Rosacea Topical Treatment and Care: From Traditional to New Drug Delivery Systems.

Rosacea is a multifactorial chronic inflammatory dermatosis characterized by flushing, nontransient erythema, papules and pustules, telangiectasia, and phymatous alterations accompanied by itching, burning, or stinging, the pathophysiology of which is not yet fully understood. Conventional topical treatments usually show limited efficacy due to the physical barrier property of the skin that hinders skin penetration of the active ingredients, thereby hampering proper drug skin delivery and the respective therapeutic or cosmetic effects. New advances regarding the physiopathological understanding of the disease and the underlying mechanisms suggest the potential of new active ingredients as promising therapeutic and cosmetic approaches to this dermatosis. Additionally, the development of new drug delivery systems for skin delivery, particularly the potential of nanoparticles for the topical treatment and care of rosacea, has been described. Emphasis has been placed on their reduced nanometric size, which contributes to a significant improvement in the attainment of targeted skin drug delivery. In addition to the exposition of the known pathophysiology, epidemiology, diagnosis, and preventive measures, this Review covers the topical approaches used in the control of rosacea, including skin care, cosmetics, and topical therapies, as well as the future perspectives on these strategies.

Cardioprotective effect of silicon-built restraint device (ASD), for left ventricular remodeling in rat heart failure model.

This study aims to evaluate the feasibility and cardio-protective effects of biocompatible silicon-built restraint device (ASD) in the rat's heart failure (HF) model. The performance and compliance characteristics of the ASD device were assessed in vitro by adopting a pneumatic drive and ball burst test. Sprague-Dawley (SD) rats were divided into four groups (n = 6); control, HF, HF + CSD, and HF + ASD groups, respectively. Heart failure was developed by left anterior descending (LAD) coronary artery ligation in all groups except the control group. The ASD and CSD devices were implanted in the heart of HF + ASD and HF + CSD groups, respectively. The ASD's functional and expansion ability was found to be safe and suitable for attenuating ventricular remodeling. ASD-treated rats showed normal heart rhythm, demonstrated by smooth -ST and asymmetrical T-wave. At the same time, hemodynamic parameters of the HF + ASD group improved systolic and diastolic functions, reducing ventricular wall stress, which indicated reverse remodeling. The BNP values were reduced in the HF + ASD group, which confirmed ASD feasibility and reversed remodeling at a molecular level. Furthermore, the HF + ASD group with no fibrosis suggests that ASD has significant curative effects on the heart muscles. In conclusion, ASD was found to be a promising restraint therapy than the previously standard restraint therapies. Stepwise ASD fabrication process (a) 3D computer model of ASD was generated by using Rhinoceros 5.0 software (b) 3D blue wax model of ASD (c) Silicon was prepared by mixing the solutions (as per manufacturer instruction) (d) Blue wax model of ASD was immersed into liquid Silicon (e) ASD model was put into the oven for 3 hours at 50 °C. (f) Blue wax started melting from the ASD model (g) ASD model was built from pure silicon (h) Two access lines were linked to the ASD device, which was connected with an implantable catheter (Port-a-cath), scale bar 100 µm. (Nikon Ldx 2.0).

Gut-Thyroid axis: How gut microbial dysbiosis associated with euthyroid thyroid cancer.

