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Application of Drug Repurposing Approach for Therapeutic Intervention of Inflammatory Bowel Disease.Current Reviews in Clinical and... 2024Inflammatory bowel disease (IBD), represented by Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder of the gastrointestinal tract (GIT)... (Review)
Review
Inflammatory bowel disease (IBD), represented by Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder of the gastrointestinal tract (GIT) characterized by chronic relapsing intestinal inflammation, abdominal pain, cramping, loss of appetite, fatigue, diarrhoea, and weight loss. Although the etiology of IBD remains unclear, it is believed to be an interaction between genes, and environmental factors, such as an imbalance of the intestinal microbiota, changing food habits, an ultra-hygiene environment, and an inappropriate immune system. The development of novel effective therapies is stymied by a lack of understanding of the aetiology of IBD. The current therapy involves the use of aminosalicylates, immunosuppressants, and corticosteroids that can effectively manage symptoms, induce and sustain remission, prevent complications, modify the course of the disease, provide diverse treatment options, showcase advancements in biologic therapies, and enhance the overall quality of life. However, the efficacy of current therapy is overshadowed by a plethora of adverse effects, such as loss of weight, mood swings, skin issues, loss of bone density, higher vulnerability to infections, and elevated blood pressure. Biologicals, like anti-tumour necrosis factor agents, can stimulate an autoimmune response in certain individuals that may diminish the effectiveness of the medication over time, necessitating a switch to alternative treatments. The response of IBD patients to current drug therapy is quite varied, which can lead to disease flares that underlines the urgent need to explore alternative treatment option to address the unmet need of developing new treatment strategies for IBD with high efficacy and fewer adverse effects. Drug repurposing is a novel strategy where existing drugs that have already been validated safe in patients for the management of certain diseases are redeployed to treat other, unindicated diseases. The present narrative review focuses on potential drug candidates that could be repurposed for the management of IBD using on-target and off-target strategies. It covers their preclinical, clinical assessment, mechanism of action, and safety profiles, and forecasts their appropriateness in the management of IBD. The review presents useful insights into the most promising candidates for repurposing, like anti-inflammatory and anti-apoptotic troxerutin, which has been found to improve the DSS-induced colitis in rats, an antiosteoarthritic drug diacetylrhein that has been found to have remarkable ameliorating effects on DSS-induced colitis via anti-oxidant and anti- inflammatory properties and by influencing both apoptosis and pyroptosis. Topiramate, an antiepileptic and anticonvulsant drug, has remarkably decreased overall pathophysiological and histopathological events in the experimental model of IBD in rodents by its cytokine inhibitory action.
Topics: Humans; Drug Repositioning; Animals; Inflammatory Bowel Diseases; Colitis, Ulcerative; Crohn Disease; Anti-Inflammatory Agents; Gastrointestinal Agents
PubMed: 37859409
DOI: 10.2174/0127724328245156231008154045 -
Journal of Neurotrauma Mar 2024Naturally occurring life stages in women are associated with changes in the milieu of endogenous ovarian hormones. Women of childbearing age may be exposed to exogenous... (Review)
Review
Naturally occurring life stages in women are associated with changes in the milieu of endogenous ovarian hormones. Women of childbearing age may be exposed to exogenous ovarian hormone(s) because of their use of varying combinations of estrogen and progesterone hormones-containing oral contraceptives (OC; also known as "the pill"). If women have central nervous system (CNS) injury such as spinal cord injury (SCI) and traumatic brain injury (TBI) during their childbearing age, they are likely to retain their reproductive capabilities and may use OC. Many deleterious side effects of long-term OC use have been reported, such as aberrant blood clotting and endothelial dysfunction that consequently increase the risk of myocardial infarction, venous thromboembolism, and ischemic brain injury. Although controversial, studies have suggested that OC use is associated with neuropsychiatric ramifications, including uncontrollable mood swings and poorer cognitive performance. Our understanding about how the combination of endogenous hormones and OC-conferred exogenous hormones affect outcomes after CNS injuries remains limited. Therefore, understanding the impact of OC use on CNS injury outcomes needs further investigation to reveal underlying mechanisms, promote reporting in clinical or epidemiological studies, and raise awareness of possible compounded consequences. The goal of the current review is to discuss the impacts of CNS injury on endogenous ovarian hormones and vice-versa, as well as the putative consequences of exogenous ovarian hormones (OC) on the CNS to identify potential gaps in our knowledge to consider for future laboratory, epidemiological, and clinical studies.
