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Biomedicine & Pharmacotherapy =... Dec 2023Deep Brain Stimulation (DBS) and Spinal Cord Stimulation (SCS) represent burgeoning treatments for diverse neurological disorders. This systematic review aims to... (Review)
Review
INTRODUCTION
Deep Brain Stimulation (DBS) and Spinal Cord Stimulation (SCS) represent burgeoning treatments for diverse neurological disorders. This systematic review aims to consolidate findings on the immunological and endocrine effects of DBS and SCS, shedding light on the intricate mechanisms of neuromodulation.
MATERIALS AND METHODS
This systematic review, aligned with PRISMA protocols, synthesizes findings from 33 references-20 on DBS and 13 on SCS-to unravel the immunological and endocrine impacts of neuromodulation.
RESULTS
DBS interventions exhibited divergent effects on cytokines, with an increase in hepcidin levels and a variable impact on the IL-6/IL-10 ratio. While some studies reported elevated IL-6, animal studies consistently demonstrated a reduction in IL-1β and IL-6, with no significant changes in TNF-α and an increase in IL-10. Noteworthy hormonal changes included decreased corticosterone and ACTH concentrations and increased oxytocin levels following DBS of the hypothalamus. SCS mirrored similar effects on interleukins, indicating a reduction in IL-6 and IL-1β and an increase in IL-10 levels. Additionally, SCS led to reduced VEGF levels and elevated expression of neurotrophic factors such as BDNF and GDNF, particularly under burst stimulation.
CONCLUSIONS
Both DBS and SCS exert anti-inflammatory effects, manifesting as a decrease in pro-inflammatory cytokines alongside the stimulation of anti-inflammatory cytokine synthesis. These findings, observed in both animal and human models, imply that neurostimulation may modify the trajectory of neurological diseases by modulating local immune responses in an immunomodulatory and endocrine manner. This comprehensive exploration sets the stage for future research endeavors in this evolving domain.
Topics: Animals; Humans; Interleukin-10; Spinal Cord Stimulation; Deep Brain Stimulation; Interleukin-6; Vascular Endothelial Growth Factor A; Cytokines; Immunity; Anti-Inflammatory Agents; Spinal Cord
PubMed: 37862972
DOI: 10.1016/j.biopha.2023.115732 -
Diabetes, Obesity & Metabolism Dec 2023To summarize the evidence of recently published randomized controlled trials (RCTs) studying efficacy, in terms of glycaemic control, and safety of the newly developed... (Meta-Analysis)
Meta-Analysis
AIM
To summarize the evidence of recently published randomized controlled trials (RCTs) studying efficacy, in terms of glycaemic control, and safety of the newly developed once-weekly basal insulin analogues.
METHODS
A systematic literature search was conducted through Medline (via PubMed), Cochrane Library and Google Scholar until June 30, 2023. Double-independent study selection, data extraction and quality assessment were performed. Results were summarized with random-effects meta-analysis.
RESULTS
A total of 3962 patients with type 2 diabetes mellitus (T2DM) among nine RCTs were analysed. All RCTs had low risk of bias according to the Cochrane Collaboration risk-of-bias tool (RoB2). Once-weekly insulins demonstrated better efficacy in glycated haemoglobin (HbA1c) reduction (mean difference [MD] -0.13%, 95% confidence interval [CI] -0.23, -0.03; P = 0.08) and a significantly greater time in range compared with once-daily insulin analogues (MD 3.54%, 95% CI 1.56, 5.53; P = 0.005). Based on subgroup analyses, the reduction in HbA1c and the odds of achieving an end-of-treatment HbA1c <6.5% were significantly greater for icodec compared to the once-daily insulin (MD -0.18%, 95% CI -0.27, -0.09 [P < 0.001] and odds ratio [OR] 1.75, 95% CI 1.34, 2.29 [P < 0.001], respectively). Once-weekly insulins were associated with higher odds of level 1 hypoglycaemia during the 24-hour period (OR 1.3, 95% CI 1.04, 1.64; P = 0.02) but were safer in terms of level 2 or 3 nocturnal hypoglycaemic events (OR 0.74, 95% CI 0.56, 0.97; P = 0.03). No difference was observed regarding serious adverse events between the two groups.
CONCLUSION
The once-weekly basal insulin analogues seem to be at least equally efficient in glycaemic management and safe compared to once-daily injections in people with T2DM. Phase 4 RCTs are expected to shed further light on the effectiveness and safety of once-weekly insulin therapy over the long term.