Thyroid cancer in humans has a fast-growing prevalence, with the most common lethal endocrine malignancy for unknown reasons. The current study was aimed to perform qualitative and quantitative investigation and characterization of the gut bacterial composition of euthyroid thyroid cancer patients. The fecal samples were collected from sixteen euthyroid thyroid cancer patients and ten from healthy subjects. The PCR-DGGE was conducted by targetting the V3 region of 16S rRNA gene, as well as real-time PCR for Bacteroides vulgatus, E.coli Bifidobacterium, Clostridium leptum and Lactobacillus were carried. High-throughput sequencing of V3+V4 region of 16S rRNA gene was performed on Hiseq 2500 platform on 20 (10 healthy & 10 diseased subjects) randomly selected fecal samples. The richness indices and comparative diversity analysis showed significant gut microbial modification in euthyroid thyroid cancer than control. At phylum level, there was significant enrichment of Firmicutes, Verrucomicrobia, while a significant decrease in Bacteroidetes was detected in the experimental group. At family statistics, significant high levels of Ruminococcaceae and Verrucomicrobiaceae, while the significant lower abundance of Bacteroidaceae, Prevotellaceae, Porphyromonadaceae, and Alcaligenaceae was after observed. It also found that the significantly raised level of Escherichia-Shigella, Akkermansia [Eubacterium]_coprostanoligenes, Dorea, Subdoligranulum, and Ruminococcus_2 genera, while significantly lowered genera of the patient group were Prevotella_9, Bacteroides and Klebsiella. The species-level gut microbial composition showed a significantly raised level of Escherichia coli in euthyroid thyroid cancer. Thus, this study reveals that euthyroid thyroid cancer patients have significant gut microbial dysbiosis. Moreover, Statistics (P<0.05) of each gut microbial taxa were significantly changed in euthyroid thyroid cancer patients. Therefore, the current study may propose new approaches to understanding thyroid cancer patients' disease pathways, mechanisms, and treatment.

Gut microbial dysbiosis and its association with esophageal cancer.

Due to its aggressive nature and low survival rate, esophageal cancer is one of the deadliest cancer. While the intestinal microbiome significantly influences human health and disease. This research aimed to investigate and characterize the relative abundance of intestinal bacterial composition in esophageal cancer patients. The fecal samples were collected from esophageal cancer patients (n = 15) and healthy volunteers (n = 10). The PCR-DGGE was carried out by focusing on the V3 region of the 16S rRNA gene, and qPCR was performed for Bacteroides vulgatus, Escherichia coli, Bifidobacterium, Clostridium leptum and Lactobacillus. High-throughput sequencing of the 16S rRNA gene targeting the V3+V4 region was performed on 20 randomly selected samples. PCR-DGGE and High-throughput diversity results showed a significant alteration of gut bacterial composition between the experimental and control groups, which indicates the gut microbial dysbiosis in esophageal cancer patients. At the phylum level, there was significant enrichment of Bacteroidetes, while a non-significant decrease of Firmicutes in the experimental group. At family statistics, a significantly higher level of Bacteroidaceae and Enterobacteriaceae, while a significantly lower abundance of Prevotellaceae and Veillonellaceae were observed. There was a significantly high prevalence of genera Bacteroides, Escherichia-Shigella, while a significantly lower abundance of Prevotella_9 and Dialister in the experimental group as compared to the control group. Furthermore, the species analysis also showed significantly raised level of Bacteroides vulgatus and Escherichia coli in the experimental group. These findings revealed a significant gut microbial dysbiosis in esophageal cancer patients. So, the current study can be used for the understanding of esophageal cancer treatment, disease pathway, mechanism, and probiotic development.

Delivery strategies of amphotericin B for invasive fungal infections.

Invasive fungal infections (IFIs) represent a growing public concern for clinicians to manage in many medical settings, with substantial associated morbidities and mortalities. Among many current therapeutic options for the treatment of IFIs, amphotericin B (AmB) is the most frequently used drug. AmB is considered as a first-line drug in the clinic that has strong antifungal activity and less resistance. In this review, we summarized the most promising research efforts on nanocarriers for AmB delivery and highlighted their efficacy and safety for treating IFIs. We have also discussed the mechanism of actions of AmB, rationale for treating IFIs, and recent advances in formulating AmB for clinical use. Finally, this review discusses some practical considerations and provides recommendations for future studies in applying AmB for combating IFIs.

Self-assembled nanomedicine combining a berberine derivative and doxorubicin for enhanced antitumor and antimetastatic efficacy via mitochondrial pathways.

