Immunomodulation by xylan and carrageenan-type polysaccharides from red seaweeds: Anti-inflammatory, wound healing, cytoprotective, and anticoagulant activities.

The immunomodulatory properties of the polysaccharides (carrageenan, xylan) from Chondrus crispus (CC), Ahnfeltiopsis devoniensis (AD), Sarcodiotheca gaudichaudii (SG) and Palmaria palmata (PP) algal species were studied. Using RAW264.7 macrophages, we investigated the proliferation and migration capacity of different extracts along with their immunomodulatory activities, including nitric oxide (NO) production, phagocytosis, and secretion of pro-inflammatory cytokines. Polysaccharides from C. crispus and S. gaudichaudii effectively mitigated inflammation and improved scratch-wound healing. Polysaccharide fractions extracted under cold conditions (25 °C), including CC-1A, SG-1A and SG-1B stimulated cell proliferation, while fractions extracted under hot conditions (95 °C), including CC-3A, CC-2B and A. devoniensis (AD-3A), inhibited cell proliferation after 48 h. Furthermore, RAW264.7 cells treated with the fractions CC-3A, AD-1A, and SG-2A significantly reduced LPS-stimulated NO secretion over 24 h. Phagocytosis was significantly improved by treatment with C. crispus (CC-2B, CC-3B) and A. devoniensis (AD-3A) fractions. RAW264.7 cells treated with the CC-2A and SG-1A fractions showed elevated TGF-ß1 expression without affecting TNF-α expression at 24 h. Polysaccharide fractions of A. devoniensis (ι/κ hybrid carrageenan; AD-2A, AD-3A) showed the highest anti-coagulation activity. CC-2A and SG-1A fractions enhanced various bioactivities, suggesting they are candidates for skin-health applications. The carrageenan fractions (CC-3A: λ-, µ-carrageenan, SG-2A: ν-, ι-carrageenan) tested herein showed great potential for developing anti-inflammatory and upscaled skin-health applications.

Knowledge and Awareness of Screening for Prostate Cancer Risk Factors and Symptoms Among the General Population in Tabuk City, Saudi Arabia.

Background Early-stage prostate cancer may not show any signs. Digital rectal examination and the prostate-specific antigen test are frequently used in the screening for prostate cancer. The objective of this research is to assess the knowledge and awareness of screening prostate cancer among males in Tabuk, Saudi Arabia. Methodology A cross-sectional study was performed among Saudi males in Tabuk City. A structured interviewing technique based on a questionnaire was used based on the objectives and research questions. Data were collected by well-trained data collectors from the general population in Tabuk City who were randomly chosen in proportion to the city's population density. A multivariate logistic regression analysis was done to evaluate the variables related to knowledge and awareness in this study. Results This questionnaire was completed by a total of 417 male participants. In the studied group, 86.8% of participants had heard about prostate cancer through friends (59%), TV/radio/newspaper (53.24%), and other health services (41.49%). In addition, around 67.6% of participants knew about the prostate cancer screening test. In addition, 32.4% of participants had no prior knowledge of prostate cancer or a screening test. Conclusions There was a good level of awareness and attitude toward screening methods for prostate cancer (54.7%). Aside from having good knowledge regarding prostate cancer symptoms among males in Tabuk City, all participants with regard to demographic distribution showed a significant level of good knowledge and awareness of screening prostate cancer methods and the necessity of performing regular prostate examinations.

Poly(2-Hydroxyethyl Methacrylate) Hydrogel-Based Microneedles for Metformin Release.

The release of metformin, a drug used in the treatment of cancer and diabetes, from poly(2-hydroxyethyl methacrylate), pHEMA, hydrogel-based microneedle patches is demonstrated in vitro. Tuning the composition of the pHEMA hydrogels enables preparation of robust microneedle patches with mechanical properties such that they would penetrate skin (insertion force of a single microneedle to be ≈40 N). Swelling experiments conducted at 20, 35, and 60 °C show temperature-dependent degrees of swelling and diffusion kinetics. Drug release from the pHEMA hydrogel-based microneedles is fitted to various models (e.g., zero order, first order, second order). Such pHEMA microneedles have potential application for transdermal delivery of metformin for the treatment of aging, cancer, diabetes, etc.

Biochemical Characteristics and Potential Biomedical Applications of Hydrolyzed Carrageenans.

