Dysregulated brain-gut axis in the setting of traumatic brain injury: review of mechanisms and anti-inflammatory pharmacotherapies

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: May 10, 2024

Abstract Traumatic brain injury (TBI) is a chronic and debilitating disease, associated with high risk of psychiatric neurodegenerative diseases. Despite significant advancements in improving outcomes, the lack effective treatments underscore urgent need for innovative therapeutic strategies. The brain-gut axis has emerged as crucial bidirectional pathway connecting gastrointestinal (GI) system through an intricate network neuronal, hormonal, immunological pathways. Four main pathways are primarily implicated this crosstalk, including systemic immune system, autonomic enteric nervous systems, neuroendocrine microbiome. TBI induces profound changes gut, initiating unrestrained vicious cycle that exacerbates axis. Alterations gut include mucosal damage malabsorption nutrients/electrolytes, disintegration intestinal barrier, increased infiltration cells, dysmotility, dysbiosis, enteroendocrine cell (EEC) dysfunction disruption (ENS) (ANS). Collectively, these further contribute to neuroinflammation neurodegeneration via gut-brain In review article, we elucidate roles various anti-inflammatory pharmacotherapies capable attenuating dysregulated inflammatory response along TBI. These agents hormones such serotonin, ghrelin, progesterone, ANS regulators beta-blockers, lipid-lowering drugs like statins, flora modulators probiotics antibiotics. They attenuate by targeting distinct both post-TBI. exhibit promising potential mitigating inflammation enhancing neurocognitive outcomes patients.

Language: Английский

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Exploring the Complexities of Long COVID

Viruses, Journal Year: 2024, Volume and Issue: 16(7), P. 1060 - 1060

Published: June 30, 2024

Since the emergence of SARS-CoV-2 virus in 2019, nearly 700 million COVID-19 cases and 7 deaths have been reported globally. Despite most individuals recovering within four weeks, Center for Disease Control (CDC) estimates that 7.5% to 41% develop post-acute infection syndrome (PAIS), known as 'Long COVID'. This review provides current statistics on Long COVID's prevalence, explores hypotheses concerning epidemiological factors, such age, gender, comorbidities, initial severity, vaccine interactions, delves into potential mechanisms, including immune responses, viral persistence, gut dysbiosis. Moreover, we conclude women, advanced non-vaccination, low socioeconomic status all appear be risk factors. The reasons these differences are still not fully understood likely involve a complex relationship between social, genetic, hormonal, other Furthermore, with seem more endure economic hardship due persistent symptoms. In summary, our findings further illustrate multifaceted nature COVID underscore importance understanding factors mechanisms needed effective therapeutic strategies interventions.

Language: Английский

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Graphene oxide quantum dots-loaded sinomenine hydrochloride nanocomplexes for effective treatment of rheumatoid arthritis via inducing macrophage repolarization and arresting abnormal proliferation of fibroblast-like synoviocytes

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: July 1, 2024

The characteristic features of the rheumatoid arthritis (RA) microenvironment are synovial inflammation and hyperplasia. Therefore, there is a growing interest in developing suitable therapeutic strategy for RA that targets macrophages fibroblast-like synoviocytes (FLSs). In this study, we used graphene oxide quantum dots (GOQDs) loading anti-arthritic sinomenine hydrochloride (SIN). By combining with hyaluronic acid (HA)-inserted hybrid membrane (RFM), successfully constructed new nanodrug system named HA@RFM@GP@SIN NPs target therapy inflammatory articular lesions. Mechanistic studies showed nanomedicine was effective against by facilitating transition M1 to M2 inhibiting abnormal proliferation FLSs vitro. vivo potential investigation demonstrated its effects on macrophage polarization hyperplasia, ultimately preventing cartilage destruction bone erosion preclinical models adjuvant-induced collagen-induced rats. Metabolomics indicated were mainly associated regulation steroid hormone biosynthesis, ovarian steroidogenesis, tryptophan metabolism, tyrosine metabolism. More notably, transcriptomic analyses revealed suppressed cell cycle pathway while inducing apoptosis pathway. Furthermore, protein validation disrupted excessive growth RAFLS interfering PI3K/Akt/SGK/FoxO signaling cascade, resulting decline cyclin B1 expression arrest G2 phase. Additionally, considering favorable biocompatibility biosafety, these multifunctional nanoparticles offer promising approach patients RA.