Mitochondria play a central role in cancer progression and tumor metastasis, and nanomedicines targeting mitochondria have emerged as a promising strategy for tumor therapy. However, mitochondria targeting strategies have not been widely explored in the inhibition of tumor metastasis, and they have disadvantages of complicated preparation, low drug loading, systemic toxicity of the carriers and poor accumulation at tumor sites. Here we firstly developed self-assembled nanodrugs with a high drug loading (∼68%) comprised of a berberine derivative (Ber) and doxorubicin (Dox) by a simple nano-precipitation method, which successfully altered the target location of Dox from the nucleus to mitochondria and therefore inhibited the proliferation, invasion and migration of MDA-MB-231 cells by triggering cell apoptosis. The surface of nanodrugs was modified with DSPE-PEG-folic acid (DSPE-PEG-FA) and hyaluronic acid (HA) for precise tumor recognition and enhanced accumulation (HA-FA-BD NDs). Upon arrival at the tumor site with the help of the enhanced permeability and retention (EPR) effect, the partial degradation of HA by hyaluronidase (HAase) at the tumor site allowed the partial exposure of the positively charged FA-BD NDs to the cells, then nanodrugs would accumulate and enter tumor cells by dual binding to both folic acid (FA) and CD-44 receptors. Once internalized into lysosomes, both the HA outer shell and DSPE-PEG-FA of nanodrugs were degraded or decomposed completely to expose positively charged BD NDs. Driven by delocalized lipophilic cations, nanodrugs could escape from lysosomes and reach mitochondria to induce a cascade reaction and finally cell apoptosis, as well as suppressing matrix metalloprotease (MMP)-2 and -9 activities and finally cell migration and invasion. In a xenograft mice model of MDA-MB-231 breast cancer cells, the nanodrugs repaired the defects in Mfn 1/Drp 1 mitochondrial proteins, suppressed the activity of MMP-2 and -9, and significantly inhibited tumor cell proliferation and pulmonary metastasis. Our study showed a promising strategy for the treatment of metastatic breast cancer by targeting mitochondria followed by enhanced apoptosis.

Virus-Mimicking Mesoporous Silica Nanoparticles with an Electrically Neutral and Hydrophilic Surface to Improve the Oral Absorption of Insulin by Breaking Through Dual Barriers of the Mucus Layer and the Intestinal Epithelium.

Protein and peptide drugs orally suffer from extremely low bioavailability principally for the complicated gastrointestinal environment along with the difficulty of passing through the mucus layer and the underlying epithelium. In our work, we fabricated mesoporous silica nanoparticles with modification groups (MSN-NH2@COOH/CPP5) that effectively penetrated the mucus layer and passed through the intestinal epithelium by mimicking the virus surface. Naked nanoparticles were prepared with inner pores of 6 nm diameter to allow efficient insulin loading and coated with the cationic cell-penetrating KLPVM peptide and the anionic glutaric anhydride to yield hydrophilic MSN-NH2@COOH/CPP5 with a ζ-potential of -0.49 mV. The apparent permeability coefficient of virus-mimicking nanoparticles was 14.61 × 10-5 cm/s. The virus-mimicking nanoparticles showed dramatically lower binding to mucin and faster penetration of the mucus layer than positively charged nanoparticles (MSN@NH2) with a ζ-potential of +35.00 mV. The KLPVM peptide enhanced the uptake of MSN-NH2@COOH/CPP5 by coculturing Caco-2 and E12 cells as an intestinal epithelium model. MSN-NH2@COOH/CPP5 enhanced apical-to-basal transcytosis for being internalized primarily through caveolae-mediated endocytosis. Indeed, for MSN-NH2@COOH/CPP5, the transepithelial transport of the Caco-2 cell monolayer was 2.4-fold higher than MSN@NH2 and 2.0-fold higher than MSN-NH2@COOH. In vitro, loading insulin into nanoparticles maintained the bioactivity of the protein under simulated intestinal conditions. Insulin loaded into MSN-NH2@COOH/CPP5 reduced the diabetic rats' blood glucose level by nearly 50%. The bioavailability of insulin encapsulated in the MSN-NH2@COOH/CPP5 nanoparticles was 2.1-fold more than insulin when administered directly into the jejunum. Nanoparticles with modifications indicated no significant toxicity in in vitro or in vivo preliminary studies. The obstacles of the mucus layer and intestinal epithelium may be effectively conquered by these virus-mimicking nanoparticles for oral delivery of protein and peptide drugs.