Topics: Female; Humans; Hormonal Contraception; Trauma, Nervous System; Central Nervous System; Brain Injuries, Traumatic; Estrogens
PubMed: 37975282
DOI: 10.1089/neu.2023.0219 -
Brazilian Journal of Physical Therapy 2023Individuals with Parkinson's disease present arm swing alterations that can adversely affect their locomotion. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Individuals with Parkinson's disease present arm swing alterations that can adversely affect their locomotion.
OBJECTIVE
To identify differences in arm swing asymmetry (ASA) between individuals with Parkinson's disease (PD) and healthy individuals and to investigate the relationship between ASA, temporal-spatial gait parameters, and disease progression.
METHODS
A literature search was conducted in PubMed, Scopus, ProQuest, Web of Science, and EBSCOhost up to February 2023. Cross-sectional studies evaluating parameters of arm swing (AS) and ASA were included. Methodological quality was assessed using the Critical Appraisal Checklist, and the quality of the evidence was measured with a modified Grading of Recommendations Assessment, Development, and Evaluation.
RESULTS
Fourteen studies were included in the systematic review (1130 participants). Irrespective of the medication phase (ON or OFF) and the type of walk test employed, the meta-analysis showed moderate-quality evidence that individuals with PD have increased ASA amplitude (SMD = 0.84; 95% CI: 0.69, 0.99; I²= 0%).Very low-quality evidence suggests higher ASA velocity (SMD=0.64; 95% CI: 0.24, 1.05; I²=59%) and lower AS amplitude on both the most affected (ES = -1.99, 95% CI: -3.04, -0.94, I: 91%) and the least affected sides (ES = -0.75, 95% CI: -1.05, -0.44; I²=66%). Meta-regression indicated that ASA is inversely related to disease duration (Z: -2.4892, P< 0.05) and motor symptoms progression (Z: -2.1336, P< 0.05).
CONCLUSIONS
Regardless of the medication phase and the type of walk test employed, individuals with PD exhibited greater ASA and decreased AS amplitude than healthy individuals. ASA decreases as the disease progresses and symptoms worsen.
Topics: Humans; Parkinson Disease; Walking; Arm; Cross-Sectional Studies; Biomechanical Phenomena; Gait
PubMed: 37980716
DOI: 10.1016/j.bjpt.2023.100559 -
Der Nervenarzt Mar 2024Premenstrual syndrome and premenstrual dysphoric disorder become episodically manifest during the second half of the female menstrual cycle and are characterized by... (Review)
Review
Premenstrual syndrome and premenstrual dysphoric disorder become episodically manifest during the second half of the female menstrual cycle and are characterized by psychological and physical symptoms causing relevant functional and social impairments. Mood swings, depression and dysphoria are associated depressive symptoms. Therefore, affective disorders should be considered as a differential diagnosis. Of women in reproductive age 3-8% suffer from premenstrual syndrome and 2% of women are affected by premenstrual dysphoric disorder. Genetic and sociobiographical risk factors are discussed. Furthermore, genetic polymorphisms of specific hormone receptors are considered to be genetic risk factors. From a pathophysiological perspective premenstrual syndrome and premenstrual dysphoric disorder are caused by a complex interaction between cyclic changes of ovarian steroids and central neurotransmitters. An imbalance of estrogen and progesterone in the luteal phase is believed to cause the symptoms. Therefore, the first treatment approach consists of regulation of the menstrual cycle or luteal support with progesterone or synthetic progestins even if their effectiveness has not yet been proven in randomized controlled studies and meta-analyses. The administration of combined oral contraceptives is also an option. Especially treatment with selective serotonin reuptake inhibitors (SSRI) represent an evidence-based approach. In severe cases the administration of gonadotropin releasing hormone (GnRH) agonists with add back treatment can also be considered. In the field of affective disorders premenstrual syndromes represent clinically relevant differential diagnoses and comorbidities, which confront the treating physician with particular clinical challenges. Therefore, this literature review gives the readership a clinical orientation for dealing with these disorders.
