Colon-Adhering Delivery System with Inflammation Responsiveness for Localized Therapy of Experimental Colitis.

Ulcerative colitis (UC) is a chronic inflammation-related disease that severely affects the colon and rectum regions. A variety of therapy regimens are used for the treatment of UC. Clinically, therapeutic enema is the choice of therapy for UC patients. Irrespective of on-site administration, the major limitation of therapeutic enemas is the dispossession of the medicine followed by low drug availability for the therapeutic action. In our present work, we have developed an enzyme-responsive injectable hydrogel (ER-hydrogel) to overcome the limitations of therapeutic enema. The hydrogels possess two major advantages, which are being exploited for therapeutic drug delivery in UC: prolonged retention and enzyme responsiveness. The former is one of the prominent advantages of hydrogel compared to free drug enema and the latter controls the release of the drug or provides drug release on-demand. The ER-hydrogel was formulated by the heat-cool method and for therapeutic purposes, a corticosteroid drug, budesonide (Bud), was encapsulated into the ER-hydrogel and evaluated for its various physicochemical and therapeutic potentials in dextran sodium sulfate (DSS)-induced UC. In vitro and ex vivo adhesion studies confirm the retention or mucoadhesive nature of the ER-hydrogel, and the upsurge in Bud release from the Bud-loaded ER-hydrogel upon the addition of esterase enzyme confirms the enzyme-mediated drug release from the ER-hydrogel. Moreover, Bud-loaded ER-hydrogel exhibited promising results in alleviating the disease activity index of UC, and restored the length of the colon, which is the main hallmark of UC. In terms of the health of the colon tissue, the Bud-loaded ER-hydrogel restored the colonic tissue damage, as seen in the H&E-stained, AB-NR-stained, and HID-AB-stained colon sections. Finally, the Bud-loaded ER-hydrogel also markedly subsided the IL-1ß, TNF-α, MPO, and nitrite levels in serum and colon tissues. Thus, the fabricated Bud-loaded ER-hydrogel possesses appreciable translational potential due to its ability to significantly ameliorate inflammatory changes compared to naive or water-based therapeutic enema in acute experimental colitis in mice.

A derivation of factors influencing homeopaths to promote quackery in Sindh.

This article provides multifaceted information as well as an assessment of how and why homoeopaths engage in quackery, which is neither safe, effective, or legal. The purpose of this study was to investigate the factors that influence the majority of homeopaths in Sindh to promote quackery through allopathic medical system, which is outside the boundaries of a homeopath's practice license and competency. The study also explains why homeopathy has remained popular in Sindh, Pakistan, despite its limitations and waning popularity in the United States (USA), the United Kingdom (UK), Russia, Australia, Canada, France, Germany, Switzerland, and Spain over the last decade, based on major national clinical research studies claiming that homeopathic medicines are no more effective than a placebo.

Enema based therapy using liposomal formulation of low molecular weight heparin for treatment of active ulcerative colitis: New adjunct therapeutic opportunity.

Ulcerative colitis (UC) is an idiopathic bowel disease involving chronic inflammation and ulcers in colon and implicates severe epithelial damage with disruption in colon homeostasis. Presently existing treatments possess serious concerns like off target effects and adverse reactions, drug inactivation, poor absorption and other complications resulting in poor bioavailability. In context of high risk of thrombotic events in UC patients, heparin can offer appreciable benefits in UC management due to its remarkable anti-coagulating properties, its ability to intervene inflammatory pathways and acceleration of wound healing process. However, oral administration of heparin being impractical due to harsh gastric acidic environment and heparin degradation, conventional heparin administration is done via intravenous route. Present study was designed to formulate, characterize and evaluate sustained release heparin formulation in mice model of experimental colitis. Heparin liposomes (HLp) were formulated by solvent evaporation and extrusion process and possessed hydrodynamic diameter of 242 ± 4.3 nm. Size, shape and surface morphology was confirmed by TEM, SEM and AFM micrographs while encapsulation efficiency and loading of heparin in optimized HLp were 59.61% and 12.27%, respectively. HLp enema administration ameliorated gross disease indices like body weight, colon length, stool consistency, fecal occult blood. Further, anti-inflammatory efficacy of HLp was established in histopathological analysis where HLp appreciably restored protective mucin layer, colon epithelial mucosal histoarchitecture and considerably attenuated mast cell infiltration in colon epithelia. Overall, results of this study indicate that HLp demonstrated an appreciable therapeutic efficacy in experimental colitis and these results are attributed to their ability to suppress inflammation.

