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European Journal of Endocrinology Jul 2023Adrenal incidentalomas are adrenal masses detected on imaging performed for reasons other than suspected adrenal disease. In most cases, adrenal incidentalomas are...
European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas, in collaboration with the European Network for the Study of Adrenal Tumors.
Adrenal incidentalomas are adrenal masses detected on imaging performed for reasons other than suspected adrenal disease. In most cases, adrenal incidentalomas are nonfunctioning adrenocortical adenomas but may also require therapeutic intervention including that for adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma, or metastases. Here, we provide a revision of the first international, interdisciplinary guidelines on incidentalomas. We followed the Grading of Recommendations Assessment, Development and Evaluation system and updated systematic reviews on 4 predefined clinical questions crucial for the management of incidentalomas: (1) How to assess risk of malignancy?; (2) How to define and manage mild autonomous cortisol secretion?; (3) Who should have surgical treatment and how should it be performed?; and (4) What follow-up is indicated if the adrenal incidentaloma is not surgically removed? Selected Recommendations: (1) Each adrenal mass requires dedicated adrenal imaging. Recent advances now allow discrimination between risk categories: Homogeneous lesions with Hounsfield unit (HU) ≤ 10 on unenhanced CT are benign and do not require any additional imaging independent of size. All other patients should be discussed in a multidisciplinary expert meeting, but only lesions >4 cm that are inhomogeneous or have HU >20 have sufficiently high risk of malignancy that surgery will be the usual management of choice. (2) Every patient needs a thorough clinical and endocrine work-up to exclude hormone excess including the measurement of plasma or urinary metanephrines and a 1-mg overnight dexamethasone suppression test (applying a cutoff value of serum cortisol ≤50 nmol/L [≤1.8 µg/dL]). Recent studies have provided evidence that most patients without clinical signs of overt Cushing's syndrome but serum cortisol levels post dexamethasone >50 nmol/L (>1.8 µg/dL) harbor increased risk of morbidity and mortality. For this condition, we propose the term "mild autonomous cortisol secretion" (MACS). (3) All patients with MACS should be screened for potential cortisol-related comorbidities that are potentially attributably to cortisol (eg, hypertension and type 2 diabetes mellitus), to ensure these are appropriately treated. (4) In patients with MACS who also have relevant comorbidities surgical treatment should be considered in an individualized approach. (5) The appropriateness of surgical intervention should be guided by the likelihood of malignancy, the presence and degree of hormone excess, age, general health, and patient preference. We provide guidance on which surgical approach should be considered for adrenal masses with radiological findings suspicious of malignancy. (6) Surgery is not usually indicated in patients with an asymptomatic, nonfunctioning unilateral adrenal mass and obvious benign features on imaging studies. Furthermore, we offer recommendations for the follow-up of nonoperated patients, management of patients with bilateral incidentalomas, for patients with extra-adrenal malignancy and adrenal masses, and for young and elderly patients with adrenal incidentalomas. Finally, we suggest 10 important research questions for the future.
Topics: Aged; Humans; Adrenal Gland Neoplasms; Dexamethasone; Diabetes Mellitus, Type 2; Hydrocortisone
PubMed: 37318239
DOI: 10.1093/ejendo/lvad066 -
The American Journal of Psychiatry Sep 2023Postpartum depression (PPD) is a common perinatal complication with adverse maternal and infant outcomes. This study investigated the efficacy and safety of zuranolone,... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Postpartum depression (PPD) is a common perinatal complication with adverse maternal and infant outcomes. This study investigated the efficacy and safety of zuranolone, a positive allosteric modulator of synaptic and extrasynaptic GABA receptors and neuroactive steroid, as an oral, once-daily, 14-day treatment course for patients with severe PPD.
METHODS
In this double-blind phase 3 trial, women with severe PPD were randomized in a 1:1 ratio to receive zuranolone 50 mg/day or placebo for 14 days. The primary endpoint was change from baseline in total score on the 17-item Hamilton Depression Rating Scale (HAM-D) at day 15; key secondary endpoints were change from baseline in HAM-D score at days 3, 28, and 45 and change from baseline in Clinical Global Impressions severity (CGI-S) score at day 15. Adverse events were monitored.