Topics: Female; Humans; Child, Preschool; Premenstrual Dysphoric Disorder; Progesterone; Premenstrual Syndrome; Mood Disorders; Anxiety
PubMed: 38393358
DOI: 10.1007/s00115-024-01625-5 -
BMC Sports Science, Medicine &... Nov 2023The effect of listening to audiobooks, podcasts, and other audio files while walking on gait performance has not been well studied. Although the number of audio users is...
BACKGROUND
The effect of listening to audiobooks, podcasts, and other audio files while walking on gait performance has not been well studied. Although the number of audio users is growing annually. Evidence suggests that a posture-first strategy contributes to gait stability in healthy individuals during dual-task conditions, but this effect may be diminished when the cognitive task is consciously prioritized.
OBJECTIVES
To study the effect of listening to an audiobook while walking, as a daily life-like dual-task, on spatiotemporal gait parameters.
METHODS
Forty young healthy (24.05 ± 3.66) subjects participated in the study. Spatiotemporal gait parameters were measured for 5 min on a treadmill once without (single-task) and once while listening to an audiobook through over-ear headphones (dual-task). Measured parameters included spatiotemporal parameters, gait phases, maximum pressure, and dual-task cost. Data were statistically analyzed using SPSS software.
RESULTS
There were no significant differences in any of the studied parameters between the single- and dual-task conditions, even though the subjective cognitive load of listening to audiobooks while walking was high. However, participants with different habits had significant differences in gait phases and maximum pressure. Rare listeners had a shorter stance phase, a longer swing phase, and a higher maximum pressure on the dominant heel. They also had significant differences in dual-task costs.
CONCLUSION
No differences in the spatiotemporal gait parameters for walking with and without listening to audiobooks, as a daily life-like dual-task, were observed. However, the difference between participants who listened rarely and participants who listened often may confirm the "posture first" strategy in young healthy people.
TRIAL REGISTRATION
DRKS00025837, retrospectively registered on 23.11.2021.
PubMed: 38001528
DOI: 10.1186/s13102-023-00773-6 -
Maturitas Jul 2024Water pollution exerts a negative impact on the health of both women and men, inducing hormonal changes, accelerating aging, and consequently leading to the premature... (Review)
Review
Water pollution exerts a negative impact on the health of both women and men, inducing hormonal changes, accelerating aging, and consequently leading to the premature onset of age-related health problems. Water pollutants can in general be classified as chemical (both organic and inorganic), physical, and biological agents. Certain chemical pollutants have been found to disrupt hormonal balance by blocking, mimicking, or disrupting functions within the intricate homeostasis of the human body. Moreover, certain water pollutants, including specific pesticides and industrial chemicals, have been associated with neurological and psychiatric disorders, such as mood swings, depression, cognitive decline, and anxiety, impacting both women and men. Water pollution is also associated with physical ailments, such as diarrhea, skin diseases, malnutrition, and cancer. Exposure to specific pollutants may promote premature menopause and vasomotor symptoms, elevate the risk of cardiovascular disease, and reduce bone density. In men, exposure to water pollution has been shown to reduce LH, FSH, and testosterone serum levels. The oxidative stress induced by pollutants prompts apoptosis of Sertoli and germ cells, inhibiting spermatogenesis and altering the normal morphology and concentration of sperm. Environmental estrogens further contribute to reduced sperm counts, reproductive system disruptions, and the feminization of male traits. Studies affirm that men generally exhibit a lower susceptibility than women to hormonal changes and health issues attributed to water pollutants. This discrepancy may be attributed to the varied water-related activities which have traditionally been undertaken by women, as well as differences in immune responses between genders. The implementation of effective measures to control water pollution and interventions aimed at safeguarding and enhancing the well-being of the aging population is imperative. The improvement of drinking water quality has emerged as a potential public health effort with the capacity to curtail the onset of cognitive impairment and dementia in an aging population.