Preparation and characterization of bear bile-loaded pH sensitive in-situ gel eye drops for ocular drug delivery.

OBJECTIVES: In this study, a stable bear bile-loaded pH sensitive in-situ eye drop gel was prepared for sustain delivery and enhanced therapeutic application. MATERIALS AND METHODS: Bear bile-loaded in-situ ocular gels with different Carbopol/Hydroxypropyl methylcellulose (HPMC) ratios were prepared and their stability was tested in PBS at a series of pH at 40 °C. The morphology was observed by SEM examination and rheology was observed by Rheometer equipped with a 60-mm cone-plate at apex angle of 1°. Gel erosion and release kinetics of Tauroursodeoxycholic acid (TUDCA) was determined by HPLC. While, the in vivo dwelling time was obtained after administering the fluorescent-loaded gel in ocular disease-free New Zealand rabbits. Finally, biocompatibility and toxicity was observed by irritation test and H&E staining of eye-ball tissues, respectively. RESULTS: The bear bile-loaded in-situ ocular gel showed excellent stability at different pH (pH 5.0, 5.5, 6.0, 6.5, 7.0 and 8.0) up to 5 days, and bear bile extract significantly attenuated the gelling ability of the in-situ gel. The viscosity of in-situ gels formulation was decreased with increase in shear rate (0.01 to 100 s-1), and morphological examination of freeze-dried preparation showed three-dimensional reticular structure at physiological pH. The in-situ ocular gel exhibited promising sustained drug release up to 160 min in vitro, and showed prolonged retention time up to 3-folds in vivo. Finally, the biocompability data confirmed that the formulation did not induce any toxic effects and was completely compatible with eye tissues. CONCLUSION: pH sensitive in-situ ocular gel provides new research opportunities to efficiently treat eye diseases.

Overview of the STAT-3 signaling pathway in cancer and the development of specific inhibitors.

Signal transducer and activator of transcription (STAT) proteins represent novel therapeutic targets for the treatment of cancer. In particular, STAT-3 serves critical roles in several cellular processes, including the cell cycle, cell proliferation, cellular apoptosis and tumorigenesis. Persistent activation of STAT-3 has been reported in a variety of cancer types, and a poor prognosis of cancer may be associated with the phosphorylation level of STAT-3. Furthermore, elevated STAT-3 activity has been demonstrated in a variety of mammalian cancers, both in vitro and in vivo. This indicates that STAT-3 serves an important role in the progression of numerous cancer types. A significant obstacle in developing STAT-3 inhibitors is the demonstration of the antitumor efficacy in in vivo systems and the lack of animal models for human tumors. Therefore, it is crucial to determine whether available STAT-3 inhibitors are suitable for clinical trials. Moreover, further preclinical studies are necessary to focus on the impact of STAT-3 inhibitors on tumor cells. When considering STAT-3 hyper-activation in human cancer, selective targeting to these proteins holds promise for significant advancement in cancer treatment. In the present study, advances in our knowledge of the structure of STAT-3 protein and its regulatory mechanisms are summarized. Moreover, the STAT-3 signaling pathway and its critical role in malignancy are discussed, in addition to the development of STAT-3 inhibitors in various cancer types.

Insight on Multidrug Resistance and Nanomedicine Approaches to Overcome MDR.

