Down Regulation of Osteocalcin Gene in Chickens Treated with Cadmium

Background: Cadmium is one of the heavy metals with harmful effects on different body organs and systems. The aim of this study was to investigate the harmful effects of cadmium, as a heavy metal, on the histological structure of bone and the expression of osteocalcin gene. Methods: Forty chickens were obtained, anesthetized and their femurs were surgically removed. The real time polymerase chain reaction (PCR) was used to study the osteocalcin gene expression. Results: The osteocalcin gene expression rate were: 1.000± 0.1; 0.86± 0.01; 0.63± 0.09, and 0.41± 0.06 in the controls, experiment I, experiment II and experiment III groups, respectively (P < 0.05). Also, the nuclear pyknosis in osteocytes and decreased bone formation were observed in the histology slides of the chicken bones. Conclusions: We conclude that cadmium adversely affected the chicken bones as evident by the decreased osteocalcin gene expression and the adverse effects on the bone histology. We recommend that plans be developed to prevent the outbreak of cadmium and other heavy metals in animal and human environment

MicroRNA-mediated regulation of Nrf2 signaling pathway: Implications in disease therapy and protection against oxidative stress

MicroRNAs (miRs) are small non-coding pieces of RNA that are involved in a variety of physiologic processes such as apoptosis, cell proliferation, cell differentiation, cell cycle and cell survival. These multifunctional nucleotides are also capable of preventing oxidative damages by modulating antioxidant defense systems in a variety of milieu, such as in diabetes. Although the exact molecular mechanisms by which miRs modulate the antioxidant defense elements are unclear, some evidence suggests that they may exert these effects via nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. This intracellular mechanism is crucial in the maintenance of the physiologic redox balance by regulating the expression and activity of various cellular antioxidative defense elements and thereby plays a pivotal role in the development of oxidative stress. Any impairment in the Nrf2 signaling pathway may result in oxidative damage-dependent complications such as various diabetic complications, neurological disorders and cancer. In the current review, we discuss the modulatory effects of miRs on the Nrf2 signaling pathway, which can potentially be novel therapeutic targets

Pyrazole-based analogs as potential antibacterial agents against methicillin-resistance staphylococcus aureus (MRSA) and its SAR elucidation

Methicillin-resistant Staphylococcus aureus (MRSA) is becoming lethal to humanity due to easy transmission and difficult-to-treat skin and flimsy diseases. The most threatening aspect is the rapid resistance development of MRSA to any approved antibiotics, including vancomycin. The development of new, efficient, and nontoxic drug candidate to fight against MRSA isolates is the need of the hour. The intriguing molecular structure and versatile bioactive pyrazole core attracting to development required novel antibiotics. This review presents the decade developments of pyrazole-containing derivatives with a broad antibacterial movement against diverged bacterial strains. In specific, we correlated the efficacy of structurally diversified pyrazole analogs against MRSA and discussed different angles of structure-activity relationship (SAR). The current survey highlights pyrazole hybrids' present scenario on MRSA studies, covering articles published from 2011 to 2020. This collective information may become an excellent platform to plan and develop new pyrazole-based small MRSA growth inhibitors with minimal side effects. (C) 2020 Elsevier Masson SAS. All rights reserved

Multifunctional polymeric nanoplatforms for brain diseases diagnosis, therapy and theranostics

The blood–brain barrier (BBB) acts as a barrier to prevent the central nervous system (CNS) from damage by substances that originate from the blood circulation. The BBB limits drug penetration into the brain and is one of the major clinical obstacles to the treatment of CNS diseases. Nanotechnology-based delivery systems have been tested for overcoming this barrier and releasing related drugs into the brain matrix. In this review, nanoparticles (NPs) from simple to developed delivery systems are discussed for the delivery of a drug to the brain. This review particularly focuses on polymeric nanomaterials that have been used for CNS treatment. Polymeric NPs such as polylactide (PLA), poly (D, L-lactide-co-glycolide) (PLGA), poly (ε-caprolactone) (PCL), poly (alkyl cyanoacrylate) (PACA), human serum albumin (HSA), gelatin, and chitosan are discussed in detail

