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Currently, studies conducted on animal models provide new insight into the aetiology and course of various pathological conditions in humans. Due to the cause of disease, animal models can be divided into two categories: natural models, such as nude mice, and induced models, such as transgenic pigs. This article discusses several examples of animal models and their contributions to the development of effective therapies for human diseases such as muscular dystrophy, cystic fibrosis, and atherosclerosis. In addition, we presented the latest news on gene therapy, xenotransplantation, and drug trials in humans and animals. [ABSTRACT FROM AUTHOR]

Background and objectives: Although the goal of translational research is to bring biomedical knowledge from the laboratory to clinical trial and therapeutic products for improving health, this goal has not been well achieved as often as desired because of many barriers documented in different countries. Therefore, the aim of this study was to investigate the challenges and opportunities of translating animal research into human trials in Ethiopia. Methods: A descriptive qualitative study, using in-depth interviews, was conducted in which preclinical and clinical trial researchers who have been involved in animal research or clinical trials as principal investigator were involved. Data were analyzed using inductive thematic process. Results: Six themes were emerged for challenges: lack of financial and human capacity, inadequate infrastructure, operational obstacles and poor research governance, lack of collaboration, lack of reproducibility of results and prolonged ethical and regulatory approval processes. Furthermore, three themes were synthesized for opportunities: growing infrastructure and resources, improved human capacity and better administrative processes and initiatives for collaboration. Conclusion and recommendations: The study found that the identified characteristics/features are of high importance either to hurdle or enable the practice of translating animal research into human trials. The study suggests that there should be adequate infrastructure and finance, human capacity building, good research governance, improved ethical and regulatory approval process, multidisciplinary collaboration, and incentives and recognition for researchers to overcome the identified challenges and allow translating of animal research into human trials to proceed more efficiently. [ABSTRACT FROM AUTHOR]

AbstractCardiovascular diseases are a major global cause of death and healthcare costs, emphasizing the need for effective prevention and management of cardiometabolic risk factors. One promising approach is the consumption of technologically processed functional foods enriched/fortified with (poly)phenols. The current systematic review aimed to evaluate the human clinical trials evidence on the effect of intake of these foods on reducing the most common cardiometabolic risk factors. 12 randomized controlled studies were included in the systematic review, with varying food intake amounts (27–360 g/day) and (poly)phenol doses (32.5–850 mg/day). These interventions included consumption of functional bakery goods, cereal bars, pasta, chocolate, and yogurt, with supplementation periods spanning from 2 to 52 wk. Several foods, such as green tea extract-fortified rye bread and olive fruit (poly)phenol-fortified yogurt, significantly lowered blood pressure. Flavonoid-enriched chocolate, hydroxytyrosol-fortified bread, and other products influenced glucose metabolism. Additionally, various functional foods were associated with improved blood lipid levels. While these results indicate the health advantages of consuming technologically processed functional foods enriched/fortified with (poly)phenols, caution is warranted due to the scarcity and limitations of existing studies. Further research is needed to confirm and expand upon these results in the prevention and management of cardiometabolic risk factors. [ABSTRACT FROM AUTHOR]

The main aim of this study is to validate the Joint system thermoregulation model (JOS-3 model) for the male population living in tropical climates and to analyze the effect of environmental conditions and physical activities on human thermal comfort. For this, a MATLAB code of the JOS-3 thermoregulation model was developed and verified with experimental data available in the literature. Further, the human trials were conducted in the study under three different scenarios with Indian participants to check the validity of the JOS-3 model for the population living in tropical climates. It was observed that the JOS-3 model could appropriately predict the physiological responses of people living in tropical climates. Additionally, findings from the parametric study show that the mean skin and core temperatures increase as the ambient temperature, relative humidity (RH), and physical activity increase. Besides, the skin temperature is most affected by the ambient temperature, followed by physical activity and RH. On the other hand, the core temperature is most affected by physical activity, followed by the ambient temperature and RH. When physical activity increased from 1.2 to 3.8 MET, mean skin and core temperatures increased by 6.6% and 4.5%, respectively, after 60 min at 38°C, 70% RH, and 0.31 clo. [ABSTRACT FROM AUTHOR]