Seaweed contains a variety of bioactive compounds; the most abundant of them are polysaccharides, which have significant biological and chemical importance. Although algal polysaccharides, especially the sulfated polysaccharides, have great potential in the pharmaceutical, medical and cosmeceutical sectors, the large molecular size often limits their industrial applications. The current study aims to determine the bioactivities of degraded red algal polysaccharides by several in vitro experiments. The molecular weight was determined by size-exclusion chromatography (SEC), and the structure was confirmed by FTIR and NMR. In comparison to the original furcellaran, the furcellaran with lower molecular weight had higher OH scavenging activities. The reduction in molecular weight of the sulfated polysaccharides resulted in a significant decrease in anticoagulant activities. Tyrosinase inhibition improved 2.5 times for hydrolyzed furcellaran. The alamarBlue assay was used to determine the effects of different Mw of furcellaran, κ-carrageenan and ι-carrageenan on the cell viability of RAW264.7, HDF and HaCaT cell lines. It was found that hydrolyzed κ-carrageenan and ι-carrageenan enhanced cell proliferation and improved wound healing, whereas hydrolyzed furcellaran did not affect cell proliferation in any of the cell lines. Nitric oxide (NO) production decreased sequentially as the Mw of the polysaccharides decreased, which indicates that hydrolyzed κ-Carrageenan, ι-carrageenan and furcellaran have the potential to treat inflammatory disease. These findings suggested that the bioactivities of polysaccharides were highly dependent on their Mw, and the hydrolyzed carrageenans could be used in new drug development as well as cosmeceutical applications.

A novel therapeutic effect of mannitol-rich extract from the brown seaweed Sargassum ilicifolium using in vitro and in vivo models.

BACKGROUND: Wound healing is an active, complex, integrated series of cellular, physiological, and biochemical changes initiated by the stimulus of injury in a tissue. The present study was performed to investigate the potential wound healing abilities of Sargassum ilicifolium crude extracts (CE) that were characterized by 1H NMR and FTIR Spectrometric measurements. MATERIALS AND METHODS: Seaweed samples were collected from southern coastal sites of Sri Lanka. To determine the cytotoxicity and proliferation of S. ilicifolium CE were used for the MTT and alamarBlue assays respectively. The scratch and exclusion wound models were used to HaCaT and HDF cells to assess the cell proliferation and migration. RAW 264.7 cells (macrophages) were used to evaluate Nitric Oxide (NO) production and phagocytosis activities. Moreover, Fifteen, 8-week-old, female, New Zealand rabbits were selected and divided into five groups: excision skin wounds (10.40 ± 0.60 mm) were induced in groups I, II, and III. Rabbits in groups I and IV were given S. ilicifolium CE (orally, 100 mg/kg day, two weeks), whereas groups II and V were given equal amounts of distilled water. Wound healing properties were measured and wound tissue samples were collated, formalin-fixed, wax-embedded, stained (Hematoxylin and Eosin; Van Gieson) and examined for the healing process. RESULTS: Anti-inflammatory and wound healing activities were observed in RAW 264.7, HDF and HaCaT cells treated with S. ilicifolium aqueous extracts when compared to the control groups. S. ilicifolium extracts concentration 8 - 4 µg/µL, (P<0.05) had remarkable the highest proliferative and migratory effects on RAW 264.7, HDF and HaCaT cells when compared with the control. RAW 264.7 cell proliferation and/or migration were higher in S. ilicifolium extracts (4 µg/µL, 232.8 ± 10.07%) compared with the control (100 %). Scratch wound healing were remarkably enhanced in 24 h, 48 h (P<0.05) when treated with S. ilicifolium on HaCaT cells. Rabbits treated with the CE of S. ilicifolium showed a significantly increased wound healing activities (P<0.05) within three days with a close wound area of 57.21 ± 0.77 % compared with control group (26.63 ± 1.09 %). Histopathology, aspartate aminotransferase and alanine aminotransferase levels evidenced no toxic effects on seaweed treated groups. Histopathological results also revealed that the healing process was significantly faster in the rabbit groups which were as treated with CE of S. ilicifolium orally with the evidence of enhanced early granulation tissue (connective tissue and angiogenesis) and significant epithelization compared to the control. CONCLUSIONS: Cell proliferation and migration are significantly faster when treated with S. ilicifolium aqueous extracts. Moreover, there are no toxic effect of S. ilicifolium aqueous extracts on RAW 264.7, HDF and HaCaT cell lines. In this study, it is revealed that S. ilicifolium has potential remedial agent; D-Mannitol for skin wound healing properties that by promote keratinocyte and fibroblast proliferation and migration. These findings show that S. ilicifolium have promising wound healing properties.