Multi-Therapeutic Potential of Naringenin (4',5,7-Trihydroxyflavonone): Experimental Evidence and Mechanisms.

Extensive research has been carried out during the last few decades, providing a detailed account of thousands of discovered phytochemicals and their biological activities that have the potential to be exploited for a wide variety of medicinal purposes. These phytochemicals, which are pharmacologically important for clinical use, primarily consist of polyphenols, followed by terpenoids and alkaloids. There are numerous published reports indicating the primary role of phytochemicals proven to possess therapeutic potential against several diseases. However, not all phytochemicals possess significant medicinal properties, and only some of them exhibit viable biological effects. Naringenin, a flavanone found in citrus fruits, is known to improve immunity, repair DNA damage, and scavenge free radicals. Despite the very low bioavailability of naringenin, it is known to exhibit various promising biological properties of medicinal importance, including anti-inflammatory and antioxidant activities. This review focuses on the various aspects related to naringenin, particularly its physicochemical, pharmacokinetic, and pharmacodynamic properties. Furthermore, various pharmacological activities of naringenin, such as anticancer, antidiabetic, hepatoprotective, neuroprotective, cardioprotective, nephroprotective, and gastroprotective effects, have been discussed along with their mechanisms of action.

Autophagy-Inducing Inhalable Co-crystal Formulation of Niclosamide-Nicotinamide for Lung Cancer Therapy.

Niclosamide (NIC), an anthelminthic drug, is found to be promising in overcoming the problem of various types of drug-resistant cancer. In spite of strong anti-proliferative effect, NIC shows low aqueous solubility, leading to poor bioavailability. To overcome this limitation, and enhance its physicochemical properties and pharmacokinetic profile, we used co-crystallization technique as a promising strategy. In this work, we brought together the crystal and particle engineering at a time using spray drying to enhance physicochemical and aerodynamic properties of co-crystal particle for inhalation purpose. We investigated the formation and evaluation of pharmaceutical co-crystals of niclosamide-nicotinamide (NIC-NCT) prepared by rapid, continuous and scalable spray drying method and compared with conventional solvent evaporation technique. The newly formed co-crystal was evaluated by XRPD, FTIR, Raman spectroscopy and DSC, which showed an indication of formation of H bonds between drug (NIC) and co-former (NCT) as a major binding force in co-crystal development. The particle geometry of co-crystals including spherical shape, size 1-5 µm and aerodynamic properties (ED, 97.1 ± 8.9%; MMAD, 3.61 ± 0.87 µm; FPF, 71.74 ± 6.9% and GSD 1.46) attributes suitable for inhalation. For spray-dried co-crystal systems, an improvement in solubility characteristics (≥ 14.8-fold) was observed, relative to pure drug. To investigate the anti-proliferative activity, NIC-NCT co-crystals were investigated on A549 human lung adenomas cells, which showed a superior cytotoxic activity compared with pure drug. Mechanistically, NIC-NCT co-crystals enhanced autophagic flux in cancer cell which demonstrates autophagy-mediated cell death as shown by confocal microscopy. This technique could help in improving bioavailability of drug, hence reducing the need for high dosages and signifying a novel paradigm for future clinical applications.

Preclinical Evidence for the Pharmacological Actions of Glycyrrhizic Acid: A Comprehensive Review.

Glycyrrhiza glabra L. (Family: Fabaceae) is one of the important traditional medicinal plant used extensively in folk medicine. It is known for its ethnopharmacological value in curing a wide variety of ailments. Glycyrrhizin, an active compound of G. glabra, possesses anti-inflammatory activity due to which it is mostly used in traditional herbal medicine for the treatment and management of chronic diseases. The present review is focused extensively on the pharmacology, pharmacokinetics, toxicology, and potential effects of Glycyrrhizic Acid (GA). A thorough literature survey was conducted to identify various studies that reported on the GA on PubMed, Science Direct and Google Scholar.

Engineering red-emitting multi-functional nanocapsules for magnetic tumour targeting and imaging.