The use of nanotechnology has the potential to revolutionize the detection and treatment of cancer. Developments in protein engineering and materials science have led to the emergence of new nanoscale targeting techniques, which offer renewed hope for cancer patients. While several nanocarriers for medicinal purposes have been approved for human trials, only a few have been authorized for clinical use in targeting cancer cells. In this review, we analyze some of the authorized formulations and discuss the challenges of translating findings from the lab to the clinic. This study highlights the various nanocarriers and compounds that can be used for selective tumor targeting and the inherent difficulties in cancer therapy. Nanotechnology provides a promising platform for improving cancer detection and treatment in the future, but further research is needed to overcome the current limitations in clinical translation. [ABSTRACT FROM AUTHOR]

Valvular heart disease is a common disease often necessitating valve replacement. Mechanical heart valves (MHVs) are often used in younger patients because of their longer durability. Their main disadvantage is the need for lifelong anticoagulation. Warfarin is considered a standard treatment, but it is far from perfect. Direct oral anticoagulants (DOACs) are a new and more patient-friendly alternative to warfarin when anticoagulation is required, but have not yet been approved for the indication of mechanical valves. Evidence acquisition: A literature search of Pubmed, Embase, Web of Science (Core Collection), and Cochrane Library (from inception to May 2023) was performed using a search string that was well defined and not modified during the study. An extensive overview of the search terms used in each database can be found in the Appendix. Only prospective clinical trials were included in this review. A total of 10 publications were included in this review. Relevance to clinical practice: This systematic review summarizes the different types of DOACs and their possible use in the anticoagulation of mechanical valves. We aim to propose future directions in anticoagulation research for mechanical valves. Conclusions: DOAC use in MHVs has been halted due to the failure of both dabigatran and apixaban in two major clinical trials. However, rivaroxaban was successful in two small clinical trials. Ample research is still needed to explore new valve designs as well as new anticoagulation targets. [ABSTRACT FROM AUTHOR]

Cohorts of healthy younger adults (18–50yrs) and healthy older adults (60–75yrs) were immunized intramuscularly or intranasally with an adenovirus-vectored RSV vaccine (PanAd3-RSV) as a prime dose and boosted with PanAd3-RSV or a poxvirus-vectored vaccine (MVA-RSV) encoding the same insert. Whole blood gene expression was measured at baseline, 3- and 7-days post vaccination. Intramuscular prime vaccination with PanAd3-RSV induced differential expression of 643 genes (DEGs, FDR < 0.05). Intranasal prime vaccination with PanAd3-RSV did not induce any differentially expressed genes (DEGs) in blood samples at 3 days post vaccination. Intranasally primed participants showed greater numbers of DEGS on boosting than intramuscularly primed participants. The most highly enriched biological processes related to DEGs after both prime and boost vaccination were type-1 interferon related pathways, lymphocytic and humoral immune responses. [ABSTRACT FROM AUTHOR]

The hypothalamic–pituitary–adrenal (HPA) axis plays a central role in the stress response. Plants, herbs, spices, and plant-based nutrients may influence HPA-axis activity. To evaluate randomised controlled, human trials assessing the effects of single plants or phytonutrients on HPA-axis related hormones. A systematic review of PubMed, Cochrane library, and the Cumulative Index to Nursing and Allied Health Literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria comprised of human, randomised controlled studies with a control intervention examining the effects of a single herb, spice, plant, or extract on pre- and post-changes in blood, saliva, urine, or hair concentrations of cortisol, cortisone, corticotrophin-releasing hormone, or adrenocorticotropic hormone. Databases were searched from inception until October 2020. Fifty-two studies were identified examining the effects of ashwagandha, Korean ginseng, St John's Wort, cannabidiol, Rhodiola rosea, curcumin, cherry juice, asparagus, Jiaogulan, Black cohosh, Siberian ginseng, Bacopa monnieri, blueberries, green tea, Caralluma fimbriata, cashew apple juice, melon, American ginseng, Ginkgo biloba, grape juice, grapefruit juice, rosella, hops, mangosteen, holy basil, and pomegranate juice. Due to significant variability in study designs, the effect of phytonutrients on HPA-axis activity in humans was unclear. The most consistent finding was a morning, cortisol-lowering effect from ashwagandha supplementation. For most phytonutrients, the effects of supplementation on HPA-axis activity in humans is unclear. Before more definitive conclusions about the effects of phytonutrients on the HPA-axis can be made, further research is required. [ABSTRACT FROM AUTHOR]

