Contractions in smooth muscle cells are initiated by elevation of cytosolic Ca2+. It is of interest to measure Ca2+ signals in these cells. Transgenic Acta2-GCaMP8.1-mVermilion (GCaMP) mice express a genetically encoded intracellular fluorescent Ca2+ indicator in smooth muscle cells, have been developed to facilitate the study of Ca2+. However, there is a concern that the GCaMP Ca2+ indicator might buffer Ca2+ and interfere with the signals it is designed to measure. Therefore, the aim of this study was to compare tension responses in GCaMP and wild type (WT) mice to determine if the former behaved normally. Electrical field stimulation (EFS) using 2Hz pulses for 1 second, with intervals of 100 and 10 seconds, was applied to evoke transient contractions in the bronchial smooth muscle from GCaMP and WT mice. An enhancement in contraction amplitude was observed in both groups upon switching from 100s intervals to 10s. Results indicate this is due to sensitisation of the muscarinic M3 receptor (M3R)-mediated responses by recruitment of muscarinic M2 receptors (M2R). The contraction amplitudes in the GCaMP mice were smaller than in the WT, but they were of longer duration. In GCaMP, there was an increase in the baseline when the time interval changed from 100s to 10s, it could be a result of summation of contractions preventing return to baseline. Also, the degree of enhancement upon switching from 100s to 10s stimulus intervals was greater in GCaMP mice. In conclusion, marked differences in contraction were seen in GCaMP mice compared to WT, therefore results from these animals should be interpreted with caution.
The aim of the following work was to investigate and compare curcumin and cayenne pepper in microbeads composed of sodium alginate (SA) crosslinked with montmorillonite (MMT) to act as drug carriers and their antimicrobial resistance. The microbeads were prepared through ion-exchange in multivalent solutions of CaCl2, MgCl2 and AlCl3. The microbeads were characterized by Scanning Electron Microscopy (SEM), Energy Dispersive X-ray analysis (EDX) and the time required for intercalation of curcumin and cayenne pepper with MMT. Simulated intestinal fluid (pH 7.3) and gastric fluid (pH 1.2) at 37°C were used for comparison in swelling studies. Gram-positive S. aureus and Gram-negative E. coli were used for antimicrobial resistance comparison of the multivalent microbeads containing curcumin and cayenne pepper. The results found that curcumin took less time to intercalate with MMT compared to cayenne pepper. Swelling results indicated that pH played a direct role in the uptake of water in the beads with pH 1.2 causing the least amount of water uptake. It was also observed from these results that the MgCl2 beads had the greatest swelling degree and the AlCl3 beads had the lowest swelling degree in both pH1.2 and pH 7.3. EDX results provided information on the elemental composition of the microbeads. SEM results showed the MgCl2 microbeads for both curcumin and cayenne pepper, appeared the roughest allowing for greater water uptake, while the AlCl3 microbeads had a smoother surface leading to less water uptake which correlated with the swelling measurement results. The antimicrobial tests showed the AlCl3 beads for both curcumin and cayenne pepper had the greatest zones of inhibition with curcumin providing the best resistance. The combined results suggest that the beads produced may be best suited for intestinal drug delivery with the curcumin AlCl3 beads providing the overall best results for antimicrobial resistance and drug carrying ability.