RESULTS
Among 196 patients randomized (zuranolone, N=98; placebo, N=98), 170 (86.7%) completed the 45-day study. Treatment with zuranolone compared with placebo resulted in statistically significant improvement in depressive symptoms at day 15 (least squares mean [LSM] change from baseline in HAM-D score, -15.6 vs. -11.6; LSM difference, -4.0, 95% CI=-6.3, -1.7); significant improvement in depressive symptoms was also reported at days 3, 28, and 45. CGI-S score at day 15 significantly improved with zuranolone compared with placebo. The most common adverse events (≥10%) with zuranolone were somnolence, dizziness, and sedation. No loss of consciousness, withdrawal symptoms, or increased suicidal ideation or behavior were observed.
CONCLUSIONS
In this trial, zuranolone demonstrated significant improvements in depressive symptoms and was generally well tolerated, supporting the potential of zuranolone as a novel, rapid-acting oral treatment for PPD.
Topics: Pregnancy; Humans; Female; Depression, Postpartum; Treatment Outcome; Pregnanes; Pyrazoles; Double-Blind Method
PubMed: 37491938
DOI: 10.1176/appi.ajp.20220785 -
Journal of the International Society of... Dec 2023Based on a comprehensive review and critical analysis of the literature regarding the nutritional concerns of female athletes, conducted by experts in the field and... (Review)
Review
Based on a comprehensive review and critical analysis of the literature regarding the nutritional concerns of female athletes, conducted by experts in the field and selected members of the International Society of Sports Nutrition (ISSN), the following conclusions represent the official Position of the Society: 1. Female athletes have unique and unpredictable hormone profiles, which influence their physiology and nutritional needs across their lifespan. To understand how perturbations in these hormones affect the individual, we recommend that female athletes of reproductive age should track their hormonal status (natural, hormone driven) against training and recovery to determine their individual patterns and needs and peri and post-menopausal athletes should track against training and recovery metrics to determine the individuals' unique patterns. 2. The primary nutritional consideration for all athletes, and in particular, female athletes, should be achieving adequate energy intake to meet their energy requirements and to achieve an optimal energy availability (EA); with a focus on the timing of meals in relation to exercise to improve training adaptations, performance, and athlete health. 3. Significant sex differences and sex hormone influences on carbohydrate and lipid metabolism are apparent, therefore we recommend first ensuring athletes meet their carbohydrate needs across all phases of the menstrual cycle. Secondly, tailoring carbohydrate intake to hormonal status with an emphasis on greater carbohydrate intake and availability during the active pill weeks of oral contraceptive users and during the luteal phase of the menstrual cycle where there is a greater effect of sex hormone suppression on gluconogenesis output during exercise. 4. Based upon the limited research available, we recommend that pre-menopausal, eumenorrheic, and oral contraceptives using female athletes should aim to consume a source of high-quality protein as close to beginning and/or after completion of exercise as possible to reduce exercise-induced amino acid oxidative losses and initiate muscle protein remodeling and repair at a dose of 0.32-0.38 g·kg. For eumenorrheic women, ingestion during the luteal phase should aim for the upper end of the range due to the catabolic actions of progesterone and greater need for amino acids. 5. Close to the beginning and/or after completion of exercise, peri- and post-menopausal athletes should aim for a bolus of high EAA-containing (~10 g) intact protein sources or supplements to overcome anabolic resistance. 6. Daily protein intake should fall within the mid- to upper ranges of current sport nutrition guidelines (1.4-2.2 g·kg·day) for women at all stages of menstrual function (pre-, peri-, post-menopausal, and contraceptive users) with protein doses evenly distributed, every 3-4 h, across the day. Eumenorrheic athletes in the luteal phase and peri/post-menopausal athletes, regardless of sport, should aim for the upper end of the range. 7. Female sex hormones affect fluid dynamics and electrolyte handling. A greater predisposition to hyponatremia occurs in times of elevated progesterone, and in menopausal women, who are slower to excrete water. Additionally, females have less absolute and relative fluid available to lose via sweating than males, making the physiological consequences of fluid loss more severe, particularly in the luteal phase. 8. Evidence for sex-specific supplementation is lacking due to the paucity of female-specific research and any differential effects in females. Caffeine, iron, and creatine have the most evidence for use in females. Both iron and creatine are highly efficacious for female athletes. Creatine supplementation of 3 to 5 g per day is recommended for the mechanistic support of creatine supplementation with regard to muscle protein kinetics, growth factors, satellite cells, myogenic transcription factors, glycogen and calcium regulation, oxidative stress, and inflammation. Post-menopausal females benefit from bone health, mental health, and skeletal muscle size and function when consuming higher doses of creatine (0.3 g·kg·d). 9. To foster and promote high-quality research investigations involving female athletes, researchers are first encouraged to stop excluding females unless the primary endpoints are directly influenced by sex-specific mechanisms. In all investigative scenarios, researchers across the globe are encouraged to inquire and report upon more detailed information surrounding the athlete's hormonal status, including menstrual status (days since menses, length of period, duration of cycle, etc.) and/or hormonal contraceptive details and/or menopausal status.