Topics: Humans; Insulin; Glycated Hemoglobin; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Hypoglycemia; Insulin, Regular, Human
PubMed: 37667676
DOI: 10.1111/dom.15259 -
Cytokine Sep 2023Biliary tract cancer (BTC) is a highly malignant tumor that originates from bile duct epithelium and is categorized into intrahepatic cholangiocarcinoma (iCCA),... (Review)
Review
Biliary tract cancer (BTC) is a highly malignant tumor that originates from bile duct epithelium and is categorized into intrahepatic cholangiocarcinoma (iCCA), perihilar cholangiocarcinoma (pCCA), distal cholangiocarcinoma (dCCA) and gallbladder cancer (GBC) according to the anatomic location. Inflammatory cytokines generated by chronic infection led to an inflammatory microenvironment which influences the carcinogenesis of BTC. Interleukin-6 (IL-6), a multifunctional cytokine secreted by kupffer cells, tumor-associated macrophages, cancer-associated fibroblasts (CAFs) and cancer cells, plays a central role in tumorigenesis, angiogenesis, proliferation, and metastasis in BTC. Besides, IL-6 serves as a clinical biomarker for diagnosis, prognosis, and monitoring for BTC. Moreover, preclinical evidence indicates that IL-6 antibodies could sensitize tumor immune checkpoint inhibitors (ICIs) by altering the number of infiltrating immune cells and regulating the expression of immune checkpoints in the tumor microenvironment (TME). Recently, IL-6 has been shown to induce programmed death ligand 1 (PD-L1) expression through the mTOR pathway in iCCA. However, the evidence is insufficient to conclude that IL-6 antibodies could boost the immune responses and potentially overcome the resistance to ICIs for BTC. Here, we systematically review the central role of IL-6 in BTC and summarize the potential mechanisms underlying the improved efficacy of treatments combining IL-6 antibodies with ICIs in tumors. Given this, a future direction is proposed for BTC to increase ICIs sensitivity by blocking IL-6 pathways.
Topics: Humans; Interleukin-6; Biliary Tract Neoplasms; Cholangiocarcinoma; Cytokines; Antibodies; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Tumor Microenvironment
PubMed: 37331095
DOI: 10.1016/j.cyto.2023.156271 -
Military Medical Research Oct 2023Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations,...
BACKGROUND
Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations, such as firefighting, law enforcement, military, and sports. A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work environment.
METHODS
To study regulatory processes in intense physical activity simulating real-life conditions, we performed a multi-omics analysis of three biofluids (blood plasma, urine, and saliva) collected from 11 wildland firefighters before and after a 45 min, intense exercise regimen. Omics profiles post- versus pre-exercise were compared by Student's t-test followed by pathway analysis and comparison between the different omics modalities.
RESULTS
Our multi-omics analysis identified and quantified 3835 proteins, 730 lipids and 182 metabolites combining the 3 different types of samples. The blood plasma analysis revealed signatures of tissue damage and acute repair response accompanied by enhanced carbon metabolism to meet energy demands. The urine analysis showed a strong, concomitant regulation of 6 out of 8 identified proteins from the renin-angiotensin system supporting increased excretion of catabolites, reabsorption of nutrients and maintenance of fluid balance. In saliva, we observed a decrease in 3 pro-inflammatory cytokines and an increase in 8 antimicrobial peptides. A systematic literature review identified 6 papers that support an altered susceptibility to respiratory infection.
CONCLUSION
This study shows simultaneous regulatory signatures in biofluids indicative of homeostatic maintenance during intense physical activity with possible effects on increased infection susceptibility, suggesting that caution against respiratory diseases could benefit workers on highly physical demanding jobs.
Topics: Humans; Multiomics; Exercise; Cytokines
PubMed: 37853489
DOI: 10.1186/s40779-023-00477-5 -
Nutrition Journal Oct 2023The present systematic review and meta-analysis sought to evaluate the effects of conjugated linoleic acid (CLA) supplementation on glycemic control, adipokines,... (Meta-Analysis)
Meta-Analysis Review
The effects of conjugated linoleic acid supplementation on glycemic control, adipokines, cytokines, malondialdehyde and liver function enzymes in patients at risk of cardiovascular disease: a GRADE-assessed systematic review and dose-response meta-analysis.
BACKGROUND
The present systematic review and meta-analysis sought to evaluate the effects of conjugated linoleic acid (CLA) supplementation on glycemic control, adipokines, cytokines, malondialdehyde (MDA) and liver function enzymes in patients at risk of cardiovascular disease.
METHODS
Relevant studies were obtained by searching the PubMed, SCOPUS and Web of Science databases (from inception to January 2023). Weighted mean differences (WMD) and 95% confidence intervals (CIs) were pooled using a random-effects model. Heterogeneity, sensitivity analysis, and publication bias were reported using standard methods.