Review: Obesity is a global threat to human health that is precipitating epidemically, with almost 2 billion adults categorised as overweight or obese in 2016. Ireland has one of the highest reports of obesity in Europe with 60% of Irish adults reported as overweight or obese. Inflammation plays an integral role in disease pathogenesis and is a major hallmark of obesity and obesity-related secondary co-morbidities. Obesity-related inflammation can precipitate several diseases, such breast cancer, insulin resistance, type II diabetes and cardiovascular issues. As obesity puts human health at inherent risk, the regulation of obesity-related inflammation is therefore a necessary component to reduce disease onset, and progression, and manage symptoms. Targeting key mediators in the chronic low-grade inflammation seen in obesity may provide insight into novel obesity treatment and management approaches. For example, targeting cytokine regulation is key to regulating inflammation, by reducing the expression of pro-inflammatory cytokines, and increasing the expression of anti-inflammatory cytokines. The most common approach to obesity management and treatment includes clinical and pharmacological interventions, focusing on avenues such as surgery, weight loss management programs, and synthetic medications like semaglutides (e.g. Wegovy) and glucocorticoids (e.g. dexamethasone). The complex clinical and regulatory history of these anti-obesity avenues has derived the investigation into alternative strategies utilising natural resources. Consequently, research into the anti-inflammatory and anti-obesity properties of compounds like curcumin has heightened in recent years. Curcumin is a promising therapeutic approach in regulating inflammatory disease through the modulation of key disease mediators, such as pro- and anti-inflammatory cytokines, microRNAs (miRNAs) responsible for gene expression, and intracellular signalling pathways. Although the potential therapeutic benefits of curcumin are significant, there are several unknowns and limitations to its activity that remain. This review will journey through the inflammatory foundations of obesity, providing information on anti-obesity strategies currently available and closing with curcumin as an alternative natural therapeutic approach to treating obesity.
Background/ Objectives: Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction with a multi-faceted pathogenesis. A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs), known as a low FODMAP diet (LFD), is an effective management option for many, however, it is complex, costly, and restrictive. A milder, modified low FODMAP diet (MLFD) is one suggested alternative, however, data on this approach is lacking. This study aimed to explore the efficacy of a MLFD versus a LFD on symptom improvement in IBS. Subjects/ Methods: Routine clinical data collected on individuals with a Rome IV IBS diagnosis between August 2018 and October 2022 from a specialist-dietitian led IBS clinic in Blackrock Health, Dublin was retrospectively analysed. Individuals had been recommended to follow a LFD or a MLFD for four weeks. Information on symptoms was collected using a modified gastrointestinal symptom rating scale (mGSRS) at initial assessment and at 4-week follow-up. Data was analysed using SPSS. Results: Data on 108 individuals was available; 63 were recommended to follow the LFD, 45 the MLFD. Both the MLFD and LFD achieved significant improvements in mGSRS scores (p Conclusion: The MLFD was associated with significant improvements in symptoms of IBS and normalised stool type. These findings suggest that such stringent restriction as seen in the LFD is not necessary as management options evolve. The future of IBS therapy should consider more liberalised approaches.
Introduction: The recent reclassification of aspartame as a Group 2B hazard by the International Agency for Research on Cancer, along with studies suggesting links to cancer, has raised concerns and prompted further investigation. Evidence suggests that aspartame exposure may alter p53 and BAX gene expression, affecting apoptosis in cancer cells. This study aims to examine how aspartame exposure affects p53 and BAX gene expression in normal mouse stomach tissue, shedding light on cellular stress and apoptosis mechanisms. Methods: Mice were sacrificed, and stomach tissue was excised and divided into control and treatment groups. RNA extraction was carried out in the control and aspartame-treated mouse stomach tissue. The expression of 2 target genes (p53 and BAX) and 2 potential housekeeping genes (UBC and beta-actin) were determined using PCR and qPCR. The statistical significance of the relative fold changes was assessed with two-sample t-tests in Microsoft Excel. Findings: Treatment with 1mg/ml of aspartame resulted in the upregulation of p53 and BAX, along with the downregulation of UBC relative to the control untreated mouse stomach tissue. Conclusion: In conclusion, these preliminary findings demonstrate that exposure to high concentrations of aspartame (1mg/ml), equivalent to the upper limit of the ADI of 40 mg/kg body weight, significantly upregulated p53 and BAX. This implies a possible connection between aspartame exposure and cellular stress, including increased apoptosis signalling, potentially contributing to cancer development, especially via BAX. However, limitations include small sample size and challenges associated with poor RNA quality, which could have influenced the results.
