METHODS: Sprague-Dawley rats were divided into four groups: Sham, AMI, AMI treated with PBS (AMI-PBS), and AMI treated with pirfenidone (AMI-PFD) (n=12 each). AMI was induced via coronary artery ligation. The AMI-PFD and AMI-PBS groups received pirfenidone and PBS for 14 days, respectively. Cardiac function, fibrosis, serum cytokines, collagen and elastin content, and their ratios were assessed. Cardiac fibroblasts (CFs) from neonatal rats were categorized into control, hypoxia-induced (LO), LO+PBS, and LO+PFD groups. ELISA measured inflammatory factors, and RT-PCR analyzed collagen and elastin gene expression.
RESULTS: The AMI-PFD group showed improved cardiac function and reduced serum interleukin-1β (IL-1β), IL-6, and transforming growth factor-β (TGF-β). Type I and III collagen decreased by 22.6 % (P=0.0441) and 34.4 % (P=0.0427), respectively, while elastin content increased by 79.4 % (P=0.0126). E/COLI and E/COLIII ratios rose by 81.1 % (P=0.0026) and 88.1 % (P=0.0006). CFs in the LO+PFD group exhibited decreased IL-1β, IL-6, TGF-β, type I and III collagen, with increased elastin mRNA, enhancing the elastin/collagen ratio.
CONCLUSION: Pirfenidone enhances cardiac function by augmenting the early elastin/collagen ratio post-AMI.
OBJECTIVE: This study aimed to compare the difference in cytokine profile between postmenopausal women with and without osteoporosis in Klang Valley, Malaysia.
METHODS: Postmenopausal women with (n = 20) and without osteoporosis (n = 20) were recruited for this study. Their bone health status was determined using dual-energy X-ray absorptiometry. Their fasting blood was collected for proteomic analysis. A protein array was performed for four subjects randomly selected from each group to screen the potential cytokines. Three cytokines at least 20% different between groups and consistently expressed by each subject were selected for validation using enzyme-linked immunosorbent assays (ELISA).
RESULTS: The protein array screening demonstrated that platelet-derived growth factor-BB, interleukin- 6 receptor (IL-6R), and tissue inhibitor of metallopeptidase-2 were higher in women with osteoporosis than women without osteoporosis (n = 4 per group), and consistently expressed by all women. Only body mass index (BMI)-adjusted logarithmically transformed IL-6R levels were lower among postmenopausal women with osteoporosis compared to women with normal bone health (p = 0.026) (n = 16 per group) in the ELISA test.
CONCLUSION: IL-6R was lower among postmenopausal women with osteoporosis compared to women with normal bone health after adjusting for BMI. However, a large-scale epidemiological study with proteomic analysis needs to confirm the findings.
PURPOSE OF REVIEW: Although many therapeutic approaches have been lined up nowadays to treat Diabetes, there are no proper treatment modalities proposed yet in treating diabetic wounds due to the lack of understanding about the role of inflammatory mediators, especially Pro-inflammatory mediators- Cytokines, in the process of Wound healing which we mainly focus on this review.
RECENT FINDINGS: Although complications of Diabetes mellitus are most reported after years of diagnosis, the most severe critical complication is impaired Wound Healing among Diabetes patients. Even though Trauma, Peripheral Artery Disease, and Peripheral Neuropathy are the leading triggering factors for the development of ulcerations, the most significant issue contributing to the development of complicated cutaneous wounds is wound healing impairment. It may even end up with amputation. Newer therapeutic approaches such as incorporating the additives in the present dressing materials, which include antimicrobial molecules and immunomodulatory cytokines is of better therapeutic value.
SUMMARY: The adoption of these technologies and the establishment of novel therapeutic interventions is difficult since there is a gap in terms of a complete understanding of the pathophysiological mechanisms at the cellular and molecular level and the lack of data in terms of the assessment of safety and bioavailability differences in the individuals' patients. The target-specific pro-inflammatory cytokines-based therapies, either by upregulation or downregulation of them, will be helpful in the wound healing process and thereby enhances the Quality of life in patients, which is the goal of drug therapy.
OBJECTIVE: The effects of single targeted 2 Gy and 8 Gy gamma-ray irradiations on the immune cell population (lymphocytes, B-cells, T-cells, neutrophils, eosinophils, and macrophages) in EMT6 mouse-bearing tumour models was investigated.
METHODS: The effects of both irradiation doses in early (96 hours) and acute phase (5 to 11 days) post-irradiation on immune parameters were monitored in blood circulation and TME using flow cytometry. Simultaneously, selected cytokines related to immune cells within the TME were measured using multiplex ELISA.
RESULTS: A temporary reduction in systemic total white blood count (TWBC) resulted from an early phase (96 hours) of gamma-ray irradiation at 2 Gy and 8 Gy compared to sham control group. No difference was obtained in the acute phase. Neutrophils dominated among other immune cells in TME in sham control group. Eosinophils in TME was significantly increased after 8 Gy treatment in acute phase compared to sham control (p< 0.005). Furthermore, the increment of tumour necrosis (TNF)-α, eotaxin and interleukin (IL)-7 (p< 0.05) in both treatment groups and phases were associated with anti-tumour activities within TME by gamma-ray irradiation.
CONCLUSION: The temporary changes in immune cell populations within systemic circulation and TME induced by different doses of gamma-ray irradiation correlated with suppression of several pro-tumorigenic cytokines in mouse-bearing EMT6 tumour models.
METHOD: Prewounded reconstructed full-thickness human skin models were treated with 10µl of either superoxidised solution (Hydrocyn aqua, Bactiguard South East Asia Sdn. Bhd., Malaysia) or Dulbecco's phosphate buffered saline (DPBS) and incubated at 37°C for up to seven days, with additional treatments added every 48 hours. On days 0, 1, 2, 5 and 7, triplicate samples were taken for specific immunostaining against cytokeratin 14 and vimentin. At each timepoint, horizontal and vertical wound diameters were measured to demonstrate wound closure. Maintenance media was taken at the same timepoints for the measurement of secreted proinflammatory cytokines interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-ɑ.
RESULTS: At day 1, the superoxidised solution induced significantly lower diameter measurements compared with baseline data at day 0. Both treatment groups demonstrated significantly lower diameter measurements by day 2 when compared with the baseline; however, the average wound size of samples treated with the superoxidised solution was significantly lower when compared to the DPBS-treated group (p<0.05). No significant difference in expression of any proinflammatory was identified at any timepoint.
CONCLUSION: Application of the superoxidised solution resulted in significantly improved wound closure over the first 48 hours in comparison to DPBS-treatment. Furthermore, application of the superoxidised solution did not induce significant proinflammatory effects, despite the significantly reduced wound diameter.