We conducted a phase I-IIa, randomized, monocentric, double-blind, placebo-controlled clinical trial to evaluate the safety and impact of the combination treatment of Itolizumab and insulin on preserving beta cell function in adults with recent-onset type 1 diabetes. Twelve patients were randomly assigned to three treatment groups, each receiving a different Itolizumab dose (0.4/0.8/1.6 mg/kg body weight, respectively) and a placebo group. All patients received concomitant intensive multiple-dose insulin therapy. Endogenous insulin secretion was assessed by the measurement of C-peptide during the mixed-meal tolerance test. No serious adverse events were reported. No changes in the total daily insulin doses, glycated hemoglobin levels, and stimulated C-peptide were observed between the Itolizumab and placebo groups at 52 weeks. A significant decrease in stimulated C-peptide was observed during the follow-up period (p = 0.012). One subject treated with 1.6 mg of Itolizumab showed a marked increase in the levels of stimulated C-peptide three years after completion of the trial. Taken together, this is the first study to demonstrate that combination treatment with Itolizumab and insulin is safe in humans and does not affect the residual function of beta cells up to 52 weeks. The findings from our study show preliminary evidence that high doses of Itolizumab could potentially arrest the loss of beta cell function in the long term. Further studies with a longer follow-up and larger numbers of patients are envisaged to assess the effect with high dose Itolizumab. [ABSTRACT FROM AUTHOR]

Cerebrovascular diseases are the second leading cause of death worldwide. Despite significant research investment, the only available therapeutic options are mechanical thrombectomy and tissue plasminogen activator thrombolysis. None of the more than a thousand drugs tested on animal models have proven successful in human clinical trials. Several factors contribute to this poor translation of data from stroke-related animal models to human stroke patients. Firstly, our understanding of the molecular and cellular processes involved in recovering from an ischemic stroke is severely limited. Secondly, although the risk of stroke is particularly high among older patients with comorbidities, most drugs are tested on young, healthy animals in controlled laboratory conditions. Furthermore, in animal models, the tracking of post-stroke recovery typically spans only 3 to 28 days, with occasional extensions to 60 days, whereas human stroke recovery is a more extended and complex process. Thirdly, young animal models often exhibit a considerably higher rate of spontaneous recovery compared to humans following a stroke. Fourth, only a very limited number of animals are utilized for each condition, including control groups. Another contributing factor to the much smaller beneficial effects in humans is that positive outcomes from numerous animal studies are more readily accepted than results reported in human trials that do not show a clear benefit to the patient. Useful recommendations for conducting experiments in animal models, with increased chances of translatability to humans, have been issued by both the STEPS investigative team and the STAIR committee. However, largely, due to economic factors, these recommendations are largely ignored. Furthermore, one might attribute the overall failures in predicting and subsequently developing effective acute stroke therapies beyond thrombolysis to potential design deficiencies in clinical trials. [ABSTRACT FROM AUTHOR]

