Role In Disease Therapy Research Articles

Microneedle and Polymeric Films: Delivery of Proteins, Peptides and Nucleic Acids.

In the last 20years, protein, peptide and nucleic acid-based therapies have become the fastest growing sector in the pharmaceutical industry and play a vital role in disease therapy. However, the intrinsic sensitivity and large molecular sizes of biotherapeutics limit the available routes of administration. Currently, the main administration routes of biomacromolecules, such as parenteral, oral, pulmonary, nasal, rectal and buccal routes, each have their limitations. Several non-invasive strategies have been proposed to overcome these challenges. Researchers were particularly interested in microneedles (MNs) and polymeric films because of their less invasiveness, convenience and greater potential to preserve the bioactivity of biotherapeutics. By facilitating with MNs and polymeric films, biomacromolecules could provide significant benefits to patients suffering from various diseases such as cancer, diabetes, infectious and ocular diseases. However, before these devices can be used on patients, how to upscale MN manufacture in a cost-effective and timely manner, as well as the long-term safety of MN and polymeric film applications necessitates further investigation.

Pumpkin seed proteins (Cucurbita pepo L.) protect against diet-induced metabolic syndrome by improving insulin resistance and markers of oxidative stress and inflammation in rats

Pumpkin (Cucurbita pepo L.) seeds are enriched in bioactive compounds having functional properties. The aim of this study was to analyze the pumpkin seed proteins (PSP) effects on insulin resistance, oxidative stress damage and inflammation in rats with high fructose-induced metabolic syndrome.Twenty four male Wistar rats, fed isoenergetic diets supplemented with: (1) 20% casein (C); (2) 20% casein and 1 g/kg/day PSP (P); (3) 20% casein and 64% D-fructose (C-HF); (4) 20% casein, 1 g/kg/day PSP and 64% D-fructose (P-HF). After 8 weeks of treatment, fructose supply impaired white adipose tissue (WAT) weight, deteriorated glucose tolerance and tAUC, plasma glucose, insulin, insulinogenic index, HOMA-IR and HOMA-β, antioxidant status, lipid and protein oxidation, plasma TNF-α and IL-6 as compared to control diets. Interestingly, rats assigned to the PSPs diet with or without fructose displayed lower plasma glucose, insulin and fructose, improved tolerance of glucose, tAUC, HOMA-IR and HOMA-β and increased insulinogenic index as compared to C diets. PSPs consumption lowered thiobarbituric acid reactive substances, hydroperoxides and carbonyls in WAT and carbonyls in muscle. Superoxide dismutase and glutathione peroxidase in WAT were significantly diminished in P-HF but increased in P as compared to C-HF and C. Rats fed P-HF diet had low catalase in WAT and high in muscle than those fed C-HF. Moreover, catalase activity increased in muscle but decreased in WAT in P group than in C group. In conclusion, pumpkin seed proteins exhibit favorable effects on metabolic disorders of fructose-induced metabolic syndrome, suggesting a key role in disease therapy.

Development of cannabidiol as a treatment for severe childhood epilepsies.

In recent years, there has been a growing appreciation by regulatory authorities that cannabis-based medicines can play a useful role in disease therapy. Although often conflagrated by proponents of recreational use, the legislative rescheduling of cannabis-derived compounds, such as cannabidiol (CBD), has been associated with the steady increase in the pursuit of use of medicinal cannabis. One key driver in this interest has been the scientific demonstration of efficacy and safety of CBD in randomised, placebo-controlled clinical trials in children and young adults with difficult-to-treat epilepsies, which has encouraged increasing numbers of human trials of CBD for other indications and in other populations. The introduction of CBD as the medicine Epidiolex in the United States (in 2018) and as Epidyolex in the European Union (in 2019) as the first cannabis-derived therapeutic for the treatment of seizures was underpinned by preclinical research performed at the University of Reading. This work was awarded the British Pharmacological Society Sir James Black Award for Contributions to Drug Discovery 2019 and is discussed in the following review article.