Purpose Metastatic prostate cancer is associated with poor survival rate and limited treatment options. Overexpression of c-Myc and BIRC5 has been reported in prostate cancer cells which contribute to the development of the tumour environment. The specific tumour receptor mechanism of the death ligand TRAIL (tumour necrosis factor related apoptosis inducing ligand) has attracted remarkable therapeutic interest. However, many cancer cells are resistant to TRAIL monotherapy. A novel microtubule-targeting agent, PBOX-15 is known to exhibit anti-tumour activity in cancer cell lines including those with multi-drug resistance. Previous studies demonstrated that PBOX-15 is capable in sensitising cancer cells to TRAIL-mediated cell death by upregulation of death receptors and downregulation of related oncogenes. This study examined the effect of TRAIL, PBOX-15 and the combination on the target genes in prostate cancer cells. Methods RNA was extracted from treated LNCaP cells. cDNA was synthesized, and gene specific primers were subsequently used for amplification in a polymerase chain reaction (PCR) assay. Gene expression was determined using gel electrophoresis and visualised using G:BOX. The intensity of DNA bands for each sample was analysed through gel densitometry. Results c-Myc and BIRC5 expression was detected in the LNCaP cell line following a 24-hour treatment time with each treatment. TRAIL increased expression of c-Myc and BIRC5. In contrast, c-Myc expression was downregulated by PBOX-15, and PBOX-15 in combination with TRAIL showed further decreased of both c-Myc and BIRC5 expression in the LNCaP cell line. Conclusions The presence of c-Myc and BIRC5 in LNCaP cell suggested the potential as therapeutic targets in metastatic prostate cancer. PBOX-15 presented an ability to sensitise cells to the effects of TRAIL, thus provide insight in potential application of the combination for metastatic prostate cancer.
Contamination is a major issue in the biopharmaceutical industry. Bioreactors must be meticulously cleaned to remove residual impurities and avoid cross-contamination. Cleaning validation is necessary to ensure residual contaminants are reduced to the lowest acceptable limits. Bacterial cells represent the paramount challenge in manufacturing equipment cleaning because they are composed of insoluble organic contaminants. Total organic carbon (TOC) analysis is a fast, highly sensitive, and inexpensive analytical technique commonly used to evaluate the approximate level of organic contamination. A study was conducted to assess the effectiveness of cleaning procedures in the removal of contaminants from bioreactor equipment by measuring the TOC concentration of swab samples. A bioreactor was used to obtain a high-density culture of Escherichia coli JM109 cells and a popular enzyme-active anionic detergent was chosen to clean the equipment surfaces. The areas selected for swab sampling included the borosilicate glass vessel and stainless steel impeller blades. The TOC analyzer was calibrated using purified water (blank) and a series of sucrose standard solutions in the range of 1.0 to 100 mg/L. The correlation coefficient (r) was determined to be 0.99911. The limit of detection and limit of quantitation were determined to be 3.46 and 12.89 mg/L, respectively. These results demonstrated that the TOC analyzer was suitable for its intended use. The acceptance limit for the cleaning verification study was calculated to be 7 μg residual matter per cm2 based on a 1 L batch size and a total contact surface area of 1489 cm2. The TOC values obtained for each of the sampled surfaces were significantly above this threshold. Strikingly, the stainless steel blades were found to have the highest levels of contamination with a value of 295 μg/cm2. The high levels of organic contamination were attributed to the enzyme-active anionic detergent that was used during the cleaning procedure. Despite the widespread use of this detergent in the biopharmaceutical industry, there are limited reports describing its use in cleaning validation studies. These findings suggest that this area of research warrants further investigation to ensure that the use of such detergent in bioreactor equipment cleaning does not negatively affect the safety and quality of the subsequent manufactured product. To conclude, the results of this study highlight the importance of cleaning verification, small-scale experimentation, and detergent selection.