Topics: Female; Humans; Male; Creatine; Progesterone; Athletes; Sports; Amino Acids
PubMed: 37221858
DOI: 10.1080/15502783.2023.2204066 -
The American Journal of Psychiatry Sep 2023This study assessed the efficacy and safety of a 14-day treatment course of once-daily zuranolone 50 mg, an investigational oral positive allosteric modulator of the... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This study assessed the efficacy and safety of a 14-day treatment course of once-daily zuranolone 50 mg, an investigational oral positive allosteric modulator of the γ-aminobutyric acid type A (GABA) receptor, for the treatment of major depressive disorder.
METHODS
Patients 18-64 years of age with severe major depressive disorder were enrolled in this randomized, double-blind, placebo-controlled trial. Patients self-administered zuranolone 50 mg or placebo once daily for 14 days. The primary endpoint was change from baseline in total score on the 17-item Hamilton Depression Rating Scale (HAM-D) at day 15. Safety and tolerability were assessed by incidence of adverse events.
RESULTS
Of 543 randomized patients, 534 (266 in the zuranolone group, 268 in the placebo group) constituted the full analysis set. Compared with patients in the placebo group, patients in the zuranolone group demonstrated a statistically significant improvement in depressive symptoms at day 15 (least squares mean change from baseline HAM-D score, -14.1 vs. -12.3). Numerically greater improvements in depressive symptoms for zuranolone versus placebo were observed by day 3 (least squares mean change from baseline HAM-D score, -9.8 vs. -6.8), which were sustained at all visits throughout the treatment and follow-up periods of the study (through day 42, with the difference remaining nominally significant through day 12). Two patients in each group experienced a serious adverse event; nine patients in the zuranolone group and four in the placebo group discontinued treatment due to adverse events.
CONCLUSIONS
Zuranolone at 50 mg/day elicited a significantly greater improvement in depressive symptoms at day 15, with a rapid time to effect (day 3). Zuranolone was generally well tolerated, with no new safety findings compared with previously studied lower dosages. These findings support the potential of zuranolone in treating adults with major depressive disorder.
Topics: Humans; Adult; Depressive Disorder, Major; Treatment Outcome; Pregnanes; Pyrazoles
PubMed: 37132201
DOI: 10.1176/appi.ajp.20220459 -
JCI Insight Jul 2023The adrenal glands synthesize and release essential steroid hormones such as cortisol and aldosterone, but many aspects of human adrenal gland development are not well...
The adrenal glands synthesize and release essential steroid hormones such as cortisol and aldosterone, but many aspects of human adrenal gland development are not well understood. Here, we combined single-cell and bulk RNA sequencing, spatial transcriptomics, IHC, and micro-focus computed tomography to investigate key aspects of adrenal development in the first 20 weeks of gestation. We demonstrate rapid adrenal growth and vascularization, with more cell division in the outer definitive zone (DZ). Steroidogenic pathways favored androgen synthesis in the central fetal zone, but DZ capacity to synthesize cortisol and aldosterone developed with time. Core transcriptional regulators were identified, with localized expression of HOPX (also known as Hop homeobox/homeobox-only protein) in the DZ. Potential ligand-receptor interactions between mesenchyme and adrenal cortex were seen (e.g., RSPO3/LGR4). Growth-promoting imprinted genes were enriched in the developing cortex (e.g., IGF2, PEG3). These findings reveal aspects of human adrenal development and have clinical implications for understanding primary adrenal insufficiency and related postnatal adrenal disorders, such as adrenal tumor development, steroid disorders, and neonatal stress.