In this work we describe the formulation and characterisation of red-emitting polymeric nanocapsules (NCs) incorporating superparamagnetic iron oxide nanoparticles (SPIONs) for magnetic tumour targeting. The self-fluorescent oligomers were synthesised and chemically conjugated to PLGA which was confirmed by NMR spectroscopy, FT-IR spectroscopy and mass spectrometry. Hydrophobic SPIONs were synthesised through thermal decomposition and their magnetic and heating properties were assessed by SQUID magnetometry and calorimetric measurements, respectively. Magnetic nanocapsules (m-NCs) were prepared by a single emulsification/solvent evaporation method. Their in vitro cytotoxicity was examined in CT26 colon cancer cells. The formulated fluorescent m-NCs showed good stability and biocompatibility both in vitro and in vivo in CT 26 colon cancer models. Following intravenous injection, accumulation of m-NCs in tumours was observed by optical imaging. A higher iron content in the tumours exposed to a magnetic field, compared to the contralateral tumours without magnetic exposure in the same animal, further confirmed the magnetic tumour targeting in vivo. The overall results show that the engineered red-emitting m-NCs have great potential as multifunctional nanocarriers for multi-model bioimaging and magnetic-targeted drug delivery.

Hyperbranched Polymer-Functionalized Magnetic Nanoparticle-Mediated Hyperthermia and Niclosamide Bimodal Therapy of Colorectal Cancer Cells.

Functionalized magnetic nanoparticles (MNPs) have attracted particular interest as potential drug delivery carriers as they offer dual advantage of delivering drugs to the target site complemented with magnetic hyperthermia-mediated therapy. Hyperbranched polymer-functionalized MNPs have the potential to perform a dual role of killing cancer cells by hyperthermia (by magnetite core) with apoptosis (by loaded niclosamide). These are formed by the co-precipitation of iron salts followed by aminocellulose grafting, branch growth, and PEGylation. NP formation was investigated by determining particle size, zeta potential, and microscopic (transmission electron microscopy, field-emission scanning electron microscopy, and atomic force microscopy) studies. Results showed that these nanocarriers were 107 ± 57 nm in size with a zeta potential of -18 mV and exist as NPs. Drug loading and encapsulation efficiency were calculated as 15.28 ± 2.72 and 76.41 ± 1.84%, respectively, using UV-vis spectroscopy. NPs were internalized into HCT116 cells as investigated using confocal microscopy and flow cytometry. Blank NPs at the dose of 200 µg/mL were found to be cytocompatible using hTERT cells and hemocompatible. The cell viability study suggested that niclosamide-loaded functionalized magnetic nanoparticles (NFMNPs) were more effective (7 times) than free niclosamide in killing colon cancer cells. Moreover, NFMNPs induced apoptosis in an immunofluorescence study of cleaved caspase-3. Exposure of NFMNPs to an alternating magnetic field (AMF) resulted in a slight increase in the rate of niclosamide release. AMF exposure drastically reduced cell viability due to dual effects of hyperthermia and niclosamide after treatment with NFMNPs. The potentiation of cell death due to dual effects of hyperthermia and niclosamide was further confirmed by Annexin-V/propidium iodide assay using flow cytometry. The results imply that niclosamide delivery through hyperbranched polymer-functionalized MNPs may serve as an effective strategy for the treatment of colorectal cancer.

A secondary analysis of testosterone and electrically evoked resistance training versus testosterone only (TEREX-SCI) on untrained muscles after spinal cord injury: a pilot randomized clinical trial.

STUDY DESIGN: Secondary analysis of a clinical trial. OBJECTIVES: To perform a secondary analysis on the effects of neuromuscular electrical stimulation resistance training (RT) combined with testosterone replacement therapy (TRT) compared with TRT on the untrained muscles after spinal cord injury (SCI). SETTING: Medical research center. METHODS: Twenty-two men with chronic motor complete SCI were randomized into TRT + RT group (n = 11) or TRT group (n = 11). Both groups received 16 weeks of TRT (2-6 mg/day) via testosterone patches. The TRT + RT group received twice weekly progressive RT of the knee extensor muscles using electrical stimulation and ankle weights. Magnetic resonance images were captured to measure cross-sectional areas (CSAs) of trunk, glutei, and leg muscles. RESULTS: Total and absolute gluteus maximus m. (14%, P = 0.003 and 16%, P = 0.001), gluteus medius m. (10%; P = 0.008 and 14%; P = 0.02), and total glutei m. (8%, P = 0.01 and 11%, P = 0.005) CSAs increased overtime for the TRT + RT group. Mean between-group differences of 2.86 (95% CI: 0.30, 5.4), 1.89 (95% CI: 0.23, 3.58) and 5.27 (95% CI: 0.90, 9.69) cm2 were noted for absolute gluteus maximus, total gluteus medius and total glutei CSAs, respectively (P < 0.05). Trunk muscle CSAs showed a trend towards an interaction between groups. CONCLUSIONS: RT combined with low-dose TRT results in significant hypertrophy compared with TRT only on the adjacent untrained glutei muscles. Trunk muscles may require direct stimulation to evoke hypertrophy. These exploratory findings may be of clinical relevance in the reduction of incidence and severity of pelvic pressure injuries.