Functionalization of polymers and nanomaterials for water treatment, food packaging, textile and biomedical applications: a review

AbstractThe inert nature of most commercial polymers and nanomaterials results in limitations of applications in various industrial fields. This can be solved by surface modifications to improve physicochemical and biological properties, such as adhesion, printability, wetting and biocompatibility. Polymer functionalization allows to graft specific moieties and conjugate molecules that improve material performances. In the last decades, several approaches have been designed in the industry and academia to graft functional groups on surfaces. Here, we review surface decoration of polymers and nanomaterials, with focus on major industrial applications in the medical field, textile industry, water treatment and food packaging. We discuss the advantages and challenges of polymer functionalization. More knowledge is needed on the biology behind cell–polymer interactions, nanosafety and manufacturing at the industrial scale

Chitosan-based advanced materials for docetaxel and paclitaxel delivery: Recent advances and future directions in cancer theranostics

Paclitaxel (PTX) and docetaxel (DTX) are key members of taxanes with high anti-tumor activity against various cancer cells. These chemotherapeutic agents suffer from a number of drawbacks and it seems that low solubility in water is the most important one. Although much effort has been made in improving the bioavailability of PTX and DTX, the low bioavailability and minimal accumulation at tumor sites are still the challenges faced in PTX and DTX therapy. As a consequence, bio-based nanoparticles (NPs) have attracted much attention due to unique properties. Among them, chitosan (CS) is of interest due to its great biocompatibility. CS is a positively charged polysaccharide with the capability of interaction with negatively charged biomolecules. Besides, it can be processed into the sheet, micro/nano-particles, scaffold, and is dissolvable in mildly acidic pH similar to the pH of the tumor microenvironment. Keeping in mind the different applications of CS in the preparation of nanocarriers for delivery of PTX and DTX, in the present review, we demonstrate that how CS functionalized-nanocarriers and CS modification can be beneficial in enhancing the bioavailability of PTX and DTX, targeted delivery at tumor site, image-guided delivery and co-delivery with other anti-tumor drugs or genes

Chitosan-based nanoscale systems for doxorubicin delivery:Exploring biomedical application in cancer therapy

Abstract Green chemistry has been a growing multidisciplinary field in recent years showing great promise in biomedical applications, especially for cancer therapy. Chitosan (CS) is an abundant biopolymer derived from chitin and is present in insects and fungi. This polysaccharide has favorable characteristics, including biocompatibility, biodegradability, and ease of modification by enzymes and chemicals. CS‐based nanoparticles (CS‐NPs) have shown potential in the treatment of cancer and other diseases, affording targeted delivery and overcoming drug resistance. The current review emphasizes on the application of CS‐NPs for the delivery of a chemotherapeutic agent, doxorubicin (DOX), in cancer therapy as they promote internalization of DOX in cancer cells and prevent the activity of P‐glycoprotein (P‐gp) to reverse drug resistance. These nanoarchitectures can provide co‐delivery of DOX with antitumor agents such as curcumin and cisplatin to induce synergistic cancer therapy. Furthermore, co‐loading of DOX with siRNA, shRNA, and miRNA can suppress tumor progression and provide chemosensitivity. Various nanostructures, including lipid‐, carbon‐, polymeric‐ and metal‐based nanoparticles, are modifiable with CS for DOX delivery, while functionalization of CS‐NPs with ligands such as hyaluronic acid promotes selectivity toward tumor cells and prevents DOX resistance. The CS‐NPs demonstrate high encapsulation efficiency and due to protonation of amine groups of CS, pH‐sensitive release of DOX can occur. Furthermore, redox‐ and light‐responsive CS‐NPs have been prepared for DOX delivery in cancer treatment. Leveraging these characteristics and in view of the biocompatibility of CS‐NPs, we expect to soon see significant progress towards clinical translation