Multidrug resistance (MDR) remains a major obstacle to ensure effective chemotherapy in cancer patients. Several factors could be associated with cancer cells' drug resistance such as overexpression of P-glycoprotein (P-gp), cancer stem cells (CSCs), defect in apoptosis, mutation and alteration in DNA repair pathways, angiogenesis, autophagy, and modulation in metabolic enzymes. Until now, drug efflux by ABC transporters has been a univocal and well-established mechanism of chemotherapeutic associated drug resistance. To explore the mechanics involved in ABC transporter associated drug resistance, many crucial studies have been conducted from identification of drug binding sites to elucidation of their structure. Due to our continuous battle with drug resistance, several strategies have been employed to combat MDR, including P-gp modulators, siRNAs, antibodies, as well as peptides. Furthermore, various nanoparticle and different effective combination nanomedicine strategies also suggest some exciting results. Thus, to improve nanomedicine approaches to overcome MDR, in this evolutionary review, we have focused on fundamentals of possible strategies as well as the latest accomplishments to reverse MDR.

Polymeric emulgel carrying Cinnamomum tamala extract: promising delivery system for potential topical applications

Currently, the use of natural compounds obtained from plants tremendously increased due to their promising therapeutic properties. The aim of this study was to formulate a stable emulgel formulation loaded with Cinnamomum tamala (CT) extract. The antioxidant activity of plant extract was determined by DPPH inhibition assay. The extract was successfully loaded into an emulgels using different concentrations of carbopol-940, liquid paraffin, emulsifying agents and preservatives. Preliminary stability study was performed of 17 CT emulgel formulations at accelerated temperature of 50 °C for 2-months. Organoleptic evaluation, centrifugation, globule size, pH, electrical conductivity and rheological studies were performed for a period of 90-days at different temperature including 8, 25, 40 and 40 °C ±75% RH. The CT extract showed promising antioxidant activity of about 81%. On the other hand, the CT loaded emulgel formulation displayed high physical stability at all tested conditions of temperature and time. However, slight decrease in pH and minimum increase in conductivity was observed at 40 and 40 °C±75% RH. The rheological examination of CT emulgel indicated the flow index values of all the samples kept at different temperatures were less than 1, demonstrated non-newtonian and pseudo-plastic nature of CT emulgel. Taken together, the CT emulgel formulation has been evinced to be an excellent addition in the field of topical formulations.

Drug nanocrystals: Fabrication methods and promising therapeutic applications.

The drug nanocrystals (NCs) with unique physicochemical properties are now considered as a promising drug delivery system for poorly water-soluble drugs. So far >20 formulations of NCs have been approved in the market. In this review, we summarized recent advances of NCs with emphasis on their therapeutic applications based on administration route and disease states. At the end, we present a brief description of the future perspectives of NCs and their potential role as a promising drug delivery system. As a strategy for solubilization and bioavailability enhancement, the NCs have gained significant success. Besides this, the function of NCs is still far from developed. The emerging NC-based drug delivery approach would widen the applications of NCs in drug delivery and bio-medical field. Their in vitro and in vivo fate is extremely unclear; and the development of hybrid NCs with environment-sensitive fluorophores may assist to extend the scope of bio-imaging and provide better insight to their intracellular uptake kinetics, in vitro and in vivo.

Drug-delivering-drug approach-based codelivery of paclitaxel and disulfiram for treating multidrug-resistant cancer.

Multidrug resistance (MDR) is a common intractable barrier in success of clinical cancer chemotherapy. Codelivery of two drugs using nanocarriers is a commonly used approach to treat the MDR cancer. However, the drug payload in the conventional nanocarriers is low and thus compromises the treatment outcomes. Disulfiram (DSF) is promising to reverse MDR and increases the sensitivity of cancer cells to chemotherapy. While, paclitaxel (PTX) is one of the frequently used anticancer drug. Here, by using a drug-delivering-drug (DDD) strategy based on nanocrystals, hybrid PTX-DSF nanocrystals (PTX-DSF Ns) were developed for codelivery of PTX and DSF to reverse MDR in cancer. The 160-nm PTX-DSF Ns with rod-like morphology had drug-loading up to 43% at mass ratio of 5:1. Interestingly, the nanoparticles entered cells via caveolar endocytosis. By reducing intracellular ATP level and GST activity, PTX-DSF Ns killed the Taxol resistant A549 cells with higher efficiency than PTX alone, exhibiting as 6-fold increase of apoptosis in MDR tumor. The nanoparticles circulated in blood over time, accumulated in tumor efficiently and reduced the tumor volume by 12-fold in MDR tumor-bearing BALB/c nude mice and allowed 12-fold apoptosis in tumor. Additionally, the immunohistochemical examination demonstrated the safety of the nanoparticles. Overall, the DDD strategy-based PTX-DSF Ns have promising potential for the treatment of MDR cancer.