Topics: Infant, Newborn; Humans; Aldosterone; Hydrocortisone; Adrenal Glands; Adrenal Cortex; Steroids; Homeodomain Proteins
PubMed: 37440461
DOI: 10.1172/jci.insight.168177 -
The Cochrane Database of Systematic... Oct 2023Alopecia areata is an autoimmune disease leading to nonscarring hair loss on the scalp or body. There are different treatments including immunosuppressants, hair growth... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alopecia areata is an autoimmune disease leading to nonscarring hair loss on the scalp or body. There are different treatments including immunosuppressants, hair growth stimulants, and contact immunotherapy.
OBJECTIVES
To assess the benefits and harms of the treatments for alopecia areata (AA), alopecia totalis (AT), and alopecia universalis (AU) in children and adults.
SEARCH METHODS
The Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov and WHO ICTRP were searched up to July 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that evaluated classical immunosuppressants, biologics, small molecule inhibitors, contact immunotherapy, hair growth stimulants, and other therapies in paediatric and adult populations with AA.
DATA COLLECTION AND ANALYSIS
We used the standard procedures expected by Cochrane including assessment of risks of bias using RoB2 and the certainty of the evidence using GRADE. The primary outcomes were short-term hair regrowth ≥ 75% (between 12 and 26 weeks of follow-up), and incidence of serious adverse events. The secondary outcomes were long-term hair regrowth ≥ 75% (greater than 26 weeks of follow-up) and health-related quality of life. We could not perform a network meta-analysis as very few trials compared the same treatments. We presented direct comparisons and made a narrative description of the findings.
MAIN RESULTS
We included 63 studies that tested 47 different treatments in 4817 randomised participants. All trials used a parallel-group design except one that used a cross-over design. The mean sample size was 78 participants. All trials recruited outpatients from dermatology clinics. Participants were between 2 and 74 years old. The trials included patients with AA (n = 25), AT (n = 1), AU (n = 1), mixed cases (n = 31), and unclear types of alopecia (n = 4). Thirty-three out of 63 studies (52.3%) reported the proportion of participants achieving short-term hair regrowth ≥ 75% (between 12 and 26 weeks). Forty-seven studies (74.6%) reported serious adverse events and only one study (1.5%) reported health-related quality of life. Five studies (7.9%) reported the proportion of participants with long-term hair regrowth ≥ 75% (greater than 26 weeks). Amongst the variety of interventions found, we prioritised some groups of interventions for their relevance to clinical practice: systemic therapies (classical immunosuppressants, biologics, and small molecule inhibitors), and local therapies (intralesional corticosteroids, topical small molecule inhibitors, contact immunotherapy, hair growth stimulants and cryotherapy). Considering only the prioritised interventions, 14 studies from 12 comparisons reported short-term hair regrowth ≥ 75% and 22 studies from 10 comparisons reported serious adverse events (18 reported zero events and 4 reported at least one). One study (1 comparison) reported quality of life, and two studies (1 comparison) reported long-term hair regrowth ≥ 75%. For the main outcome of short-term hair regrowth ≥ 75%, the evidence is very uncertain about the effect of oral prednisolone or cyclosporine versus placebo (RR 4.68, 95% CI 0.57 to 38.27; 79 participants; 2 studies; very low-certainty evidence), intralesional betamethasone or triamcinolone versus placebo (RR 13.84, 95% CI 0.87 to 219.76; 231 participants; 1 study; very low-certainty evidence), oral ruxolitinib versus oral tofacitinib (RR 1.08, 95% CI 0.77 to 1.52; 80 participants; 1 study; very low-certainty evidence), diphencyprone or squaric acid dibutil ester versus placebo (RR 1.16, 95% CI 0.79 to 1.71; 99 participants; 1 study; very-low-certainty evidence), diphencyprone or squaric acid dibutyl ester versus topical minoxidil (RR 1.16, 95% CI 0.79 to 1.71; 99 participants; 1 study; very low-certainty evidence), diphencyprone plus topical minoxidil versus diphencyprone (RR 0.67, 95% CI 0.13 to 3.44; 