root (hairy root) cultures of Cucumis anguria. The biomass of hairy root cultures was significantly increased by AgNPs whereas decreased in Ag+ elicitation at 1 and 2 mg/L. AgNPs-elicited hairy roots produced a significantly higher amount of individual phenolic compounds (flavonols, hydroxycinnamic and hydroxybenzoic acids), total phenolic and flavonoid contents than Ag+-elicited hairy roots. Moreover, antioxidant, antimicrobial and anticancer activities were significantly higher following AgNPs-elicitation compared with that in Ag+-elicited hairy roots. We suggest that AgNPs could be an efficient elicitor in hairy root cultures to increase the phytochemical production.

Nanotechnology: current uses and future applications in the food industry.

Recent advances in nanoscience and nanotechnology intend new and innovative applications in the food industry. Nanotechnology exposed to be an efficient method in many fields, particularly the food industry and the area of functional foods. Though as is the circumstance with the growth of any novel food processing technology, food packaging material, or food ingredient, additional studies are needed to demonstrate the potential benefits of nanotechnologies and engineered nanomaterials designed for use in foods without adverse health effects. Nanoemulsions display numerous advantages over conventional emulsions due to the small droplets size they contain: high optical clarity, excellent physical constancy against gravitational partition and droplet accumulation, and improved bioavailability of encapsulated materials, which make them suitable for food applications. Nano-encapsulation is the most significant favorable technologies having the possibility to ensnare bioactive chemicals. This review highlights the applications of current nanotechnology research in food technology and agriculture, including nanoemulsion, nanocomposites, nanosensors, nano-encapsulation, food packaging, and propose future developments in the developing field of agrifood nanotechnology. Also, an overview of nanostructured materials, and their current applications and future perspectives in food science are also presented.

Green approach for synthesis of zinc oxide nanoparticles from Andrographis paniculata leaf extract and evaluation of their antioxidant, anti-diabetic, and anti-inflammatory activities.

Bio-mediated synthesis of zinc oxide nanoparticles (ZnO NPs) was carried out by utilizing the reducing and capping potential of Andrographis paniculata leaf extract. The capped ZnO NPs were characterized using UV-Vis, XRD, FTIR, SEM, TEM and SAED analyses. FTIR analysis suggested the role of phenolic compounds, terpenoids, and proteins of A. paniculata leaf extract, in nucleation and stability of ZnO NPs. XRD pattern compared with the standard confirmed spectrum of zinc oxide particles formed in the present experiments were in the form of nanocrystals, as evidenced by the peaks at 2θ values. SEM and TEM analysis of ZnO NPs reveals those spherical and hexagonal shapes and the sizes at the range of 96-115 and 57 ± 0.3 nm, respectively. The synthesized nanoparticles possess strong biological activities regarding anti-oxidant, anti-diabetic, and anti-inflammatory potentials which could be utilized in various biological applications by the cosmetic, food and biomedical industries.

Novel and environmental friendly approach; Impact of Neem (Azadirachta indica) gum nano formulation (NGNF) on Helicoverpa armigera (Hub.) and Spodoptera litura (Fab.).

The future of this study was to prepare a natural pesticide which will not harm the environment and yet control pests. Neem gum nano formulation (NGNF), a novel biopesticide prepared from the Neem gum extract (Azadirachta indica) (NGE) was evaluated for its antifeedant, larvicidal and pupicidal activities against Helicoverpa armigera (Hub.) and Spodoptera litura (Fab.) at 100ppm. The NGNF showed significant (100%) antifeedant, larvicidal and pupicidal activities against H. armigera and S. litura. The LC50 values of 10.20, 12.49 and LC90 values of 32.68, 36.68ppm on H. armigera and S. litura, respectively at 100ppm. The NGNF treatments showed differences in the activities of detoxifying enzymes, carboxylesterases, glucosidases and glutathione S-transferases in the larval gut. Earthworm toxicity illustrated that 6.25ppm of chemical insecticides (cypermethrin) varied widely in their contact toxicities compared to 100ppm of NGNF and control in both contact filter paper and artificial soil test. The NGNF were characterized and confirmed by FTIR, XRD, SEM and EDX analysis. Ten compounds were identified from the Neem gum extract (NGE) by Gas Chromatography-Mass Spectrometry (GC-MS) analysis. The major compounds were fatty acids like Hexadecanoic acid, oleic acid, and ricinoleic acid. NGNF could be used as an agent to prepare novel bio-pesticides formulations.