Molecular Alteration Analysis of Human Gut Microbial Composition in Graves' disease Patients.

The gut microbial association with host co-existence is critical for body homeostasis and pathogenicity. Graves' disease (GD) is an autoimmune disease manifested with hyperthyroidism and ophthalmopathy. However, we hypothesized that gut bacteria could affect an important role in GD pathogenicity. The current study aim was to characterize and investigate the intestinal bacterial composition of GD qualitatively and quantitatively. 27 GD and 11 healthy controls were enrolled for fecal sample collection. The PCR-DGGE of 16S rRNA gene by targeting V3 region and Real-time PCR for Lactobacillus, Bifidobacterium, Bacteroides vulgatus and Clostridium leptum, were performed. High-throughput sequencing of 16S rRNA gene with the V3+V4 site was perormed on Hiseq2500 platform on randomly 20 selected samples. The relative analysis of richness indices and diversity illustrated lesser diversification of intestinal bacteria in GD patients in contrast to controls. The data statistics shows the alteration in phyla of GD as compared to control. At the family taxonomic level, the relative abundance of Prevotellaceae and Pasteurellaceae were significantly higher in patients, while Enterobacteriaceae, Veillonellaceae, and Rikenellaceae were significantly lower in the diseased group as compared to control. At the genus level, a significant raised in genera count of the diseased group were Prevotella_9 and Haemophilus, while significantly decreased in the genera of the GD group were Alistipes and Faecalibacterium. The modulation in intestinal bacterial composition was checked at species level particularly H. parainfluenza abundance was raised in GD. The outcomes of the current study are aligned with the proposed hypothesis of gut microbial dysbiosis in GD. Statistically, alpha indices and differential abundance analyses of each intestinal bacterial community were significantly changed in GD. Therefore, the current study may provide a new insight into the GD pathogenesis and, in turn, explore its contribution in possible treatments.

Phytocosmeceutical formulation development, characterization and its in-vivo investigations.

Several plants found rich in flavonoid, polyphenols, and antioxidants reported antiaging, oppose inflammation and carcinogenic properties but have rarely been applied in dermatology. The present study was an active attempt to formulate a stable phytocosmetic emulsion system loaded with 2% pre-concentrated Prosopis cineraria bark extract, aiming to revive facial skin properties. In order to obtain potent therapeutic activities, we first prepared extracts of stem, leaves, and bark and screen them on basis of phenolic, flavonoids contents and antioxidant, antibacterial, lipoxygenase and tyrosinase inhibition activities. Furthermore, cytocompatibility of the extract was also determined prior starting in vivo investigations. Then the in vivo performance of 2% bark extract loaded emulsion formulation was determined by using non-invasive probe cutometer and elastometer with comparison to base formulation. The preliminary experiment showed that bark extract has a significant amount of phenolic and flavonoid compounds with eminent antioxidant potential. Furthermore, indicated an efficient antibacterial, lipoxygenase, and tyrosinase enzyme inhibition activities. Importantly, the bark extract did not induce any toxicity or apoptosis, when incubated with HaCat cells. Moreover, the in vivo results showed the formulation (size 3 µm) decreased the skin melanin, erythema and sebum contents up to 2.1-,2.7-and 79%, while increased the skin hydration and elasticity up to 2-folds and 22% as compared to the base, respectively. Owing to enhanced therapeutic effects the phytocosmetic formulation proved to be a potential skin whitening, moisturizer, anti-acne, anti-wrinkle, anti-aging therapy and could actively induce skin rejuvenation and resurfacing.