Abstract: Existing research demonstrates a lack of data on the relationship between body mass index (BMI) and menopause-related symptoms in postmenopausal women, particularly in Ireland. This study aimed to determine whether there is an association between BMI, general abdominal obesity and menopause-related symptoms in postmenopausal women. This should help bridge the data gap regarding postmenopausal women living in Ireland and their symptoms. Introduction: Menopause is defined as the permanent cessation of a woman's menstrual cycle. This is caused by a reduction of the secretion of oestrogen and progesterone, leading to reduced ovarian function. These changes have been attributed to many psychological, vasomotor and urogenital symptoms such as hot flushes, sleep problems, vaginal dryness, anxiety and exhaustion. Weight gain and body shape changes also occur at this stage of life, although it has not always been directly linked to the menopause. A woman is considered postmenopausal once she has not experienced a period in 12 months. Evidence suggests that there is a potential association between body weight, general abdominal obesity and menopause-related symptoms in postmenopausal women. Methods: This was a cross-sectional study that recruited postmenopausal women. The participants were assessed using validated questionnaires on lifestyle habits and menopausal symptoms using the Menopausal Rating Scale. Participants height, weight and waist circumference were also measured in the health sciences lab on the TUS campus. Results: Of the 26 postmenopausal women, 26.92% (n=7) had a healthy BMI, 38.46% (n=10) were overweight and 34.62% (n=9) were obese. Waist circumference measurements showed that 11.54% (n=3) had a low risk of obesity-related conditions, 7.69% (n=2) were at risk and 80.77% (n=21) were at significant risk. It was found that participants who were obese (10.67±3.80) had significantly higher psychological MRS scores compared to participants who had a healthy BMI (6.57±0.90) (p=0.02). Those women who were meeting the physical activity guidelines were also more likely to report a lower MRS and somatic symptom score (pConclusions: The findings from this study are exploratory but suggest there may be a potential relationship between BMI and psychological menopausal symptoms. Further research in this area using a larger sample size is warranted.
Establishing a model framework for more research necessitates a thorough understanding of the causes, distribution, prevalence, and evolution of infectious illnesses. The main mathematical concept used in this modelling simulation is ordinary differential equations (ODEs). The purpose of this study was to investigate the significance of the many criteria linked to a zombie virus spread. The zombie framework provides an accessible and relatively simple representation of the nature of infectious disease spread, allowing for tractable assumptions and the development of more complex situations. The models are designed around a zombie outbreak in which the zombie virus is spread through a susceptible population. The SIR model developed by Kermack and McKendrick in 1927 as a means of predicting the spread of an infection in a susceptible population is the basic model of choice. The two main methods used in this study are Eulers first order method of solving ordinary differential equations, and the SZR variation of the SIR model, where the Infected class (I) is replaced by the Zombie class (Z). The study showed that without the resurrection mechanism, the classes do not interact with each other and after the resurrection mechanism was included, the susceptible population reduces exponentially upon interaction with infected individuals. Varying parameters were applied to the model, and this resulted in different interactions dependent on the parameter values. The final model included a cure for the zombies, and more susceptible individuals survived proportional to the value assigned to the rate of the spread of the cure. The effect of the difference in parameter values on the amount of time it took for zombies to overtake the susceptible population, with and without a cure were measured using colour coding. Finally, the model design was used to successfully predict the spread of infection of influenza in a boarding school in England in 1978 using the data obtained from the first day of the infection. This model proved efficient in the analysis of different parameters associated with a zombie outbreak even with the inclusion of a cure. The model was even able to be applied to real-world cases as in the 1978 influenza outbreak.
Lipid membranes, which self-assemble in nature and under laboratory conditions, can form vesicles called liposomes. The main uses for liposomes are in drug delivery systems and as animal cell models. From the initial research into lipid membrane science, to the systematic literature review using Web of Science, to refining the project scope, to the description of the method, this project follows the process of developing a method for lipid membrane self-assembly and synthesis in the lab. The result was a rapid prototyping method for fabricating microfluidic devices to test different designs for channels, for use with a liposome synthesis protocol. During development, a simple liposome synthesis protocol was followed, using 1,2 Disteraroyl-sn-glycero-3-phosphocholine (DSPC) to 10 mg/mL in methanol as the lipid solution and 0.9% saline buffer as the aqueous solution. Shrink-plastic (polystyrene) was used as the build material for the microfluidic chip—to construct the design on a larger scale before shrinking to its final size. This method has the advantage of using low cost and easily accessible materials and equipment. Although the development process for this project was at first limited by resource accessibility, this limitation was ultimately embraced. The materials used to fabricate the microfluidic device can be found in craft stores (shrink-plastic sheets), hardware stores (silicone sealant), and aquarium supply stores (thin tubing). During initial prototyping, it is beneficial to quickly fabricate microfluidic devices of different designs. The method developed in this paper lowers the barrier for entry into these preliminary research activities and encourages experimentation.