Thymoquinone (2-Isoprpyl-5-methyl-1, 4-benzoquinone) as a chemopreventive/anticancer agent: Chemistry and biological effects.

Cancer remains the topmost disorders of the mankind and number of cases is unceasingly growing at unprecedented rates. Although the synthetic anti-cancer compounds still hold the largest market in the modern treatment of cancer, natural agents have always been tried and tested for potential anti-cancer properties. Thymoquinone (TQ), a monoterpene and main ingredient in the essential oil of Nigella sativa L. has got very eminent rankings in the traditional systems of medicine for its anti-cancer pharmacological properties. In this review we summarized the diverse aspects of TQ including its chemistry, biosynthesis, sources and pharmacological properties with a major concern being attributed to its anti-cancer efficacies. The role of TQ in different aspects involved in the pathogenesis of cancer like inflammation, angiogenesis, apoptosis, cell cycle regulation, proliferation, invasion and migration have been described. The mechanism of action of TQ in different cancer types has been briefly accounted. Other safety and toxicological aspects and some combination therapies involving TQ have also been touched. A detailed literature search was carried out using various online search engines like google scholar and pubmed regarding the available research and review accounts on thymoquinone upto may 2019. All the articles reporting significant addition to the activities of thymoquinone were selected. Additional information was acquired from ethno botanical literature focusing on thymoquinone. The compound has been the centre of attention for a long time period and researched regularly in quite considerable numbers for its various physicochemical, medicinal, biological and pharmacological perspectives. Thymoquinone is studied for various chemical and pharmacological activities and demonstrated promising anti-cancer potential. The reviewed reports confirmed the strong anti-cancer efficacy of thymoquinone. Further in-vitro and in-vivo research is strongly warranted regarding the complete exploration of thymoquinone in ethnopharmacological context.

Skeletal muscle hypertrophy and attenuation of cardio-metabolic risk factors (SHARC) using functional electrical stimulation-lower extremity cycling in persons with spinal cord injury: study protocol for a randomized clinical trial.

BACKGROUND: Persons with spinal cord injury (SCI) are at heightened risks of developing unfavorable cardiometabolic consequences due to physical inactivity. Functional electrical stimulation (FES) and surface neuromuscular electrical stimulation (NMES)-resistance training (RT) have emerged as effective rehabilitation methods that can exercise muscles below the level of injury and attenuate cardio-metabolic risk factors. Our aims are to determine the impact of 12 weeks of NMES + 12 weeks of FES-lower extremity cycling (LEC) compared to 12 weeks of passive movement + 12 weeks of FES-LEC on: (1) oxygen uptake (VO2), insulin sensitivity, and glucose disposal in adults with SCI; (2) skeletal muscle size, intramuscular fat (IMF), and visceral adipose tissue (VAT); and (3) protein expression of energy metabolism, protein molecules involved in insulin signaling, muscle hypertrophy, and oxygen uptake and electron transport chain (ETC) activities. METHODS/DESIGN: Forty-eight persons aged 18-65 years with chronic (> 1 year) SCI/D (AIS A-C) at the C5-L2 levels, equally sub-grouped by cervical or sub-cervical injury levels and time since injury, will be randomized into either the NMES + FES group or Passive + FES (control group). The NMES + FES group will undergo 12 weeks of evoked RT using twice-weekly NMES and ankle weights followed by twice-weekly progressive FES-LEC for an additional 12 weeks. The control group will undergo 12 weeks of passive movement followed by 12 weeks of progressive FES-LEC. Measurements will be performed at baseline (B; week 0), post-intervention 1 (P1; week 13), and post-intervention 2 (P2; week 25), and will include: VO2 measurements, insulin sensitivity, and glucose effectiveness using intravenous glucose tolerance test; magnetic resonance imaging to measure muscle, IMF, and VAT areas; muscle biopsy to measure protein expression and intracellular signaling; and mitochondrial ETC function. DISCUSSION: Training through NMES + RT may evoke muscle hypertrophy and positively impact oxygen uptake, insulin sensitivity, and glucose effectiveness. This may result in beneficial outcomes on metabolic activity, body composition profile, mitochondrial ETC, and intracellular signaling related to insulin action and muscle hypertrophy. In the future, NMES-RT may be added to FES-LEC to improve the workloads achieved in the rehabilitation of persons with SCI and further decrease muscle wasting and cardio-metabolic risks. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02660073 . Registered on 21 Jan 2016.