Clinical features and in vivo confocal microscopy assessment in 12 patients with ocular cicatricial pemphigoid.

To describe the clinical features and microstructural characteristics assessed by in vivo confocal microscopy (IVCM) in patients with ocular cicatricial pemphigoid (OCP). A descriptive, uncontrolled case series study. Patients diagnosed with OCP were examined by clinical history, slit-lamp biomicroscopy features and IVCM images. The results of direct immunofluorescence (DIF) biopsies and indirect immunofluorescence (IIF) were also recorded. Local and systemic immunosuppressive therapy were administered and adjusted according to response. A total of 12 consecutive OCP patients (7 male, 5 female; mean age 60.42±10.39y) were recruited. All patients exhibited bilateralprogressive conjunctival scarring and recurrent chronic conjunctivitis was the most frequent clinical pattern. The mean duration of symptoms prior to diagnosis of OCP was 2.95±2.85y (range: 5mo to 10y). The Foster classification varied from stage I to IV and 20 eyes (83%) were within or greater than Foster stage III on presentation. Two of the 12 patients (17%) demonstrated positive DIF; 3 of the 12 (25%) patients reported positive IIF. The mean duration of the follow-up period was 20.17±11.88mo (range: 6 to 48mo). IVCM showed variable degrees of abnormality in the conjuctiva-cornea and conjuctival scarring was detected in all the involved eyes. Corneal stromal cell activation and dendritic cell infiltration presented as ocular surface inflammation, ocular surface keratinization along with the destroyed Vogt palisades was noted in eyes with potential limbal stem cell deficiency. After treatment, remission of ocular surface inflammation was achieved in all the patients, 18 eyes (75%) remained stable, 6 eyes (25%) had recurrent conjunctivitis and cicatrization in 2 eyes (8%) was progressing. As an autoimmune disease, OCP manifests as variable degrees of clinical and laboratory abnormalities with both local and systemic immunosuppressive treatment playing important roles in disease therapy. IVCM can be as a valuable non-invasive technique to assess ocular surface changes in a cellular level with a potential value for providing diagnostic evidence and monitoring therapeutic effects during follow-up.

Unique Diagnostic and Therapeutic Roles of Porphyrins and Phthalocyanines in Photodynamic Therapy, Imaging and Theranostics

Porphyrinic molecules have a unique theranostic role in disease therapy; they have been used to image, detect and treat different forms of diseased tissue including age-related macular degeneration and a number of different cancer types. Current focus is on the clinical imaging of tumour tissue; targeted delivery of photosensitisers and the potential of photosensitisers in multimodal biomedical theranostic nanoplatforms. The roles of porphyrinic molecules in imaging and pdt, along with research into improving their selective uptake in diseased tissue and their utility in theranostic applications are highlighted in this Review.

Immunomodulatory activities of five clinically used Chinese herbal polysaccharides

Polysaccharide is a natural macromolecular compound with complex, important and multifaceted biological activities. Some of polysaccharides have been marketed in China as drugs or healthy products. More studies confirm that the active ingredient of many traditional Chinese medicine exist in the form of polysaccharides. They play a role in disease therapy by activating immune cells and the complement system; regulating the cytokines expression; promoting the production of antibodies; inhibiting tumor cell proliferation and inducing tumor cell apoptosis; inhibiting virus entering cells and replication; increasing activity of antioxidant enzyme; scavenging free radicals; and inhibiting lipid peroxidation. In this review, we focus on the immunomodulatory effects and its possible mechanism of polysaccharides from Chinese herbal polysaccharides products, including Lentinan, Astragalus polysaccharide, Polyporus polysaccharide and Achyranthes bidentata polysaccharide. The immunomodulatory activities of polysaccharides were categorized in the paper into general immunoregulatory activity, anti-tumor, anti-infections, anti-inflammatory, anti-oxidative, anti-mutagenic and radioprotective, anti-complementary, anti-adhesive, and anti-allergy since all the activities are related to modulate immune responses by the polysaccharides. Also the challenges in the research of polysaccharides will be discussed.