Edible flowers have been used for their therapeutic properties for ancient times. Many sources indicate, that edible flowers have many beneficial activities like anti-anxiety, anti-cancer, anti-diabetic, anti-inflammatory, antioxidant, diuretic, anthelmintic, immunomodulatory and anti-microbial. People use it also in culinary applications, because they improve the aesthetic value, taste, flavour and appearance of dishes. This study expands knowledge on the content and composition of low molecular phytochemicals of edible flowers and the pro-healthy activities of their extracts or preparations. It is focused on showing flowers which are the best sources of individual compounds and on recent findings with the use of flower extracts or preparations in various cell-lines, animal and human models. Performed comparison of composition includes simple phenolic acids, flavonols, flavanols, flavons, anthocyanidins, carotenoids and tocols. Species with the highest content of selected compounds are highlighted. Unique components of some flowers such as crocin, nimbolide, oleanic and ursolic acids, and acteoside are also mentioned. The potential activity of edible flowers for human health was analysed based on in vitro models with the use of various cell-lines and in vivo models with animal (mostly mice and rat) and human trials. The majority of the reviewed studies confirm the pro-healthy activity of edible flowers or their extracts. Image 1 • Edible flowers are valuable and rich source of many phytochemicals. • Flowers unique compounds are nimbolide, crocin, acteoside, oleanic and ursolic acids. • Flower extracts show a wide array of health promoting properties in vivo. • Crocin have efficiency in treatment people with depression. • Further attention towards in vivo properties of edible flowers is needed. [ABSTRACT FROM AUTHOR]

Interactions between polyphenols and gut microbiota are indeed a major issue of current interest in food science research. Knowledge in this subject is progressing as the experimental procedures and analysis techniques do. The aim of this article is to critically review the more leading‐edge approaches that have been applied so far in the study of the interactions between grape/wine polyphenols and gut microbiota. This is the case of in vitro dynamic gastrointestinal simulation models that try to mitigate the limitations of simple static models (batch culture fermentations). More complex approaches include the experimentation with animals (mice, rats, pigs, lambs and chicks) and nutritional intervention studies in humans. Main advantages and limitations as well as the most relevant findings achieved by each approach in the study of how grape/wine polyphenols can modulate the composition and/or functionality of gut microbiota, are detailed. Also, common findings obtained by the three approaches (in vitro, animal models and human nutritional interventions) such as the fact that the Firmicutes/Bacteroidetes ratio tends to decrease after the feed/intake/consumption of grape/wine polyphenols are highlighted. Additionally, a nematode (Caenorhabditis elegans) model, previously used for investigating the mechanisms of processes such as aging, neurodegeneration, oxidative stress and inflammation, is presented as an emerging approach for the study of polyphenols interacting gut microbiota. © 2020 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Adaptive (or thermoregulatory model controlled) manikins are useful in quantifying thermal exchanges of the human-clothing-environment system and in simulating human thermophysiological behaviours. Current existing adaptive manikins didn’t take account into the body movement/posture during simulations and this may greatly affect the precision of simulation results. Hence, in this study, the impact of body movement on human physiological responses was investigated using a ‘Newton’ type adaptive thermal manikin and human subjects in a warm environment (i.e., T a  = 30.0 ± 0.5 °C, RH = 60 ± 5%, v a  = 0.17 ± 0.05 m/s). Results demonstrated that the body movement significantly affected the thermal exchange between the clothed manikin and its surrounding environment. Significantly greater mean skin and core temperatures were noted on the standing manikin than those on the walking manikin. In contrast, simulation results obtained from the walking manikin were much closer to human trial data than those obtained from the standing adaptive manikin. Particularly, no significant difference was found in the mean core temperature between the walking adaptive manikin and human subjects. Therefore, the standing adaptive manikin significantly overestimated thermal stress for the two studied conditions. It was thus suggested the body movement should be considered when mimicking human activities on adaptive manikins. [ABSTRACT FROM AUTHOR]

Creation of adhesions in digital flexor tendons after repairing remains a major problem in hand surgery. The adhesions are part of the healing process and produce almost inevitably functional disability following the biological response after tendon injury. To achieve better gliding function of the digital tendons by reducing peritendinous adhesions without adversely affecting the healing process itself, several options, both surgical and pharmacological have been explored. Attempts at reducing postoperative adhesion formation have included early postoperative rehabilitation, low-friction surgical repair techniques, pharmacological antiadhesive reagents, and the use of physical barriers to adhesion formation. Level of Evidence: Not ratable. [ABSTRACT FROM AUTHOR]