A Smart Paclitaxel-Disulfiram Nanococrystals for Efficient MDR Reversal and Enhanced Apoptosis.

PURPOSE: A multidrug resistance (MDR) modulator, disulfiram (DSF), was incorporated into pure paclitaxel (PTX) nanoparticles to construct a smart paclitaxel-disulfiram nanococrystals (PTX-DSF Ns) stabilized by ß-lactoglobulin (ß-LG), with the aim to reverse MDR and therefore enhnce cytotoxicity towards Taxol-resistant A549 cells (A549/TAX). METHOD: PTX-DSF Ns was prepared by antisolvent precipitation method. Flow cytometry was used to determine the cell uptake, drug efflux inhibition, cell cycle phase arrest and apoptosis. MDR-1 gene expression level was detected by real time quantitative PCR and gel electrophoresis. RESULTS: PTX-DSF Ns prepared from the optimized formulation had an optimum diameter of 160 nm, was stable and had a high drug-loading capacity. Importantly, the uptake of PTX-DSF Ns in A549/TAX cells was 14-fold greater than the uptake of PTX Ns. Furthermore, PTX-DSF Ns promoted 5-folds increase in apoptosis, enabled 7-folds reduction in the IC50, and rendered 8.9-fold decrease in the dose compared with free PTX. CONCLUSION: PTX-DSF Ns with a precise mass ratio offer efficient cytotoxicity against Taxol-resistant cells and a novel approach for codelivery and sensitizing MDR cancer to chemotherapy. In addition, the use of nanosuspensions as a combined treatment provides a new research avenue for nanosuspensions.

Chitooligosaccharide: An evaluation of physicochemical and biological properties with the proposition for determination of thermal degradation products.

Being the most versatile biopolymer, chitooligosaccharide/chitosan oligosaccharide (COS) has been extensively studied for a range of exceptional biological activities and potential developments of novel medical devices and systems in biomedical and pharmaceutical fields. While possessing intrinsic biocompatibility, mucoadhesiveness, and non-toxicity it gained more interests in the biomedical development of novel systems, devices, and pharmaceutical formulations. The bioactive relativity of chitosan and COS are of highly significant and thus explored in this paper while highlighting its multiple biological activities and promising biomedical applications. More emphasis is on the molecular weight, degree of acetylation/deacetylation, degree of polymerization and reactive groups in relation to chitin and chitosan. Despite COS wide acceptance and utilization, the associated viscosity and instability are crucial factors that posed a great challenge to researchers. The apparent reason attributed to instability and viscosity could be the presence intrinsic variable oligomers within COS. Due to lack of data on safety and impurity analysis of thermal exposure of COS, we hypothesized that different molecules could be generated with thermal treatment of COS, thus finally suggested a prospective determination of thermal degradation product(s)in COS. Hence the aim of this paper is to highlight COS physicochemical and biological significance with reference to its recent developments and propose a further chemical analysis thermal treated COS. This could trigger future researchers for possible isolation and characterization of distinct biomolecules from COS.

Understanding of human ATP binding cassette superfamily and novel multidrug resistance modulators to overcome MDR.

Indeed, multi-drug resistance (MDR) is a significant obstacle to effective chemotherapy. The overexpression of ATP-binding cassette (ABC) membrane transporters is a principal cause of enhanced cytotoxic drug efflux and treatment failure in various types of cancers. At cellular level, the pumps of ABC family regulate the transportation of numerous substances including drugs in and out of the cells. In past, the overexpression of ABC pumps suggested a well-known mechanism of drug resistance in cancers as well as infectious diseases. In oncology, the search for new compounds for the inhibition of these hyperactive ABC pumps either genetically or functionally, growing interest to reverse multi-drug resistance and increase chemotherapeutic effects. Several ABC pump inhibitor/modulators has been explored to address the cancer associated MDR. However, the clinical results are still disappointing and conventional chemotherapies are constantly failed in successful eradication of MDR tumors. In this context, the structural and functional understanding of different ATP pumps is most important. In this concise review, we elaborated basic crystal structure of ABC transporter proteins as well as its critical elements such as different domains, motifs as well as some important amino acids which are responsible for ATP binding and drug efflux as well as demonstrated an ATP-switch model employed by various ABC membrane transporters. Furthermore, we briefly summarized different newly identified MDR inhibitors/modulators, deployed alone or in combination with cytotoxic agents to deal with MDR in different types of cancers.