Language: Английский

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T cells in obesity‐associated inflammation: The devil is in the details

Immunological Reviews, Journal Year: 2024, Volume and Issue: 324(1), P. 25 - 41

Published: May 20, 2024

Summary Obesity presents a significant health challenge, affecting 41% of adults and 19.7% children in the United States. One associated challenges obesity is chronic low‐grade inflammation. In both mice humans, T cells circulation adipose tissue play pivotal role obesity‐associated Changes numbers frequency specific CD4 + Th subsets their contribution to inflammation through cytokine production indicate declining metabolic health, that is, insulin resistance T2D. While some subset alterations are consistent between humans with obesity, changes mainly characterize male mice, whereas female often resist However, protection from not observed human females, who can develop obesity‐related T‐cell akin males. The decline sex hormones after menopause also implicated promoting Age second underappreciated factor for defining regulating toward translating basic science findings clinic. Weight loss parallel these other factors, does resolve Instead, persists amid modest cell frequencies, highlighting need further research into resolving function weight loss. How lingering common struggle maintain lower unknown. Semaglutide, newly popular pharmaceutical used treating T2D reversing holds promise alleviating complications, yet its impact on T‐cell‐mediated remains unexplored. Further work this area could significantly contribute scientific understanding impacts sex/hormones decline.

Language: Английский

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A unified model of the biology of peripartum depression

Translational Psychiatry, Journal Year: 2023, Volume and Issue: 13(1)

Published: April 28, 2023

Abstract Peripartum depression (PPD) is a prevalent and debilitating disorder that adversely affects the development of mothers infants. Recently, there has been plea for increased mental health screening during peripartum period; however, currently, no accurate tool to identify women at risk PPD. In addition, some do not respond current treatment schemes develop treatment-resistant depression. The perspective aims propose unified understanding biological underpinnings PPD (UmPPD) considers heterogeneity in onset, symptoms cluster, severity Such model could promote basic applied research on suggest new avenues. central hub kynurenine pathway (KP) KP-serotonin ratio. forces specific processes play cause an imbalance within KP between serotonin are inflammation, stress, reproductive hormones (especially estradiol progesterone), oxytocin. UmPPD predicts most severe would comprise prolonged ongoing or multiple stressors, excessive estrogen, progesterone resistance, avoidance breastfeeding, skin-to-skin contact, social proximity. These factors be associated with higher likelihood developing PPD, early more significant symptom severity. subtypes consist different compositions expressions these components, one common factor. aid directing future possibly detecting critical help discover, develop, utilize novel treatments

Language: Английский

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Proposal for targeted, neo-evolutionary-oriented secondary prevention of early-onset endometriosis and adenomyosis. Part II: medical interventions

Human Reproduction, Journal Year: 2023, Volume and Issue: 39(1), P. 18 - 34

Published: Nov. 10, 2023

According to consistent epidemiological data, the slope of incidence curve endometriosis rises rapidly and sharply around age 25 years. The delay in diagnosis is generally reported be between 5 8 years adult women, but it appears over 10 adolescents. If this true, actual onset many young women would chronologically placed early postmenarchal Ovulation menstruation are inflammatory events that, when occurring repeatedly for years, may theoretically favour development adenomyosis. Moreover, repeated acute dysmenorrhoea episodes after menarche not only an indicator ensuing or adenomyosis, also promote transition from chronic pelvic pain through central sensitization mechanisms, as well overlapping conditions. Therefore, secondary prevention aimed at reducing suffering, limiting lesion progression, preserving future reproductive potential should focused on group that could benefit most intervention, i.e. severely symptomatic Early-onset adenomyosis promptly suspected even physical ultrasound findings negative, long-term ovulatory suppression established until conception seeking. As nowadays mean using hormonal therapies several drug safety evaluation crucial. In adolescents without recognized major contraindications oestrogens, use very low-dose combined oral contraceptives associated with a marginal increase individual absolute risk thromboembolic events. Oral containing oestradiol instead ethinyl further limit such risk. Oral, subcutaneous, intramuscular progestogens do risk, interfere attainment peak bone mass women. Levonorgestrel-releasing intra-uterine devices safe alternative adolescents, amenorrhoea frequently induced ovarian activity. With regard oncological net effect oestrogen-progestogen combinations small reduction overall cancer Whether surgery considered first-line approach symptoms seems questionable. Especially large endometriomas infiltrating lesions detected imaging, laparoscopy reserved who refuse treatments whom medications effective, tolerated, contraindicated. Diagnostic therapeutic algorithms, including self-reported outcome measures, individuals clinical suspicion early-onset proposed.