A decreasing number of new therapeutic drugs reaching the clinic has led to the publication of regulatory guidelines on human microdosing trials by the European Medicines Agency in 2004 and the US Food and Drug Administration in 2006. Microdosing trials are defined by the administration of 1/100th of the therapeutic dose and designed to investigate basic drug properties. This review investigates the current application of phase 0 trials in medical research. Thirty-three studies found in PubMed and EMBASE were systematically reviewed for aim and analytical method. Pharmacokinetic studies have been a major focus of phase 0 trials, but drug distribution, drug–drug interactions, imaging and pharmacogenomics have also been investigated. Common analytical methods were tandem mass liquid chromatography, accelerator mass spectrometry and positron emission tomography. New ongoing trials are investigating the pharmacodynamics and chemoresistance of marketed drugs, suggesting that the application of phase 0 trials is still evolving. [ABSTRACT FROM AUTHOR]

The article discusses the application of dietary n-3 PUFA in cancer treatment. It mentions that n-3 PUFA is a hydrocarbon chain that contains two or more double bonds. It mentions that n-3 PUFA does not induce toxic or carcinogenic effects in humans. It notes the effectivity of n-3 PUFA in cancer patients as a single therapy.

Abstract Immunization of animals is one of the key standards for evaluation of vaccine efficacy prior to human clinical trials. However, vaccine organizations should not over-interpret these results as protective efficacy in animals may not be relevant in humans. Screening of vaccine candidates has recently been performed by several in vitro human models. A properly designed in vitro approach opens new venues for vaccine development. [ABSTRACT FROM AUTHOR]

Functional Micro-Dispensers (FMDs) based on Micro-Electro-Mechanical-Systems (MEMS) were designed to deliver spatial repellents that reduce the ability of mosquitoes to feed on humans. FMDs were integrated with fabrics as functional materials for protection against mosquito bites. The use of MEMS devices provides an unprecedented control over the release kinetics by means of integration with electronics for selective and timely activation of each device to perform controlled release of pesticides in air. In addition, because MEMS manufacturing techniques evolved from the microelectronic industry, FMDs can be mass produced at very low cost. Trials using FMDs that contained transfluthrin improved protection against mosquito feeding in human subjects above that of permethrin-treated uniform fabric worn on the arm of the volunteer. The overall reduction in feeding was approximately 90% compared to the untreated fabric control, and about 50% reduction compared to the permethrin-treated fabric control. The devices were efficacious over course of 32 days. FMDs have the potential for a simple and cost-effective implementation for mass adoption as wearable devices integrated in fabrics as active functional materials. [ABSTRACT FROM AUTHOR]