Comparative analysis of proximate compositions, mineral and functional chemical groups of 15 different seaweed species.

Seaweed is a popular edible source and is associated with many foods and pharmaceutical industries around the world. The current research aims to provide information on the chemical composition of 15 seaweed species, consisted of Chlorophyta, Ochrophyta/Phaeophyceae, and Rhodophyta macroalgae, collected from coastal areas of Sri Lanka. Seaweed samples were subjected to the analysis of lipids, proteins, ash and macro, micro, trace and ultra-trace elements. The highest protein content was recorded in the brown algae. Maximum dietary fiber and ash contents were recorded from green algae. The highest predominant fatty acids were observed from green seaweeds (Caulerpa racemosa); however, linoleic acid (C18:2n6) is the dominant fatty acid of all macroalgae. Mineral contents were highest in the red macroalga; however, copper, zinc and magnesium were also comparatively higher in green alga Ulva lactuca. In conclusion, 15 seaweed species belonging to the three different classes of seaweeds are investigated in details to obtain their biochemical, mineral and fatty acid compositions for the synthesis of novel therapeutic agents. In order to explore biorefinery processes for these seaweeds, as well as how they can potentially be cultivated, more extensive studies are required. Studying and determining the nutritional values of seaweeds will be beneficial with the potentials for future industrial uses and research.

Clinico-epidemiology and management of hump-nosed pit viper (Hypnale spp.) bites in dogs.

Human envenoming from the bite of the abundant hump-nosed pit viper (Hypnale spp.) (HNPV) is a frequent occurrence with victims experiencing unpleasant and sometimes life-threatening consequences. Further, clinico-pathology, treatment and management measures in HNPV envenomed dogs are under recognized. Prospective investigations were performed to assess the clinico-pathology and management options for HNPV envenomed dogs brought to the University of Peradeniya's Veterinary Teaching Hospital from January, 2012 to March 2018. We recorded the local and systemic manifestations, hematological and urinary abnormalities of 78 dogs in which HNPV bite had been witnessed by the owner. Mild swelling, extensive swelling, hemorrhagic blistering and hemorrhagic bullae at the site of bite were observed in 59%, 31%, 6% and 4% of the dogs, respectively. Some dogs were subjected to surgical excision of necrotized tissue including limb amputation. We observed the following systemic clinical effects in envenomed dogs: neurotoxicity (13%), acute kidney injury (AKI) (14%) and coagulopathy (16%). All dogs showed leukocytosis with mean white blood cell count of 25.25 × 103/µL. Mild anemia and thrombocytopenia were detected in 29% of the dogs. There was a significant correlation between extent of local tissue injuries with length of hospitalization (LH). The mean time of coagulopathy observed was 21.3 h (IQR: 8-48 h). In coagulopathic dogs, there was a strong correlation between LH and extent of local tissue injury (rs = 0.7751, P < 0.0001); LH and whole blood clotting time(CT) (rs = 1.0, P < 0.0001); PT and aPTT (rs = 0.4712, P < 0.001). LH was significantly correlated with the development of AKI (p = 0.0013). Lack of specific antivenom (AVS) for HNPV envenoming provided an opportunity to study the remaining treatment options. Therefore, the study allowed the identification of local and systemic effects, hematological abnormalities, possible supportive treatments and drawbacks of management measures for envenomed dogs.

In vitro and in vivo evaluation of the wound healing properties and safety assessment of two seaweeds (Sargassum ilicifolium and Ulva lactuca).

Seaweeds have been regarded as a reservoir of biologically active molecules that are important in the pharmaceutical industry. The aim of the present study was to explore the wound healing properties and to assess the safety of the seaweed Sargassum ilicifolium and Ulva lactuca. Enhanced cell proliferation and cell migration activities were observed in L929 cells treated with S. ilicifolium extract compared to U. lactuca extract treated cells and the control group. In-vivo experiments were conducted using five groups (10 in each) of Albino mice (BALB/c). Mice in group I and group II were treated (Orally, 100 mg/kg BW/day) with aqueous extracts of S. ilicifolium and U. lactuca, respectively for 14 days. Treatment group III received a topical application of the aqueous extract of S. ilicifolium (25% w/w) and ointment base (75% w/w) (2 g/kg BW/day, for 14 days). Group IV (Control) received an equal amount of distilled water, orally and mice in group V kept without wounds. The extract from S. ilicifolium showed stronger wound healing properties than the one from Ulva lactuca. Histopathological findings also revealed that the healing process was significantly enhanced in the mice group treated orally with S. ilicifolium aqueous extract. These findings show that S. ilicifolium species possess promising wound healing properties in-vitro and in-vivo.