Multiple Sclerosis is an autoimmune and neurodegenerative disease of the central nervous system. There are currently 2.8 million people living with Multiple Sclerosis worldwide, including 9000 people in Ireland, with a prevalence of 193 per 100,000 people. Symptoms of Multiple Sclerosis include sensory loss, fatigue, cognitive dysfunction, spasticity, depression, optic neuritis, gait ataxia, diplopia, and loss of bladder control. Currently, there is no standardised treatment or cure for Multiple Sclerosis with many strategies focusing on symptoms. Stem cells have emerged as promising approaches for Multiple Sclerosis therapeutics. Clinical trials primarily focus on mesenchymal stem cell-based therapies for Multiple Sclerosis. Furthermore, due to their immunomodulatory and anti-inflammatory characteristics, adipose derived stem cells have recently surfaced as novel therapies for diseases, such as Multiple Sclerosis. Current knowledge shows that there is potential for adipose derived stem cells to replace other adult stem cell-based therapies, as they are much more readily available and involve less invasive isolation procedures. There are currently 371 clinical trials involving mesenchymal stem cells and 462 clinical trials involving adipose derived stem cells, with research focused on skeletal applications, wound healing, and to a lesser degree, haematological and neurological disorders. Although adipose derived stem cells could represent a valuable treatment option for many diseases, several drawbacks to their advancement remain, such as their pro-tumorigenic properties, possible negative alteration of the immune system, and the difficulty in assessing their migration patterns once administered in vivo. Adipose derived stem cell-based therapies have been described as a double-edged sword, with both beneficiary and unfavourable effects observed. Most current clinical trials continue to focus on establishing the safety and efficacy of adipose derived stem cell-based therapeutics, with promising results becoming progressively evident. This review reports stem cell-based therapies as potential therapeutic approaches in the treatment and management of Multiple Sclerosis. This paper explores the characterisation and aetiology of the disease, current treatments for Multiple Sclerosis, and clinical trial data that investigated the therapeutic safety and efficacy of proposed stem cell-derived Multiple Sclerosis treatments.
Introduction: The prevalence of obesity and obesity-related secondary disorders has increased dramatically in recent years. Dysregulated microRNA (miRNA) expression has been linked to the development of obesity and its associated disorders. Adipose derived stem cells (ADSCs) are promising cell models of obesity, obesity-related inflammation and diabetes. Furthermore, miRNA expression profiles have emerged as promising targets for the novel treatment of diseases such as obesity. In order to enhance miRNA-based therapies, the miRNA expression profile of obesity and its related disorders must be monitored to further understand the underlying mechanisms of obesity and to identify novel targets. Aim: The aim of this study was to identify the expression profile of six target miRNAs and three target cytokines. The expression of these targets was compared to control ADSCs, ADSCs differentiated into adipocytes and ADSCs from diabetic patients using a series of tissue culture, molecular biology, and biochemical techniques. This study compares these findings with available literature to identify miRNAs and cytokines that could be novel targets in obesity and diabetes-based therapeutic approaches. Results: The expression of miR-A, miR-221, miR-222, miR-21, miR-146 and miR-133 were significantly dysregulated in obese and diabetic patients compared to controls. MiR-A, a novel miRNA, was identified in this study and was significantly increased in diabetes compared to control samples. Transforming Growth Factor-beta (TGF-β), Tumour Necrosis Factor-alpha (TNF-α) and Vascular Endothelial Growth Factor A (VEGFA) were differentially expressed across each of the cell cohorts investigated. Conclusion: This study identified a novel miRNA and revealed that significant changes in miRNA and cytokine expression have the potential to identify obese patients from diabetic patients. The identification of dysregulated miRNAs and in particular novel dysregulated miRNAs, may lead to the development of miRNA-based personalised therapeutics for obesity and diabetes.