Topics: Humans; Male; Female; Aging; Water Pollution; Aged; Water Pollutants, Chemical
PubMed: 38555759
DOI: 10.1016/j.maturitas.2024.107981 -
Pediatric Dermatology Mar 2024Isotretinoin treatment for acne can reduce adverse psychiatric outcomes in adults, but there has been little investigation of the incidence of psychiatric outcomes in...
BACKGROUND
Isotretinoin treatment for acne can reduce adverse psychiatric outcomes in adults, but there has been little investigation of the incidence of psychiatric outcomes in treated adolescents.
METHODS
This retrospective cohort study using the Rochester Epidemiology Project identified 606 patients aged 12-18 prescribed isotretinoin over a 10-year period between January 1, 2008 and December 31, 2017. Medical records were reviewed to identify psychiatric diagnoses before and during isotretinoin therapy, as well as psychiatric symptoms not captured by formal diagnoses and changes to isotretinoin dosing because of psychiatric diagnoses or symptoms.
RESULTS
One hundred seventy-seven (29.2%) had a psychiatric diagnosis prior to isotretinoin initiation, but 98 (16.2%) had a new psychiatric diagnosis or psychiatric symptom while taking isotretinoin. Patients with a psychiatric history were no more likely than those without to receive a new psychiatric diagnosis during treatment (4.5% vs. 3.7%; p = .650), but did experience more psychiatric symptoms, primarily low mood and mood swings (23.7% vs. 7.7%; p < .001). Only 25.5% of the 98 with a new psychiatric diagnosis or psychiatric symptom had a subsequent dose change. A dose change was more likely if patients received a new psychiatric diagnosis (41.7% vs. 20.3%; p = .037) or patients did not have a psychosocial explanation for psychiatric symptoms (34.4% vs. 10.8%; p = .009).
CONCLUSIONS
A substantial proportion of adolescent patients prescribed isotretinoin had a prior psychiatric diagnosis. This predicts more psychiatric symptoms during isotretinoin treatment. Adolescents with a psychiatric history who have worsening symptoms and those with new-onset psychiatric symptoms would benefit from close monitoring while taking isotretinoin.
PubMed: 38500340
DOI: 10.1111/pde.15595 -
Gait & Posture Jul 2023Thirty percent of adults in the United States use wearable fitness devices as of 2020 [1], such as fitness watches, to monitor and track health and physical activity...
BACKGROUND
Thirty percent of adults in the United States use wearable fitness devices as of 2020 [1], such as fitness watches, to monitor and track health and physical activity parameters. Physical changes during pregnancy may impact wrist worn device accuracy. The arms may be needed as compensation during walking because thorax axial rotation may be inhibited by pelvic tilt during pregnancy [2].
METHODS
To examine arm motion changes, twenty-three pregnant women (28 ± 4 y) were tested in four-week intervals ( ± 2 weeks) at 18-, 22-, 26-, 30- and 34-weeks' gestation. Kinematic data were measured during self-selected speed walking. Segment angles and angular velocities were analyzed over time. Linear regressions were used to analyze the correlations between arm motion and the other kinematic variables.
RESULTS
Arm range of motion significantly increased (p = 0.006) over gestation, but leg, thorax, and pelvis range of motions did not significantly change. Arm range of motion was correlated with pelvis (r =0.311, p = 0.001, β = 1.724) and leg (r = 0.285, p = 0.004, β = 1.520) range of motion and gait velocity (r =0.566, p = 0.001, β = 39.110). Arm velocities significantly increased (p < 0.012), as did leg velocities (p < 0.022) over gestation time, but thorax and pelvis rotational velocities did not significantly change over time. Arm velocity was correlated with leg velocity in both flexion (r =0.598, p = 0.001, β = 1.61) and extension (r =0.568, p = 0.001, β = 1.35).
SIGNIFICANCE
Arm swing increases over the course of gestation during walking, which does not follow the exact pattern of changes seen in the legs, thorax, and pelvis. These results show that a typical gait analysis of lower body motions may miss important biomechanical changes or compensations at different points over pregnancy. Future studies should examine why these changes may occur. Studies should also be conducted to see if arm changes impact outcome parameters from fitness watches and affect their validity as an exercise tracker during pregnancy.