30 participants; 1 study; very low-certainty evidence), topical minoxidil 1% and 2% versus placebo (RR 2.31, 95% CI 1.34 to 3.96; 202 participants; 2 studies; very low-certainty evidence) and cryotherapy versus fractional CO2 laser (RR 0.31, 95% CI 0.11 to 0.86; 80 participants; 1 study; very low-certainty evidence). The evidence suggests oral betamethasone may increase short-term hair regrowth ≥ 75% compared to prednisolone or azathioprine (RR 1.67, 95% CI 0.96 to 2.88; 80 participants; 2 studies; low-certainty evidence). There may be little to no difference between subcutaneous dupilumab and placebo in short-term hair regrowth ≥ 75% (RR 3.59, 95% CI 0.19 to 66.22; 60 participants; 1 study; low-certainty evidence) as well as between topical ruxolitinib and placebo (RR 5.00, 95% CI 0.25 to 100.89; 78 participants; 1 study; low-certainty evidence). However, baricitinib results in an increase in short-term hair regrowth ≥ 75% when compared to placebo (RR 7.54, 95% CI 3.90 to 14.58; 1200 participants; 2 studies; high-certainty evidence). For the incidence of serious adverse events, the evidence is very uncertain about the effect of topical ruxolitinib versus placebo (RR 0.33, 95% CI 0.01 to 7.94; 78 participants; 1 study; very low-certainty evidence). Baricitinib and apremilast may result in little to no difference in the incidence of serious adverse events versus placebo (RR 1.47, 95% CI 0.60 to 3.60; 1224 participants; 3 studies; low-certainty evidence). The same result is observed for subcutaneous dupilumab compared to placebo (RR 1.54, 95% CI 0.07 to 36.11; 60 participants; 1 study; low-certainty evidence). For health-related quality of life, the evidence is very uncertain about the effect of oral cyclosporine compared to placebo (MD 0.01, 95% CI -0.04 to 0.07; very low-certainty evidence). Baricitinib results in an increase in long-term hair regrowth ≥ 75% compared to placebo (RR 8.49, 95% CI 4.70 to 15.34; 1200 participants; 2 studies; high-certainty evidence). Regarding the risk of bias, the most relevant issues were the lack of details about randomisation and allocation concealment, the limited efforts to keep patients and assessors unaware of the assigned intervention, and losses to follow-up.
AUTHORS' CONCLUSIONS
We found that treatment with baricitinib results in an increase in short- and long-term hair regrowth compared to placebo. Although we found inconclusive results for the risk of serious adverse effects with baricitinib, the reported small incidence of serious adverse events in the baricitinib arm should be balanced with the expected benefits. We also found that the impact of other treatments on hair regrowth is very uncertain. Evidence for health-related quality of life is still scant.
Topics: Adult; Humans; Child; Child, Preschool; Adolescent; Young Adult; Middle Aged; Aged; Alopecia Areata; Minoxidil; Network Meta-Analysis; Immunosuppressive Agents; Prednisolone; Betamethasone; Cyclosporins; Biological Products
PubMed: 37870096
DOI: 10.1002/14651858.CD013719.pub2 -
Emergency Medicine Clinics of North... Nov 2023The adrenal glands drive physiologic homeostasis, with dysregulation in any direction causing multisystem dysfunction. Adrenal excess states include hyperaldosteronism... (Review)
Review
The adrenal glands drive physiologic homeostasis, with dysregulation in any direction causing multisystem dysfunction. Adrenal excess states include hyperaldosteronism which manifests with refractory hypertension and electrolyte abnormalities including hypernatremia and hypokalemia. Paragangliomas including pheochromocytoma can cause multisystem end-organ dysfunction due to catecholaminergic storm, which require rapid blood pressure control with phentolamine and identification of lesions amenable to surgical resection. Adrenal insufficiency states in contrast can result in hypotension and decompensation refractory to vasopressor administration, requiring adrenal supplementation via hydrocortisone.
Topics: Humans; Emergencies; Hyperaldosteronism; Hydrocortisone; Hypertension; Hypotension
PubMed: 37758424
DOI: 10.1016/j.emc.2023.06.006 -
American Family Physician Sep 2023Primary aldosteronism is the underlying cause of hypertension in primary care settings in approximately 6% of cases, and it is even more common in patients with...