Cancer is a major cause of death worldwide and while chemotherapy is the main approach there are many negative associations in current treatment procedures. These include lack of selectivity, side effects and drug resistance. The hallmarks of cancer are a fundamental concept which aids the development of new means to treat human cancers through the understanding of the acquisition of these hallmarks from cells. Melittin is a major peptide component of bee venom which has shown to be efficacious as an anticancer agent in preclinical and animal models. Melittin has many biological functions including pore formation in the phospholipid bilayer causing cell permeability and lysis. It interacts with various biological signalling pathways which suppress tumour cells, notably, the Hypoxia-Inducible Factor-1, Vascular Endothelial Growth Factor and the Nuclear Factor Kappa B pathways. Despite convincing data presented, its pertinency to human studies has been met with challenges due to non-specific cytotoxicity and haemolytic capabilities. Optimisation techniques for melittin have been developed including the use of gene therapy, co-delivery and nanoparticles. Melittin’s biological functions, the potential methods of delivery and current trends in melittin development for therapy are presented and discussed in this review.
Despite the high mortality rate involved with invasive cerebral mycoses, there is a relative lack of research available around antifungals capable of crossing the blood brain barrier. In this study the metabolites of four plants (Crocus vernus, Miniature Narcissus (daffodil), Osmanthus delavayi and Taraxacum officinale (common dandelion)) and two bacteria (Lacticaseibacillus paracasei and Staphylococcus epidermidis) were extracted and assayed for antifungal activity against Candida albicans and Saccharomyces cerevisiae. Thin layer chromatography and bioautography were then employed to assess the activity of the constituent components of sources showing antifungal activity. Metabolites of S.epidermidis, and extracts of miniature Narcissus and Taraxacum officinal demonstrated no antifungal activity, metabolites of Lacticaseibacillus paracasei demonstrated variable antifungal activity and extracts of Osmanthus delavayi demonstrated previously unreported antifungal activity, although there were issues with repeatability. Osmanthus delavayi warrants further study, with an aim to separate out each component, test it for bioactivity and/or asses for the presence of synergism between two or more components, determine their interactions with the blood brain barrier and any potential toxicities and therefore assess the therapeutic potential.
Background Previous studies have examined the relationship between dietary fibre intake and mood and bowel function separately, however, no cross-sectional study has yet explored the relationship between all three variables. This study examines the association between dietary fibre intake, bowel function and mood in a cohort of Irish adults at a university campus. Methods A cross-sectional study was conducted. An online questionnaire was distributed to staff and students of TU Dublin through email and publicised using posters. Three validated surveys were used in the design of the questionnaire, to assess dietary fibre intake, mood and bowel function. All staff and students of TU Dublin were eligible to participate. Data was collected between the 28th of February and the 13th of March 2023. One-way ANOVA and Independent Samples T-Tests were used to examine the association between the variables and demographic characteristics. Results A total of 275 responses were received. The majority of those who participated were female (69%) and members of the Faculty of Sciences and Health (66.5%). The mean dietary fibre intake of the study cohort was 20.01g/day (SD=11.9g/day). Fifty-four percent of the study cohort reported feeling happy at the time of the questionnaire. A significant association between dietary fibre intake and faculty of study was identified, with those in the Faculty of Sciences and Health having significantly higher intakes than all other faculties (P=0.022). A significant positive association between mean dietary fibre intake and mood status was observed (P=0.009), with those who were happy having a higher mean daily intake of fibre than those who were unhappy and not particularly happy/unhappy (P = 0.039 and P = 0.032, respectively). Significant differences in mood status between each bowel function status were also observed, with those who were happy having significantly better bowel function scores than those who were unhappy and not particularly happy/unhappy (both P < 0.001). Conclusion In this cross-sectional study, dietary fibre intake was found to be largely insufficient amongst Irish adults. Our findings suggest a significant association between both dietary fibre intake and mood and bowel function and mood, however further research is required to elucidate the interplay between all three factors.