Preliminary screening of the aqueous extracts of twenty-three different seaweed species in Sri Lanka with in-vitro and in-vivo assays.

BACKGROUND: Seaweeds are an important source of bioactive compounds which are applied in various aspects of medicinal investigations. The present study was conducted to investigate cytoxicity (in-vitro and in-vivo) and wound healing activity of different seaweed species in Sri Lanka. METHODS: Twenty-three seaweed samples, belonging to Phaeophyta (Brown), Chlorophyta (Green) and Rhodophyta (Red) were used for the experiments. Samples were collected from the inter-tidal and the sub-tidal habitats around Sri Lankan coast (Southern, Northern and North-western). Aqueous seaweed extracts were tested for cytotoxic and wound healing activity; in-vitro and in-vivo. To determine toxicity of aqueous seaweed extracts, brine shrimp lethality assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) colorimetric assay on mouse fibroblasts (L929) cell line were performed. Cell migration induction of seaweed extracts was assessed by scratch wound healing assay using L929 cell line. Based on the our previous experiments S.ilicifolium (SW23) was selected for the in vivo study to confirm our hypothesis. Albino mice (BALB/c) were divided into three groups (12 in each) and a circular area (44.07 ± 02.51 mm2) of full skin was excised to create a wound in mice group II and III. Group III received aqueous extract of Sargasum illicifolium (400 mg/kg BW/day for 12 days, orally), Group II received distilled water for 12 days whereas Group I was used as the control group and it was tested without forming wounds and without providing any treatment. Further, the expression level of Tumor Necrosis Factor (TNF-α) and Transforming Growth Factor-ß (TGF-ß) via RT-PCR were measured every three days until the end of the experiment. RESULTS: Phytochemical tests showed positive results to flavonoids in all the selected green seaweeds and alkaloids were observed in red seaweeds. In the toxicity assay, red seaweed, Acanthophora spicifera (SW17) was found to be highly effective on nauplii of brine shrimp (LC50 = 0.072 µg/µl). LC50 value of green seaweed species, Caulerpa racemosa (SW02 and SW08) and Caulerpa sertularioides (SW10) was not found within the tested concentration series. The highest cytotoxic effect on L929 cell line was exhibited by aqueous extracts of red seaweed; Jania adhaereus with 50.70 ± 7.304% cell viability compared with control group. The highest cell migration activity was observed in L929 cell line group treated with extracts of green seaweed namely; Halimeda opuntin (SW07) and extracts of brown seaweed namely; Stoechospermum polypodioides (SW11). Extracts of S. illicifolium (SW23) exhibited a significantly enhanced wound healing activity in mice group III within three days (P < 0.05) with an open wound area of 17.35 ± 1.94 mm2 compared with control group (26.29 ± 2.42 mm2). TGF-ß gene expression peaked on 6th day of post-wound and subsequently decreased on 9th day of post-wound in mice group III. TNF-α expression was suppressed in mice group III whereas it was elevated in group II. TGF-ß expression is enhanced in the treatment group compared to the control group. CONCLUSIONS: Aqueous extracts of selected seaweeds are a significant source of potential compounds with wound healing properties, which might be helpful in the healing of various wounds. This also infers that many species of brown and red seaweeds have the potential of wound healing, specifically, Sargasum illicifolium and Jania adhaereus could be a potential candidate for in-vivo studies related to wound healing and cancer therapy in the near future.

The Work Compatibility Improvement Framework: theory and application of improvement action and intervention strategies.

Challenges facing management of manufacturing firms can be transformed into asset gains by giving careful consideration to the worker-work environment interface. The benefits of a 'healthy' interface may lead to sizable reductions in rising health care costs and retention of highly qualified workers. This paper presents a novel approach for the 'improve' phase of the Work Compatibility Improvement Framework. The work tasks of this research consisted of: (a) fundamentals of cognitive-based improvement action and intervention; (b) design concepts and process of improvement action/intervention generation; (c) assessment model of estimated gains in company's assets; (d) application demonstration in the manufacturing sector. The process of improvement action/intervention generation is described, preceded by a description of the fundamentals of cognitive-based improvement action and intervention and system architecture. This is followed by a documentation of estimated asset gains as a result of the improvement plan. The results showed that expert workers were, on average, 78% in agreement with the algorithm-identified improvement actions. Their knowledge was used to update the recommended actions as well as to detail the multiple strategies required to address the improvement actions. As a result, an integrated improvement plan was developed resulting in estimated asset gains of $1.6 million, which was validated by the general manager. The research reported herein documented the theory and application of the 'improve' phase of the Work Compatibility Improvement Framework. The economic assessment of the suggested improvement is also reported and this has proved to be an important driver to secure the firm collaboration of manufacturing enterprise management. An integrated improvement solution plan backed by a detailed economic assessment of suggested improvements is essential to demonstrate the full potential of workplace micro- and macro-ergonomic interventions.