The promising future of ventricular restraint therapy for the management of end-stage heart failure.

Complicated pathophysiological syndrome associated with irregular functioning of the heart leading to insufficient blood supply to the organs is linked to congestive heart failure (CHF) which is the leading cause of death in developed countries. Numerous factors can add to heart failure (HF) pathogenesis, including myocardial infarction (MI), genetic factors, coronary artery disease (CAD), ischemia or hypertension. Presently, most of the therapies against CHF cause modest symptom relief but incapable of giving significant recovery for long-term survival outcomes. Unfortunately, there is no effective treatment of HF except cardiac transplantation but genetic variations, tissue mismatch, differences in certain immune response and socioeconomic crisis are some major concern with cardiac transplantation, suggested an alternate bridge to transplant (BTT) or destination therapies (DT). Ventricular restraint therapy (VRT) is a promising, non-transplant surgical treatment wherein the overall goal is to wrap the dilated heart with prosthetic material to mechanically restrain the heart at end-diastole, stop extra remodeling, and thereby ultimately improve patient symptoms, ventricular function and survival. Ventricular restraint devices (VRDs) are developed to treat end-stage HF and BTT, including the CorCap cardiac support device (CSD) (CSD; Acorn Cardiovascular Inc, St Paul, Minn), Paracor HeartNet (Paracor Medical, Sunnyvale, Calif), QVR (Polyzen Inc, Apex, NC) and ASD (ASD, X. Zhou). An overview of 4 restraint devices, with their precise advantages and disadvantages, will be presented. The accessible peer-reviewed literature summarized with an important considerations on the mechanism of restraint therapy and how this acquaintance can be accustomed to optimize and improve its effectiveness.

A novel ventricular restraint device (ASD) repetitively deliver Salvia miltiorrhiza to epicardium have good curative effects in heart failure management.

A novel ventricular restraint is the non-transplant surgical option for the management of an end-stage dilated heart failure (HF). To expand the therapeutic techniques we design a novel ventricular restraint device (ASD) which has the ability to deliver a therapeutic drug directly to the heart. We deliver a Traditional Chinese Medicine (TCM) Salvia miltiorrhiza (Danshen Zhusheye) through active hydraulic ventricular support drug delivery system (ASD) and we hypothesize that it will show better results in HF management than the restraint device and drug alone. SD rats were selected and divided into five groups (n=6), Normal, HF, HF+SM (IV), HF+ASD, HF+ASD+SM groups respectively. Post myocardial infarction (MI), electrocardiography (ECG) showed abnormal heart function in all groups and HF+ASD+SM group showed a significant therapeutic improvement with respect to other treatment HF, HF+ASD, and HF+SM (IV) groups on day 30. The mechanical functions of the heart such as heart rate, LVEDP, and LVSP were brought to normal when treated with ASD+SM and show significant (P value<0.01) compared to other groups. BNP significantly declines in HF+ASD+SM group animals compared with other treatment groups. Masson's Trichrome staining was used to study histopathology of cardiac myocytes and quantification of fibrosis was assessed. The large blue fibrotic area was observed in HF, HF+ASD, and HF+SM (IV) groups while HF+ASD+SM showed negligible fibrotic myocyte at the end of study period (30days). This study proves that novel ASD device augments the therapeutic effect of the drug and delivers Salvia miltiorrhiza to the cardiomyocytes significantly as well as provides additional support to the dilated ventricle by the heart failure.