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Background Numerous experimental models have shown that microRNAs (miRNAs)play an important role in regulating pain processing in clinical pain disorders. In this study, we evaluated a set of miRNAs as diagnostic biomarkers of pain intensity in adolescents with chronic fatigue syndrome (CFS). We then correlated the expression of these miRNAs with the levels of inflammatory markers and pain‐related comorbidities in adolescents with CFS and healthy controls (HCs). Methods A total of 150 adolescents, 12 to 18 years of age, participated in this study between April 2016 and April 2017. The participants were classified into 2 groups: adolescents with CFS (n = 100) and HCs (n = 50). Reverse‐transcription polymerase chain reaction was used to evaluate the expression of miR‐558, miR‐146a, miR‐150, miR‐124, and miR‐143. Immunoassay analysis was used to assess the levels of immune inflammatory markers interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), and cyclooxygenase‐2 (COX‐2). Results Adolescents with CFS showed significantly higher pain thresholds than comparable nonfatigued HCs. Ability to enjoy life and relations with others were the parameters least influenced by pain in CFS patients. Differential expression of miR‐558, miR‐146a, miR‐150, miR‐124, and miR‐143 was significantly downregulated and notably interfered with pain intensity and frequency in patients with CFS. Also, the expression of these miRNAs was significantly correlated with that of IL‐6, TNF‐α, and COX‐2, which have been shown to mediate pain intensity in patients with CFS. Girls with CFS showed significantly decreased expression levels of these miRNAs compared with the levels of boys with CFS. Girls with CFS also showed increased expression of the inflammatory pain–related markers IL‐6, TNF‐α, and COX‐2 compared with the levels of boys with CFS. Conclusions The intensity and consequences of pain were influenced by differential expression of miR‐558, miR‐146a, miR‐150, miR‐124, and miR‐143, which was directly associated with higher expression of the immune inflammatory‐related genes TNFα, IL‐6, and COX‐2 in adolescents with CFS. Further studies of larger patient cohorts will help clarify the role of miRNAs in the pathogenesis of CFS.

Green tea (Camellia sinensis) has many biological activities and may promote diabetic wound healing by regulation of circulating hypoxia responsive microRNAs (HRMs) which triggers the wound repairing process in diabetic and nondiabetic wounds. Thus, in this study, the potential effects of green tea extract (GTE) on the expression of miRNAs; miR-424, miR-199a, miR-210, miR-21, and fibrogenitic markers; hydroxyproline (HPX), fibronectin (FN), and nitric oxide (NO) were evaluated in wounds of diabetic and nondiabetic rats. The animals were topically treated with vaseline, 0.6% GTE, and 5%w/w povidone iodine (standard control). HPX, FN, and NO levels and microRNAs, miR-424, miR-210, miR-199a, and miR-21, were estimated in wound tissues using colorimetric, immunoassay, and molecular PCR analysis. In vitro analysis was performed to estimate active constituents and their antioxidant activities in methanolic green teat extract (GTE). Wounds treated with green tea, a dose of 0.6, healed significantly earlier than those treated with standard vehicle and vaseline treated diabetic wounds. Higher expressions of HRMs, miR-199a, and miR-21, and lower expression of HRMs, miR-424 and miR-210, were significantly reported in tissues following treatment with green tea extract compared to standard control vehicle. The tissues also contained more collagen expressed as measures of HPX, FN, and NO and more angiogenesis, compared to wounds treated with standard control vehicle. Diabetic and nondiabetic wounds treated with green tea (0.6%) for three weeks had lesser scar width and greater re-epithelialization in shorter periods when compared to standard control vehicle. Expression of HRMs, miR-199a, miR-21, and HRMs and miR-424 and miR-210 correlated positively with HPX, fibronectin, NO, better scar formation, and tensile strength and negatively with diabetes. In addition to antidiabetic and antioxidant activities of green tea components, GTE showed angiogenesis promoting activity in diabetic wound healing. In conclusion, Camellia sinensis extracts in a dose of 0.6% significantly promote more collagen and fibronectin deposition with higher expression of NO, promoting angiogenesis process via molecular controlling of circulating hypoxia responsive microRNAs: miR-424, miR-210, miR-199a, and miR-21 in diabetic and nondiabetic wounds. Our results support a functional role of circulating hypoxia responsive microRNAs: miR-424, miR-210, miR-199a, and miR-21 as potential therapeutic targets in angiogenesis and vascular remodeling in diabetic wound healing.

Background. MicroRNAs (miRNA) identified as critical molecular regulators for bone development, function, and modeling/remodeling process and could be predictable for osteoporotic fractures in postmenopausal elderly women. Aim. The potential diagnostic role of circulating miRNAs, miR-148a and miR-122-5p, in the pathogenesis of osteoporosis and its association with bone markers, hypercortisolism, and vitamin D deficiency were explored in postmenopausal elderly women with osteoporosis. Methods. A total of 120 elderly women aged 50–80 years old were recruited in this study, of which only 100 eligible women with amenorrhea of at least 12 consecutive months or surgical menopause participated in this study. Based upon bone mineral density (BMD) measurements, the participants were classified according into two groups: normal ( n = 45 ; T score of ≥-1.0) and osteoporosis ( n = 55 ; T score: ≤-2.5). Circulating miRNAs, miR-148a and miR-122-5p, were estimated by real-time RT-PCR analysis. In addition, bone markers, hypercortisolism, and vitamin D deficiency were colorimetrically and ELISA immune assay estimated. The potential role of miR-148a, miR-122-5p, cortisol, and vitamin D in the diagnosis of osteoporosis was predicted using the analysis of the respective area under the receiver operating characteristic curve (AUC-ROC). Results. The expressed level of miR-148a significantly increased and miR-122-5p significantly decreased in the serum of osteoporotic patients compared to healthy controls. In addition, a significant increase in the levels of cortisol, s-BAP, and CTx and significant decrease in the levels of T-BMD, the levels of OC, and s-Ca were also identified. All parameters significantly correlated with fracture risk parameters; BMD, and T score lumbar spine (L2-L4). Thus, the data showed AUC cut off values (miR-148a; 0.876, miR-122-5p; 0.761) were best evaluated for clinical diagnosis of patients with osteoporosis and that AUC cut off values of 0.748 for cortisol and 0.635 for vitamin D were the best cut off values, respectively, reported for the prediction of osteoporosis clinical diagnosis. Conclusion. In this study, expressed miRNAs miR-148a and miR-122-5p and changes in the levels of both cortisol and vitamin D status are significantly associated with bone loss or osteoporosis. Thus, circulation miRNAs alone or in combination with cortisol and vitamin D status might be considered predictable biomarkers in the diagnosis or the pathogenesis of osteoporosis in elderly postmenopausal women; however, more studies are recommended.

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