Healthcare needs of the Muslim patient community in the undergraduate medical curriculum - Are we there?

OBJECTIVE: Muslim patients have a unique set of healthcare needs that are related to their faith. These are generally not formally addressed in the medical curricula. The study aimed to recommend additional content that would better tailor the undergraduate curriculum to cater to the needs of this large cohort - Muslim patients. This is with the expectation that patients would have their faith-related health queries resolved by healthcare providers. METHODS: A quantitative descriptive survey design was adopted. A 46-item questionnaire formulated through a literature review was put forth to experts using the Delphi Technique. Experts were selected based on having an academic rank of associate professor and above or medical education credentials. Three iterative rounds were conducted for exploring consensus over a period of five months. Panel agreement of >70% was the criteria for inclusion. RESULTS: Items were categorized under 7 subject themes: Medicine, Psychiatry, Surgery, Gynecology, Obstetrics, Medical Ethics, and Islamic Studies. Consensus was eventually reached for 41 out of 46 items. These topics included but were not limited to "The Muslim patient in Ramadan to: fast or not to fast?" and "Muslim women and decision-making on pregnancy termination". CONCLUSION: The study suggested that the topics proposed herein were in fact legitimate faith-related healthcare needs of Muslim patients. Their inclusion would add value to the undergraduate medical curriculum and would train practitioners to improve patient outcomes more holistically.

Osteointegrative and microgeometric comparison between micro-blasted and alumina blasting/acid etching on grade II and V titanium alloys (Ti-6Al-4V).

This study evaluated the effect of alumina-blasted/acid-etched (AB/AE) or microabrasive blasting (C3-Microblasted) surface treatment on the osseointegration of commercially-pure Ti (grade II) and Ti-6Al-4V alloy (grade V) implants compared to as-machined surfaces. Surface characterization was performed by scanning electron microscopy and optical interferometry (IFM) to determine roughness parameters (Sa and Sq, n = 3 per group). One-hundred forty-four implants were placed in the radii of 12 beagle dogs, for histological (n = 72, bone-to-implant contact - BIC and bone-area-fraction occupancy -BAFO) and torque to interface failure test at 3 and 6 weeks (n = 72). SEM and IFM revealed a significant increase in surface texture for AB/AE and C3-Microblasted surfaces compared to machined surface, regardless of titanium substrate. Torque-to-interface failure test showed significant increase in values from as-machined to AB/AE and to C3-Microblasted. Considering time in vivo, alloy grade, and surface treatment, the C3-microblasted presented higher mean BIC values relative to AB/AE and machined surfaces for both alloy types. BAFO levels were significantly higher for both textured surfaces groups relative to the machined group at 3 weeks, but differences were not significant between the three surfaces for each alloy type at 6 weeks. Surface treatment resulted in roughness that improved osseointegration in Grade II and V titanium substrates.

Water-dispersible glycosylated poly(2,5'-thienylene)porphyrin-based nanoparticles for antibacterial photodynamic therapy.

Here we report the preparation of water-dispersible glycosylated poly(2,5'-thienylene)porphyrin based nanoparticles by a nanoprecipitation method and demonstrate the application of these nanoparticles in antibacterial photodynamic therapy. The diameter of the nanoparticles is in the range of 50-80 nm and the resulting nanoparticles are stable in water without precipitation at least for a month. They have high singlet oxygen efficiency and display light-triggered biocidal activity against both Gram negative bacteria (Escherichia coli, E. coli) and Gram positive bacteria (Bacillus subtilis, B. subtilis). Upon white light irradiation for 10 min with a flux of 22 mW cm-2 of the E. coli suspension incubated with NPs (18 µg mL-1), a killing efficiency of 99% is achieved, whereas in the dark the effect is recorded as only around 8%.