Purpose: Retinal gene therapy trials are currently ongoing in a small number of inherited retinal disorders and this number is expected to rise significantly. The aim of this study was to analyze the psychological aspects of patients with RPE65 deficiency awaiting potential enrollment in gene therapy trials. Methods: Five patients with genetically proven RPE65 deficiency took part in this study. They were asked to complete the German versions of (i) the Patient Health Questionnaire (PHQ-D), (ii) the National Eye Institute Visual Function Questionnaire (NEI-VFQ), (iii) the Shared Decision Making Questionnaire (PEF-FB-9), and (iv) the Autonomy Preference Index (API-Dm), and in addition they took part in qualitative interviews. Results: The evaluations of the questionnaires and the interviews showed that the patients have quite high information needs and wish to take part in medical decisions. The perspective to participate in gene therapy trials does not seem to cause pronounced worries. Only the insecurity about if and when enrollment in a trial takes place may be burdensome. Discussion: This study generated important data about the psychological situation of patients awaiting potential enrollment in clinical trials, which can be used to improve patient care in the increasing number of future gene therapy trials around the world. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Leber congenital amaurosis (LCA) is a congenital retinal dystrophy that results in significant and often severe vision loss at an early age. Comprehensive analysis of the genetic mutations and phenotypic correlations in LCA patients has allowed for significant improvements in understanding molecular pathways of photoreceptor degeneration and dysfunction. The purpose of this article is to review the literature on the subject of retinal gene therapy for LCA, including historical descriptions, preclinical animal studies, and human clinical trials. Methods: A literature search of peer-reviewed and indexed publications from 1996-2011 using the PubMed search engine was performed. Key terms included 'Leber congenital amaurosis', LCA, RPE65, 'cone-rod dystrophy', 'gene therapy', and 'human trials' in various combinations. Seminal articles prior to 1996 were selected from primary sources and reviews from the initial search. Articles were chosen based on pertinence to clinical, genetic, and therapeutic topics reviewed in this manuscript. Fundus photographs from LCA patients were obtained retrospectively from the clinical practice of one of the authors (R.A.S). Results: Herein, we reviewed the literature on LCA as a genetic disease, the results of human gene therapy trials to date, and possible future directions towards treating inherited retinal diseases at the genetic level. Original descriptions of LCA by Theodor Leber and subsequent research demonstrate the severity of this disease with early-onset blindness. Discoveries of the causative heritable mutations revealed genes and protein products involved in photoreceptor development and visual transduction. Animal models have provided a means to test novel therapeutic strategies, namely gene therapy. Stemming from these experiments, three independent clinical trials tested the safety of subretinal delivery of viral gene therapy to patients with mutations in the RPE65 gene. More recently, efficacy studies have been conducted with encouraging results. Conclusions: Initial safety studies indicated promising results of subretinal delivery of viral vector with subclinical immunologic or surgical sequelae. Overall, these initial studies demonstrate that viral vector gene therapy results are very promising, safe, and effective. Future studies measuring potential improvement in photoreceptor function may rely on recent advances in retinal imaging and electrophysiologic testing. [ABSTRACT FROM AUTHOR]

Immunotherapy aims to assist the natural immune system in achieving control over viral infection. Various immunotherapy formats have been evaluated in either therapy-naive or therapy-experienced HIV-infected patients over the last 20 years. These formats included non-antigen specific strategies such as cytokines that stimulate immunity or suppress the viral replication, as well as antibodies that block negative regulatory pathways. A number of HIV-specific therapeutic vaccinations have also been proposed, using in vivo injection of inactivated virus, plasmid DNA encoding HIV antigens, or recombinant viral vectors containing HIV genes. A specific format of therapeutic vaccines consists of ex vivo loading of autologous dendritic cells with one of the above mentioned antigenic formats or mRNA encoding HIV antigens. This review provides an extensive overview of the background and rationale of these different therapeutic attempts and discusses the results of trials in the SIV macaque model and in patients. To date success has been limited, which could be explained by insufficient quality or strength of the induced immune responses, incomplete coverage of HIV variability and/or inappropriate immune activation, with ensuing increased susceptibility of target cells. Future attempts at therapeutic vaccination should ideally be performed under the protection of highly active antiretroviral drugs in patients with a recovered immune system. Risks for immune escape should be limited by a better coverage of the HIV variability, using either conserved or mosaic sequences. Appropriate molecular adjuvants should be included to enhance the quality and strength of the responses, without inducing inappropriate immune activation. Finally, to achieve a long-lasting effect on viral control (i.e. a "functional cure") it is likely that these immune interventions should be combined with anti-latency drugs and/or gene therapy. [ABSTRACT FROM AUTHOR]