Primary aldosteronism is the underlying cause of hypertension in primary care settings in approximately 6% of cases, and it is even more common in patients with resistant hypertension. However, it is estimated that only about 2% of patients who have risk factors for primary aldosteronism have been formally tested or diagnosed. The first step in the diagnosis of primary aldosteronism is case detection and involves testing patients who are at risk, including individuals with resistant hypertension, as well as those with well-controlled hypertension and a first-degree relative with primary aldosteronism, hypokalemia, an adrenal nodule, atrial fibrillation, obstructive sleep apnea, or a family history of an early stroke (i.e., younger than 40 years). Initial case detection is performed by simultaneously measuring plasma aldosterone concentration and plasma renin activity; an elevated aldosterone-renin ratio (greater than 30) indicates independent aldosterone secretion (i.e., aldosteronism). After a positive case detection, confirmatory testing should be performed. Confirmatory tests include the captopril challenge, oral or intravenous salt loading, or fludrocortisone suppression. Results are positive if aldosterone levels remain high after interventions that suppress or interrupt physiologic production of aldosterone. If the confirmatory test is positive, adrenal computed tomography and adrenal vein sampling should be performed to differentiate unilateral from bilateral adrenal production of aldosterone. Patients with unilateral primary aldosteronism should undergo adrenalectomy, whereas those with bilateral production should be treated with mineralocorticoid receptor antagonists, such as spironolactone or eplerenone.
Topics: Humans; Aldosterone; Renin; Hypertension; Spironolactone; Hyperaldosteronism
PubMed: 37725461
DOI: No ID Found -
Cells Nov 2023Cortisol, a critical glucocorticoid hormone produced by the adrenal glands, plays a pivotal role in various physiological processes. Its release is finely orchestrated... (Review)
Review
Cortisol, a critical glucocorticoid hormone produced by the adrenal glands, plays a pivotal role in various physiological processes. Its release is finely orchestrated by the suprachiasmatic nucleus, governing the circadian rhythm and activating the intricate hypothalamic-pituitary-adrenal (HPA) axis, a vital neuroendocrine system responsible for stress response and maintaining homeostasis. Disruptions in cortisol regulation due to chronic stress, disease, and aging have profound implications for multiple bodily systems. Animal models have been instrumental in elucidating these complex cortisol dynamics during stress, shedding light on the interplay between physiological, neuroendocrine, and immune factors in the stress response. These models have also revealed the impact of various stressors, including social hierarchies, highlighting the role of social factors in cortisol regulation. Moreover, chronic stress is closely linked to the progression of neurodegenerative diseases, like Alzheimer's and Parkinson's, driven by excessive cortisol production and HPA axis dysregulation, along with neuroinflammation in the central nervous system. The relationship between cortisol dysregulation and major depressive disorder is complex, characterized by HPA axis hyperactivity and chronic inflammation. Lastly, chronic pain is associated with abnormal cortisol patterns that heighten pain sensitivity and susceptibility. Understanding these multifaceted mechanisms and their effects is essential, as they offer insights into potential interventions to mitigate the detrimental consequences of chronic stress and cortisol dysregulation in these conditions.
Topics: Animals; Hydrocortisone; Depressive Disorder, Major; Neurodegenerative Diseases; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System
PubMed: 38067154
DOI: 10.3390/cells12232726 -
ACS Nano Nov 2023Spinal cord injury (SCI) can cause permanent loss of sensory and motor function, and there is no effective clinical treatment, to date. Due to the complex pathological...
Spinal cord injury (SCI) can cause permanent loss of sensory and motor function, and there is no effective clinical treatment, to date. Due to the complex pathological process involved after injury, synergistic treatments are very urgently needed in clinical practice. We designed a nanofiber scaffold hyaluronic acid hydrogel patch to release both exosomes and methylprednisolone to the injured spinal cord in a non-invasive manner. This composite patch showed good biocompatibility in the stabilization of exosome morphology and toxicity to nerve cells. Meanwhile, the composite patch increased the proportion of M2-type macrophages and reduced neuronal apoptosis in an in vitro study. In vivo, the functional and electrophysiological performance of rats with SCI was significantly improved when the composite patch covered the surface of the hematoma. The composite patch inhibited the inflammatory response through macrophage polarization from M1 type to M2 type and increased the survival of neurons by inhibition neuronal of apoptosis after SCI. The therapeutic effects of this composite patch can be attributed to TLR4/NF-κB, MAPK, and Akt/mTOR pathways. Thus, the composite patch provides a medicine-exosomes dual-release system and may provide a non-invasive method for clinical treatment for individuals with SCI.
Topics: Rats; Animals; Methylprednisolone; Exosomes; Spinal Cord Injuries; Macrophages; Neurons; Spinal Cord
PubMed: 37948097
DOI: 10.1021/acsnano.3c08046