Zinc Gluconate-Loaded Chitosan Nanoparticles Reduce Severity of Collagen-Induced Arthritis in Wistar Rats.

Rheumatoid arthritis (RA) is the most prevalent autoimmune disease affecting about 1% world population. Zinc (Zn) is necessary for the maintenance of bone homeostasis and the level of Zn was reported to be decreased in RA patients and collagen-induced arthritic rats. Effective delivery of Zn has been reported using zinc gluconate but oral absorption of Zn from zinc gluconate (ZG) is very low in humans. Zn supplementation reduces disease severity in patients suffering from chronic, refractory RA and exerts mild and transient side effects. The aim of this study was to synthesize and characterize zinc gluconate-loaded chitosan nanoparticles (ZG-Chit NPs) and to evaluate and compare therapeutic efficacy of ZG-Chit NPs and zinc gluconate against collagen-induced RA in Wistar rats. The nanoparticles were formulated by ionic gelation method and the hydrodynamic diameter was 106.5 ± 79.55 nm as measured using DLS. The particle size, shape, and surface morphology was further confirmed by transmission electron microscopy, scanning electron microscopy, and atomic force microscopy. These nanoparticles showed good cytocompatibility against foreskin fibroblasts (BJ) and L929 cells. Arthritic rats were treated with ZG (20 mg/kg body weight, intraperitoneally) and equivalent doses of ZG-Chit NPs. The treatment of both ZG and ZG-Chit NPs reduced the severity of arthritis as evidenced by reduced joint swelling, erythema, and edema but ZG-Chit NPs exhibited superior efficacy. Furthermore, it was found that ZG and ZG-Chit NPs attenuate biomarkers of inflammation (C-reactive protein, myeloperoxidase, nitric oxide, TNF-α, and IL-1ß) and oxidative stress (articular elastase, lipid peroxidation, catalase, glutathione, and superoxide dismutase). The results of the histopathology further confirmed that ZG-Chit NPs markedly suppressed infiltration of inflammatory cells as compared to ZG at the ankle joint tissue. Immunohistochemical analysis also revealed that treatment with ZG-Chit NPs resulted in reduced pro-inflammatory marker (TNF-α, IL-6, and iNOS) expression and enhanced SOD1 expression. Overall, this study suggests that ZG and ZG-Chit NPs suppressed the severity of arthritis plausibly mediated by attenuation of inflammation and oxidative stress and more importantly ZG-Chit NPs exhibited superior efficacy as compared to ZG.

Glycyrrhizic acid suppresses 1,2-dimethylhydrazine-induced colon tumorigenesis in Wistar rats: Alleviation of inflammatory, proliferation, angiogenic, and apoptotic markers.

OBJECTIVES: Colon cancer is the major health disease related with high mortality. Glycyrrhizic acid (GA) is an active constituent of licorice with anti-inflammatory and anticarcinogenesis effects. We investigated the chemopreventive potential of GA against 1,2-dimethylhydrazine (DMH)-induced colon tumorigenesis in Wistar rats. METHODS: Glycyrrhizic acid was administered orally at the dose of 15 mg/kg b.wt. and DMH was administered at the dose of 20 mg/kg b.wt. once a week for first 15 weeks. All the rats were euthanized after 30 weeks. GA supplementation significantly inhibited the tumor incidence and multiplicity. RESULTS: Glycyrrhizic acid treatment reduced the expression of Ki-67, proliferating cell nuclear antigen (PCNA), nuclear factor-kappa B (NF-kB), cyclooxygenase-2 (COX-2), induced nitric oxide synthase (iNOS), and vascular endothelial growth factor (VEGF) while enhanced the expression of p53, connexin-43, b-cell lymphoma-2 (Bcl-2), survivin, and cleaved caspase-3. Glycyrrhizic acid also significantly ameliorated DMH-induced decreased activities of caspase-9 and caspase-3. Furthermore, GA treatment reduced mast cells infiltration, attenuated the shifting of sialomucin to sulphomucin as well the levels of pro-inflammatory cytokines. CONCLUSION: The findings of the study suggest that GA has chemopreventive potential against DMH-induced colon tumorigenesis plausibly through the attenuation of hyperproliferative responses, pro-inflammatory cytokines level, inflammatory and angiogenic markers, and apoptotic responses.