Topics: Adult; Female; Humans; Pregnancy; Biomechanical Phenomena; Gait; Walking; Pelvis; Rotation; Arm; Range of Motion, Articular
PubMed: 37356228
DOI: 10.1016/j.gaitpost.2023.06.017 -
PloS One 2024Observational studies have previously shown a potential link between psycho-emotional disorders, such as mood swings, highly strung, anxious feelings, and...
BACKGROUND
Observational studies have previously shown a potential link between psycho-emotional disorders, such as mood swings, highly strung, anxious feelings, and gastroesophageal reflux disease (GERD). However, the credibility of these associations could be influenced by various confounding factors. Consequently, our study sought to employ a Mendelian randomization (MR) approach to elucidate a potential causal relationship between psycho-emotional disorders and GERD.
METHOD
Information on independent genetic variants linked to mood swings, highly strung, and anxious feelings was gathered from European populations participating in the IEU Open GWAS research. The FinnGen Consortium provided the genome-wide association study (GWAS) summary statistics for GERD. Our analysis employed the inverse variance weighted (IVW) method under the random effects model as the main analytical method. To further bolster our findings, we employed the weighted median and MR Egger methods. In addition, we conducted a series of sensitivity analyses.
RESULTS
Our study supports the existence of a causal relationship between psycho-emotional disorders and GERD. Mood swings, highly strung, and anxious feelings adversely affected GERD risk (mood swings: OR 2.21, 95% CI 1.19-5.59, p = 3.09 × 10-2; highly strung: OR 5.63, 95% CI 1.77-17.94, p = 3.42 × 10-3; anxious feelings: OR 2.48, 95% CI 1.08-4.33, p = 2.89 × 10-2).
CONCLUSION
This Mendelian randomization study provides robust support for the notion that mood swings, highly strung and anxious feelings, are associated with an increased risk of developing GERD.
Topics: Humans; Gastroesophageal Reflux; Mendelian Randomization Analysis; Genome-Wide Association Study; Anxiety; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease
PubMed: 38709755
DOI: 10.1371/journal.pone.0302469 -
Heliyon Feb 2024Alzheimer's disease is a neurological disorder that causes increased memory loss, mood swings, behavioral disorders, and disruptions in daily activities. Polymer... (Review)
Review
Alzheimer's disease is a neurological disorder that causes increased memory loss, mood swings, behavioral disorders, and disruptions in daily activities. Polymer scaffolds for the brain have been grown under laboratory, physiological, and pathological circumstances because of the limitations of conventional treatments for patients with central nervous system diseases. The blood-brain barrier prevents medications from entering the brain, challenging AD treatment. Numerous biomaterials such as biomolecules, polymers, inorganic metals, and metal oxide nanoparticles have been used to transport therapeutic medicines into the nervous system. Incorporating biocompatible materials that support neurogenesis through a combination of topographical, pharmacological, and mechanical stimuli has also shown promise for the transfer of cells to replenish dopaminergic neurons. Components made of naturally occurring biodegradable polymers are appropriate for the regeneration of nerve tissue. The ability of natural-based materials (biomaterials) has been shown to promote endogenous cell development after implantation. Also, strategic functionalization of polymeric nanocarriers could be employed for treating AD. In particular, nanoparticles could resolve Aβ aggregation and thus help cure Alzheimer's disease. Drug moieties can be effectively directed to the brain by utilizing nano-based systems and diverse colloidal carriers, including hydrogels and biodegradable scaffolds. Notably, early investigations employing neural stem cells have yielded promising results, further emphasizing the potential advancements in this field. Few studies have fully leveraged the combination of cells with cutting-edge biomaterials. This study provides a comprehensive overview of prior research, highlighting the pivotal role of biomaterials as sophisticated drug carriers. It delves into various intelligent drug delivery systems, encompassing pH and thermo-triggered mechanisms, polymeric and lipid carriers, inorganic nanoparticles, and other vectors. The discussion synthesizes existing knowledge and underscores the transformative impact of these biomaterials in devising innovative strategies, augmenting current therapeutic methodologies, and shaping new paradigms in the realm of Alzheimer's disease treatment.
PubMed: 38434059
DOI: 10.1016/j.heliyon.2024.e26351