Aim: LifeLab is co-designed by and for Junior Cycle students from social disadvantage in Ireland, with the hope to improve health literacy and subsequent health outcomes in this cohort. The aim of this study was to evaluate the enjoyment levels of students participating in the pilot of LifeLab, with a view to informing future development of the intervention. Method: As part of the process evaluation of the pilot of LifeLab, a series of focus groups and purposively designed enjoyment scales were completed by 80 adolescents, from one disadvantaged school in Dublin, Ireland. Inductive thematic analysis was carried out to analyse focus group data, and descriptive analysis of the enjoyment scales was conducted. Findings of the focus groups and enjoyment scales were synthesised and integrated resulting in the generation of a series of higher order and lower order themes of enjoyment. Results: Results of the inductive thematic analysis identified barriers, facilitators and suggestions for increasing enjoyment. Adolescents' enjoyment of the LifeLab intervention can be improved through the integration of fun activity-based learning, competition, variety, and challenge. Conclusions: Findings suggested specific areas of improvement within the intervention, and by using the participant voice, these factors can be incorporated within the LifeLab intervention. It is hoped these refinements, as part of ongoing intervention development, may increase levels of enjoyment, which will therefore enhance the usability and success of LifeLab.
Mitochondria are cytoplasmic, double-membrane organelles that synthesise adenosine triphosphate (ATP). Mitochondria contain their own genome, mitochondrial DNA (mtDNA), which is maternally inherited from the oocyte. Mitochondrial proteins are encoded by either nuclear DNA (nDNA) or mtDNA, and both code for proteins forming the mitochondrial oxidative phosphorylation (OXPHOS) complexes of the respiratory chain. These complexes form a chain that allows the passage of electrons down the electron transport chain (ETC) through a proton motive force, creating ATP from adenosine diphosphate (ADP). This study aims to explore current and prospective therapies for mitochondrial disorders (MTDS). MTDS are clinical syndromes coupled with abnormalities of the ETC and OXPHOS, caused by pathogenic variants in mtDNA or nDNA. Many MTDS emerge from either homoplasmic or heteroplasmic mutations of the DNA, and include mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes. Current therapies include increasing mitochondrial biogenesis, the use of antioxidants, dietary approaches, and exercise. However, these are mostly symptomatic and supportive therapies. Future therapies comprise of personalised and precision medicine approaches which include gene, mitochondrial, cell, and in utero-based therapies. Obstacles towards discovering effective therapies include the rarity of MTDS, its pathogenic complexity and lack of clinical trials. Despite the lack of current curative therapies for MTDS, emerging therapies promise exciting and clinically meaningful therapies in the future.
Previous research has looked at various treatment remedies for improving acute ankle Dorsiflexion Range of Motion (DFROM) post chronic Lateral Ankle Sprain (LAS). Mulligan’s Mobilisation with Movement (MWM) appears frequently however, the significance and mechanism remain quite conflicting (Gilbreath et al., 2015). It is also known that after a LAS, the Lateral Ligament Complex (LLC) is compromised and the calcaneus inverts, increasing stiffness of plantarfascia (Al-Mohrej & Al-Kenani, 2016, Denegar et al., 2002, Loudon & Bell, 1996). The objective of this study was to further explore the effectiveness of MWM compared with soft-tissue (ST) application of the plantarfascia on acute ankle DFROM. 20 male Gaelic footballers (Mean ± SD: Age = 22.5 ± 1.5 years, Ankle DFROM = 29.9⁰ ± 8.6⁰) with a history of chronic LAS (>6-months with no current or recent lower-chain injuries andDFROM) were split into two groups using subject-matching: MWM (n=10), plantarfascia (n=10). The main outcome measure was ankle DFROM using a Weight-Bearing Lunge Test (WBLT) both pre-intervention and immediately post-intervention. There was significant evidence to support the utilisation of either treatment for the improvement of acute ankle DFROM post chronic LAS (P≤0.001). Each group saw increases in ankle DFROM (MWM: 5.6%, plantarfascia: 18.5%) however, there was no statistically significant differences between groups (P≤0.001) and only a small effect size was observed (0.4). These results indicate the clinical relevance of incorporating either treatment intervention into the rehabilitation or treatment protocol of chronic LAS. It would be of interest to view the lasting effects of this study or to view how the treatment interventions may have performed once combined and so future research is recommended for greater comprehension.