Methotrexate (MTX) is the most important drug for treating rheumatoid arthritis (RA). It has been stated that cytokines play an important role in the pathogenesis of RA, and that cytokine levels increase and show 24-h rhythms in RA patients. Previously, we found that arthritis was relieved after the administration of MTX at specific times in synchronization with the 24-h rhythm of tumor necrosis factor (TNF)-αα in collagen-induced arthritis (CIA) animals. Based on our findings in an earlier study of the dosing time--dependent effects of MTX in MRL/lpr mice, which develop autoimmune disorders that share similarities with human RA, we examined here the utility of MTX chronotherapy in Japanese RA patients. In an initial animal modeling study, we collected blood from MRL/lpr mice at different times (2, 6, 10, 14, 18, or 22 ours fter the ight was turned n [HALO]), and we measured TNF-αα mRNA expression in leukocytes. MTX was administered to the mice at two different dosing times (6 or 18 HALO), and various blood parameters were measured to estimate arthritis activity. TNF-αα mRNA levels showed a clear 24-h rhythm with a peak at 22 HALO and a trough at 18 HALO after RA had developed. In these MRL/lpr mice, inflammation and TNF-αα were markedly reduced when the MTX dosing time was matched to the time (18 HALO) when the TNF-αα level began to increase. We then applied these findings to Japanese RA patients by switching them from the standard MTX three times/wk (day 1: after breakfast and supper; day 2: after breakfast schedule), to chronotherapy, in which the dose and number of doses/wk were not changed but MTX was administered once-a-day at bedtime. Disease Activity Score (DAS)28, modified health assessment questionnaire (MHAQ), and adverse effects were assessed. With MTX chronotherapy, DAS28, which is commonly used to quantitatively assess RA symptoms, was significantly improved at all follow-up clinical visit times compared with the baseline (vs. 1 mo: p == .0197, 2 mos: p == .0107, 3 mos: p == .0087). Significant symptom recovery was observed in 41.2%% of patients, and 23.5%% of patients achieved clinical remission during the 3 mos of follow-up. Functional capacity of RA patients, as indicated by the MHAQ, was markedly improved by chronotherapy. There were no severe adverse effects. Thus, we demonstrated (i) inflammation and plasma TNF-αα concentrations were significantly reduced in MRL/lpr mice treated with MTX at 18 HALO, the time when TNF-αα mRNA level began to increase; and (ii) MTX bedtime chronotherapy was safe, markedly reduced disease activity, and improved the functional capacity of RA patients. The findings on RA patients show that bedtime MTX chronotherapy can improve RA symptoms compared to the current standard dosing methods. (Author correspondence: ) [ABSTRACT FROM AUTHOR]

Abstract: Numerous individuals and institutions throughout the world have contributed to the development of hematopoietic stem cell transplantation (HSCT) for autoimmune diseases. In this review, we will summarize what we have learned at our own institution (Northwestern University), and how it has guided our therapy. An emphasis will be placed on both the scientific basis for the development of autologous hematopoietic stem cell transplantation and a summary of the data in a variety of human diseases. [Copyright &y& Elsevier]

Antisense oligonucleotides have been widely used to specifically and selectively downregulate gene expression at the messenger RNA level. Even though oligonucleotides are commonly used in laboratories and clinical trials, they can induce non-specific effects that can lead to misinterpretation of experimentally-derived results. This review summarizes precautions one should take when using oligonucleotides. In addition, the role of one oligonucleotide, G3139, which is targeted to the coding region of bcl-2 messenger RNA, in inhibiting tumor progression in vitro and in clinical trials, is described. [Copyright &y& Elsevier]

Convincing lipid-lowering effects of the fructooligosaccharide inulin have been demonstrated in animals, yet attempts to reproduce similar effects in humans have generated conflicting results. This may be because of the much lower doses used in humans as a result of the adverse gastrointestinal symptoms exhibited by most subjects consuming daily doses in excess of 30 g. Two studies that fed either oligofructose (20 g/d) or inulin (14 g/d) observed no effect on fasting total, LDL or HDL cholesterol, or serum triglycerides. Two other studies that fed inulin either in a breakfast cereal (9 g/d) or as a powdered addition to beverages and meals (10 g/d) reported similar reductions in fasting triglycerides (-27 and -19%, respectively). In one of these studies, total and LDL cholesterol concentrations were also modestly reduced (5 and 7%, respectively). Because animal studies have identified inhibition of hepatic fatty acid synthesis as the major site of action for the triglyceride-lowering effects of inulin, and because this pathway is relatively inactive in humans unless a high carbohydrate diet is fed, future attempts to demonstrate lipid-lowering effects of inulin should consider the nature of the background diet as a determinant of response. [ABSTRACT FROM AUTHOR]