Determinants of business sustainability: an ergonomics perspective.

There is a need to integrate both macro- and micro-ergonomic approaches for the effective implementation of interventions designed to improve the root causes of problems such as work safety, quality and productivity in the enterprise system. The objective of this study was to explore from an ergonomics perspective the concept of business sustainability through optimising the worker-work environment interface. The specific aims were: (a) to assess the working conditions of a production department work process with the goal to jointly optimise work safety, quality and quantity; (b) to evaluate the enterprise-wide work process at the system level as a social entity in an attempt to trace the root causes of ergonomic issues impacting employees throughout the work process. The Work Compatibility Model was deployed to examine the experiences of workers (that is, effort, perceived risk/benefit, performance and satisfaction/dissatisfaction or psychological impact) and their associations with the complex domains of the work environment (task content, physical and non-physical work environment and conditions for learning/growth/development). This was followed by assessment of the enterprise system through detailed interviews with department managers and lead workers. A system diagnostic instrument was also constructed from information derived from the published literature to evaluate the enterprise system performance. The investigation of the production department indicated that the stress and musculoskeletal pain experienced by workers (particularly on the day shift) were derived from sources elsewhere in the work process. The enterprise system evaluation and detailed interviews allowed the research team to chart the feed-forward and feedback stress propagation loops in the work system. System improvement strategies were extracted on the basis of tacit/explicit knowledge obtained from department managers and lead workers. In certain situations concerning workplace human performance issues, a combined macro-micro ergonomic methodology is essential to solve the productivity, quality and safety issues impacting employees along the trajectory or path of the enterprise-wide work process. In this study, the symptoms associated with human performance issues in one production department work process had root causes originating in the customer service department work process. In fact, the issues found in the customer service department caused performance problems elsewhere in the enterprise-wide work process such as the traffic department. Sustainable enterprise solutions for workplace human performance require the integration of macro- and micro-ergonomic approaches.

The work compatibility improvement framework: an assessment of the worker-work environment interaction in the manufacturing sector.

The manufacturing sector in the US is challenged by high health care costs and shortage of qualified workers, which are largely attributed to the degree of fit between the worker and work environment. In this regard, a healthy worker-work environment interface is a necessary and sufficient condition for the containment of health care costs and the retaining/attraction of highly qualified knowledge workers and should be based on the principles of optimum physical, cognitive and emotional health for the workers. In prior research, the Work Compatibility Improvement Framework (WCIF) was introduced as a vehicle to address these issues and was defined as the identification, improvement and maintenance of the well-being characteristics of the workforce and its interaction with the work environment through the application of engineering, medicine, management and human sciences methodologies, technologies and best practices. This paper advances WCIF by examining its applications in manufacturing with regard to the evaluation of working conditions impacting musculoskeletal/stress outcome measures. A study was conducted in a machining department of a bag packaging manufacturer in the Midwest of the United States. The work tasks were planned and executed with regard to the following aims: (1) to compute work compatibility as a function of work demands and energisers; (2) to establish whether the prevalence of musculoskeletal/stress disorders increases with a decrease in the quality of worker-work environment interface in terms of work compatibility level and other work factors such as shift and job category. A major finding is that a 'poor' work environment (a function of all work domains) results in musculoskeletal/stress disorders that are 105% and 67% higher than those for a 'good' work environment. The evening shift exhibited the poorest compatibility followed by the night shift relative to the day shift. Application of the work compatibility approach demonstrated the detection of non-added value work. It is essential to evaluate the various domains of worker-work environment interface to uncover the root causes that tend to sub-optimise the physical/cognitive/emotional health of the workforce. The WCIF was used to uncover the non-value added effort in the work process. These findings will have major implications for developing and implementing customised design interventions with the aim to maximise the benefit and reduce the cost of employees in a manufacturing enterprise. The study findings suggest that the WCIF should be pursued as a potential strategic tool for optimising human performance in an enterprise to create healthy workplaces.