Autophagy modulators : mechanistic aspects and drug delivery systems

Funding: this work was supported by a grant from NMRC-CIRG to CTY. APK was supported by grants from National Medical Research Council of Singapore, NCIS Yong Siew Yoon Research Grant through donations from the Yong Loo Lin Trust and by the National Research Foundation Singapore and the Singapore Ministry of Education under its Research Centers of Excellence initiative to Cancer Science Institute of Singapore, National University of Singapore. R.M. acknowledges financial supports of Kerman University of Medical Sciences.Autophagy modulation is considered to be a promising programmed cell death mechanism to prevent and cure a great number of disorders and diseases. The crucial step in designing an effective therapeutic approach is to understand the correct and accurate causes of diseases and to understand whether autophagy plays a cytoprotective or cytotoxic/cytostatic role in the progression and prevention of disease. This knowledge will help scientists find approaches to manipulate tumor and pathologic cells in order to enhance cellular sensitivity to therapeutics and treat them. Although some conventional therapeutics suffer from poor solubility, bioavailability and controlled release mechanisms, it appears that novel nanoplatforms overcome these obstacles and have led to the design of a theranostic-controlled drug release system with high solubility and active targeting and stimuli-responsive potentials. In this review, we discuss autophagy modulators-related signaling pathways and some of the drug delivery strategies that have been applied to the field of therapeutic application of autophagy modulators. Moreover, we describe how therapeutics will target various steps of the autophagic machinery. Furthermore, nano drug delivery platforms for autophagy targeting and co-delivery of autophagy modulators with chemotherapeutics/siRNA, are also discusse

The ER Stress/UPR Axis in Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis.

Cellular protein homeostasis in the lungs is constantly disrupted by recurrent exposure to various external and internal stressors, which may cause considerable protein secretion pressure on the endoplasmic reticulum (ER), resulting in the survival and differentiation of these cell types to meet the increased functional demands. Cells are able to induce a highly conserved adaptive mechanism, known as the unfolded protein response (UPR), to manage such stresses. UPR dysregulation and ER stress are involved in numerous human illnesses, such as metabolic syndrome, fibrotic diseases, and neurodegeneration, and cancer. Therefore, effective and specific compounds targeting the UPR pathway are being considered as potential therapies. This review focuses on the impact of both external and internal stressors on the ER in idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) and discusses the role of the UPR signaling pathway activation in the control of cellular damage and specifically highlights the potential involvement of non-coding RNAs in COPD. Summaries of pathogenic mechanisms associated with the ER stress/UPR axis contributing to IPF and COPD, and promising pharmacological intervention strategies, are also presented

Resveratrol Modulates Transforming Growth Factor-Beta (TGF-β) Signaling Pathway for Disease Therapy: A New Insight into Its Pharmacological Activities

Resveratrol (Res) is a well-known natural product that can exhibit important pharmacological activities such as antioxidant, anti-diabetes, anti-tumor, and anti-inflammatory. An evaluation of its therapeutic effects demonstrates that this naturally occurring bioactive compound can target different molecular pathways to exert its pharmacological actions. Transforming growth factor-beta (TGF-&beta;) is an important molecular pathway that is capable of regulating different cellular mechanisms such as proliferation, migration, and angiogenesis. TGF-&beta; has been reported to be involved in the development of disorders such as diabetes, cancer, inflammatory disorders, fibrosis, cardiovascular disorders, etc. In the present review, the relationship between Res and TGF-&beta; has been investigated. It was noticed that Res can inhibit TGF-&beta; to suppress the proliferation and migration of cancer cells. In addition, Res can improve fibrosis by reducing inflammation via promoting TGF-&beta; down-regulation. Res has been reported to be also beneficial in the amelioration of diabetic complications via targeting the TGF-&beta; signaling pathway. These topics are discussed in detail in this review to shed light on the protective effects of Res mediated via the modulation of TGF-&beta; signaling