Language: Английский

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Neuroactive Steroids, Toll-like Receptors, and Neuroimmune Regulation: Insights into Their Impact on Neuropsychiatric Disorders

Life, Journal Year: 2024, Volume and Issue: 14(5), P. 582 - 582

Published: April 30, 2024

Pregnane neuroactive steroids, notably allopregnanolone and pregnenolone, exhibit efficacy in mitigating inflammatory signals triggered by toll-like receptor (TLR) activation, thus attenuating the production of factors. Clinical studies highlight their therapeutic potential, particularly conditions like postpartum depression (PPD), where FDA-approved compound brexanolone, an intravenous formulation allopregnanolone, effectively suppresses TLR-mediated pathways, predicting symptom improvement. Additionally, pregnane neurosteroids trophic anti-inflammatory properties, stimulating vital proteins Androstane including estrogens androgens, along with dehydroepiandrosterone (DHEA), display diverse effects on TLR expression activation. Notably, androstenediol (ADIOL), androstane neurosteroid, emerges as a potent agent, promising for interventions. The dysregulation immune responses via signaling alongside reduced levels endogenous significantly contributes to severity across various neuropsychiatric disorders. Neuroactive such demonstrate alleviating symptoms disorders modulating neuroimmune responses, offering potential intervention avenues. This review emphasizes significant steroids addressing processes associated It advances our understanding complex interplay between paving way personalized treatment strategies tailored individual needs providing insights future research aimed at unraveling intricacies

Language: Английский

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Downregulation of pattern recognition receptors on macrophages involved in aggravation of endometriosis

American Journal of Reproductive Immunology, Journal Year: 2024, Volume and Issue: 91(1)

Published: Jan. 1, 2024

Abstract Problem In women of reproductive age, endometriosis may contribute to dysmenorrhea, chronic pelvic pain, dyspareunia, infertility, adenomyosis, and endometrial ovarian cyst (EOC). Recent studies have shown that inflammation occurs in the pelvis patients this is exacerbated by immunosuppression, leading survival debris. However, detailed immunological mechanisms underlying aggravation immunosuppression remain unclear. Method Study We investigate alarmins (high‐mobility group box‐1, IL‐33, IL‐1α, S100B protein), proinflammatory cytokines (IL‐6 IL‐1β), immune cells (CD8 + T cells, CD4 natural killer dendritic macrophages) peritoneal fluid with EOC using enzyme‐linked immunosorbent assay, electrochemiluminescence, flow cytometry. Then, we analyzed correlation between these factors aggravating indicators endometriosis, tumor size revised American Society for Reproductive Medicine (r‐ASRM) score. Results Unexpectedly, there was no each alarmin level indicators. expression pattern recognition receptors, toll‐like receptor 4, advanced glycation end‐products on macrophages inversely correlated Conclusions The associated a decrease receptors but not levels. Investigation innate systems, such as their help elucidate new endometriosis.

Language: Английский

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Sex‐dependent improvement in traumatic brain injury outcomes after liposomal delivery of dexamethasone in mice

Bioengineering & Translational Medicine, Journal Year: 2024, Volume and Issue: 9(4)

Published: Feb. 4, 2024

Abstract Traumatic brain injury (TBI) can have long‐lasting physical, emotional, and cognitive consequences due to the neurodegeneration caused by its robust inflammatory response. Despite advances in rehabilitation care, effective neuroprotective treatments for TBI patients are lacking. Furthermore, current drug delivery methods treatment inefficient targeting inflamed areas. To address this issue, we developed a liposomal nanocarrier (Lipo) encapsulating dexamethasone (Dex), an agonist glucocorticoid receptor utilized alleviate inflammation swelling various conditions. In vitro studies show that Lipo‐Dex were well tolerated human murine neural cells. showed significant suppression of cytokines, IL‐6 TNF‐α, release after induction with lipopolysaccharide. Further, administered young adult male female C57BL/6 mice immediately controlled cortical impact (a model). Our findings demonstrate selectively target injured brain, thereby reducing lesion volume, cell death, astrogliosis, pro‐inflammatory microglial activation compared Lipo‐treated sex‐dependent manner, showing major only mice. This highlights importance considering sex as crucial variable developing evaluating new nano‐therapies injury. These results suggest administration may effectively treat acute TBI.

Language: Английский

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Effects of COVID-19 Infection and Vaccination on the Female Reproductive System: A Narrative Review

Balkan Medical Journal, Journal Year: 2023, Volume and Issue: 40(3), P. 153 - 164

Published: April 28, 2023

Several studies and research papers have been published to elucidate understand the mechanism of coronavirus disease 2019 (COVID-19) pandemic its long-term effects on human body. COVID-19 affects a number organs, including female reproductive system. However, less attention has given system due their low morbidity. The results investigating relationship between infection ovarian function in women age shown harmless involvement infection. reported oocyte quality, function, dysfunctions uterine endometrium menstrual cycle. findings these indicate that negatively follicular microenvironment dysregulate function. Although health studied humans animals, very few examined how objective this review is summarize current literature categorize system, ovaries, uterus, hormonal profiles. maturation, oxidative stress, which causes chromosomal instability apoptosis vitro fertilization cycle, high-quality embryos, premature insufficiency, vein thrombosis, hypercoagulable state, women’s hypothalamus-pituitary-ovary axis, sex hormones, estrogen, progesterone, anti-Müllerian hormone, are discussed particular.

Language: Английский

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