A randomized controlled trial of intermittent Cervical Traction in sitting Vs. Supine position for the management of Cervical Radiculopathy.

OBJECTIVE: To compare the effectiveness of intermittent cervical Traction in sitting vs. supine position for the management of cervical radiculopathy. METHODS: A randomized clinical trial was done to compare pain and disability modification of cervical radiculopathy patients by using cervical traction in sitting and supine positions. Forty patients (males and females aged between 18-60 years with chronic cervical radiculopathy) were recruited for the trial. Participants were randomized into two homogeneous groups by dice method. The Group-A (n=20) received 3-weeks of intermittent cervical traction in sitting position along with Transcutaneous Electric Nerve Stimulation (TENS) and hot pack. The Group-B (n=20) received the same treatment except the intermittent cervical traction that was applied in supine position. Participants were assessed two times: at baseline (week 0) and at the termination of rehabilitation (week 3). Neck disability index was used to collect the data before and after the treatment. RESULTS: The mean age of the patients was 43.15±8.99 vs. 48.80±6.89 years in Group-A vs. Group-B respectively. Mean (±S.D.) weight of the patients was 74.75±12.11 vs. 74.60±11.24 kg in Group-A vs. Group-B respectively. Mean Neck Disability Index score at start of treatment was 30.30±7.46 vs. 30.75±7.85 in Group-A and Group-B respectively. There was a significant difference in Group-A and Group-B regarding aggregate NDI score at the end of treatment (19.45±7.12 vs. 11.05±4.40; p<0.0001). CONCLUSION: Supine position is better choice for applying cervical traction as compared to sitting position for the management of cervical radiculopathy comparing post interventional NDI score.

Suppression of inflammatory response by chrysin, a flavone isolated from Potentilla evestita Th. Wolf. In silico predictive study on its mechanistic effect.

Flavonoids are the most abundant natural polyphenols widely distributed in plants. Among them, chrysin has recently attracted the attention for its anti-tumor and anti-oxidant activities and also for its protective effects on allergic inflammation. Therefore, in this study, we set out to investigate and characterize the effects of chrysin in classical models of inflammation reasoning that this would expand our knowledge on the pharmacological properties of this flavone. To this aim we have firstly isolated chrysin from Potentilla evestita Th. Wolf. and successively evaluated its anti-inflammatory and analgesic potential on writhing and formalin test and also on carrageenan-induced paw oedema. Finally, the present study was planned to investigate, by the aim of docking analysis, the molecular interaction of this compound on the binding site of COX-1 and COX-2 enzymes. On writhing test, we observed a significant inhibition of writhings after the administration of chrysin at 5.0 and 10.0 mg/kg i.p. (25.00±9.22% and 55.67±7.62% respectively). On formalin test, the flavone at dose of 10.0 mg/kg i.p. displayed its maximum analgesic and anti-inflammatory effect on both early (35.67±7.88%) and late phase (50.57±5.36%) and similarly displayed at 4h a significant anti-inflammatory effect in carrageenan-induced paw oedema. Moreover, in silico analysis of receptor ligand complex shows that chrysin interacts weakly with COX-1 binding site whereas displayed a remarkable interaction with COX-2. These findings suggest that the flavone chrysin isolated from P. evestita Th. Wolf. possesses in vivo anti-inflammatory and anti-nociceptive potential, which are supported in silico by an interaction with COX-2 binding site.

Cytotoxic, antitumour-promoting and inhibition of protein denaturation effects of flavonoids, isolated from Potentilla evestita Th. Wolf.

This study was designed to evaluate the isolated flavonoids (chrysin 1, and umbelliferone 2) from Potentilla evestita for cytotoxic, antitumour-promoting and inhibition of protein denaturation activities. The results showed marked cytotoxic effect of compounds 1 and 2 in brine shrimp cytotoxic assay at various concentrations with LD50 of 34.5 and 31.8 mg/mL, respectively. In Epstein-Barr-virus early antigen activation assay, both compounds 1 and 2 illustrated significant antitumour-promoting effect with IC50 values of 462 and 308 mol ratio/32 pmol TPA, respectively. The cytotoxic and antitumour-promoting effects of compounds were strongly supported by inhibition of protein denaturation activity with IC50 of 119 and 112 µg/mL, respectively. In conclusion, both compounds possess strong cytotoxic, antitumour-promoting and inhibition of protein denaturation activities.