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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

(A) Biopharmaceutical classification system, (B) Features of NCs: increased saturation solubility due to increased dissolution pressure of small nanocrystals (upper), increased dissolution rate due to increased surface area (bottom) and (C) Advantages and disadvantages of NCs associated with different routes of administration. 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. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract 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. [ABSTRACT FROM AUTHOR]

Graphical abstract The w/o emulsion loaded with 2% Prosopis cineraria extract rich in polyphenol, flavonoids and antioxidants was prepared. The polyphenols and flavonoids inhibit tyrosinase and PPAR- γ, which is a key enzyme in melanin synthesis and sebum production, respectively. Whereas, the anti-oxidants suppress the ROS production, proportional to the skin erythema. While, polyphenols and flavonoids have high affinity for skin collagen and elastin fibers that results in increased skin elasticity and moisturization. Highlights • Total phenolic, flavonoid, antioxidant, lipoxygenase, tyrosinase, anti-bacterial activity of stem, leaf and bark extract of Prosopis cineraria. • In-vitro cytocompatibility of bark extract of Prosopis cineraria. • Preparation of stable phytocosmetic emulsion formulation loaded with 2% pre-concentrated Prosopis cineraria bark extract. • In-vitro rheological evaluation of formulation. • Effect on skin melanin, erythema, sebum, hydration & elasticity levels post-treatment with phytocosmetic emulsion formulation. Abstract 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The gut microbiota has a crucial effect on human health and physiology. Hypothyroid Hashimoto’s thyroiditis (HT) is an autoimmune disorder manifested with environmental and genetic factors. However, it is hypothesized that intestinal microbes might play a vital role in the pathogenesis of HT. The aim of current was to investigate and characterize the gut microbial composition of HT patients both quantitatively and qualitatively. The fecal samples from 29 HT patients and 12 healthy individuals were collected. The PCR-DGGE targeted V3 site of 16S rRNA gene and real time PCR for Bifidobacterium Lactobacillus , Bacteroides vulgatus and Clostridium leptum were performed. Pyrosequencing of 16S rRNA gene with V4 location was performed on 20 randomly selected samples. The comparative analysis of diversity and richness indices revealed diversification of gut microbiota in HT as compared to control. The statistical data elucidate the alterations in phyla of HT patients which was also affirmed at the family level. We observed the declined abundance of Prevotella_9 and Dialister, while elevated genera of the diseased group included Escherichia-Shigella and Parasutterella . The alteration in gut microbial configuration was also monitored at the species level, which showed an increased abundance of E. coli in HT. Therefore, the current study is in agreement with the hypothesis that HT patients have intestinal microbial dysbiosis. The taxa statistics at species-level along with each gut microbial community were modified in HT. Thus, the current study may offer the new insights into the treatment of HT patients, disease pathway, and mechanism. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Over the past few years, it was suggested that a rational approach to treat cancer in clinical settings requires a multipronged approach that augments improvement in systemic efficiency along with modification in cellular phenotype leads to more efficient cell death response. Recently, the combinatory delivery of traditional chemotherapeutic drugs with natural compounds proved to be astonishing to deal with a variety of cancers, especially that are resistant to chemotherapeutic drugs. The natural compounds not only synergize the effects of chemotherapeutics but also minimize drug associated systemic toxicity. In this review, our primary focus was on antitumor effects of natural compounds. Previously, the drugs from natural sources are highly precise and safer than drugs of synthetic origins. Many natural compounds exhibit anti-cancer potentials by inducing apoptosis in different tumor models, in-vitro and in-vivo. Furthermore, natural compounds are also found equally useful in chemotherapeutic drug resistant tumors. Moreover, these Phyto-compounds also possess numerous other pharmacological properties such as antifungal, antimicrobial, antiprotozoal, and hepatoprotection. Aglycone solasodine and solanidine derivatives are the utmost important steroidal glycoalkaloids that are present in various Solanum species, are discussed here. These natural compounds are highly cytotoxic against different tumor cell lines. As the molecular weight is concerned; these are smaller molecular weight chemotherapeutic agents that induce cell death response by initiating apoptosis through both extrinsic and intrinsic pathways. [ABSTRACT FROM AUTHOR]

Objective(s): 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. [ABSTRACT FROM AUTHOR]

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 (30 days). 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. [ABSTRACT FROM AUTHOR]

Purpose: To determine the antioxidant activity of Crucus sativus extract and its effect on human skin using a non-invasive probe mexameter. Methods: The antioxidant activity of C. sativus extract was determined using DPPH method. Water in oil (w/o) topical cream of C. sativus extract (3%) was formulated and compared with the base (cream without extract). Both creams (formulation and base) were applied to the cheeks of 10 healthy human volunteers for a period of 8 weeks. Melanin and erythema values of skin were measured with a mexameter. Results: The antioxidant activity of the extract was 81%. Change in the levels of skin melanin and erythema was -24.04 ± 3.23 and -13.57 ± 2.28, respectively, indicating that unlike the base, the formulation containing Crocus sativus extract produced significant (p ≤ 0.05) depigmentation and anti erythemic effect on human skin. Conclusion: Application of the formulation containing 3% C. sativus extract to human skin may be useful in the management of melanoma. However, further studies are still required to ascertain this. [ABSTRACT FROM AUTHOR]