RESULTS
A pooled analysis of 13 randomized controlled trials (RCTs) revealed that CLA supplementation led to a significant increment in fasting blood glucose (FBG) (WMD: 4.49 mg/dL; 95%CI: 2.39 to 6.59; P < 0.001), and aspartate aminotransferase (AST) (WMD: 2.54 IU/L; 95%CI: 0.06 to 5.01; P = 0.044). Moreover, CLA supplementation decreased leptin (WMD: -1.69 ng/ml; 95% CI: -1.80 to -1.58; P < 0.001), and interleukin 6 (IL-6) (WMD: -0.44 pg/ml; 95%CI: -0.86 to -0.02; P = 0.037). However, there was no effect on hemoglobin A1c (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and alanine aminotransferase (ALT) adiponectin compared to the control group.
CONCLUSION
Our findings showed the overall favorable effect of CLA supplementation on the adipokines and cytokines including serum IL-6, and leptin, while increasing FBG and AST. It should be noted that the mentioned metabolic effects of CLA consumption were small and may not reach clinical importance.
PROSPERO REGISTERATION COD
CRD42023426374.
Topics: Humans; Dietary Supplements; Leptin; Cytokines; Linoleic Acids, Conjugated; Interleukin-6; Adipokines; Cardiovascular Diseases; Glycemic Control; Malondialdehyde; Liver; Blood Glucose
PubMed: 37794481
DOI: 10.1186/s12937-023-00876-3 -
JBMR Plus Nov 2023Diabetes poses a significant risk to bone health, with Type 1 diabetes (T1D) having a more detrimental impact than Type 2 diabetes (T2D). The group of hormones known as... (Review)
Review
Diabetes poses a significant risk to bone health, with Type 1 diabetes (T1D) having a more detrimental impact than Type 2 diabetes (T2D). The group of hormones known as incretins, which includes gastric inhibitory peptide (GIP) and glucagon-like peptide 1 (GLP-1), play a role in regulating bowel function and insulin secretion during feeding. GLP-1 receptor agonists (GLP-1 RAs) are emerging as the primary treatment choice in T2D, particularly when atherosclerotic cardiovascular disease is present. Dipeptidyl peptidase 4 inhibitors (DPP-4is), although less potent than GLP-1 RAs, can also be used. Additionally, GLP-1 RAs, either alone or in combination with GIP, may be employed to address overweight and obesity. Since feeding influences bone turnover, a relationship has been established between incretins and bone health. To explore this relationship, we conducted a systematic literature review following the PRISMA guidelines. While some studies on cells and animals have suggested positive effects of incretins on bone cells, turnover, and bone density, human studies have yielded either no or limited and conflicting results regarding their impact on bone mineral density (BMD) and fracture risk. The effect on fracture risk may vary depending on the choice of comparison drug and the duration of follow-up, which was often limited in several studies. Nevertheless, GLP-1 RAs may hold promise for people with T2D who have multiple fracture risk factors and poor metabolic control. Furthermore, a potential new area of interest is the use of GLP-1 RAs in fracture prevention among overweight and obese people. Based on this systematic review, existing evidence remains insufficient to support a positive or a superior effect on bone health to reduce fracture risk in people with T2D. © 2023 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
PubMed: 38025038
DOI: 10.1002/jbm4.10817 -
The British Journal of Nutrition May 2024Vitamin D is a vital indicator of musculoskeletal health, as it plays an important role through the regulation of bone and mineral metabolism. This meta-analysis was... (Meta-Analysis)
Meta-Analysis Review
Vitamin D is a vital indicator of musculoskeletal health, as it plays an important role through the regulation of bone and mineral metabolism. This meta-analysis was performed to investigate the effects of vitamin D supplementation/fortification on bone turnover markers in women. All human randomised clinical trials reported changes in bone resorption markers (serum C-terminal telopeptide of type-I collagen (sCTX) and urinary type I collagen cross-linked N-telopeptide (uNTX)) or bone formation factors (osteocalcin (OC), bone alkaline phosphatase (BALP) and procollagen type-1 intact N-terminal propeptide (P1NP)) following vitamin D administration in women (aged ≥ 18 years) were considered. Mean differences (MD) and their respective 95 % CI were calculated based on fixed or random effects models according to the heterogeneity status. Subgroup analyses, meta-regression models, sensitivity analysis, risk of bias, publication bias and the quality of the included studies were also evaluated. We found that vitamin D supplementation had considerable effect on sCTX (MD: -0·038, 22) and OC (MD: -0·610, 24) with high heterogeneity and uNTX (MD: -8·188, 6) without heterogeneity. Our results showed that age, sample size, dose, duration, baseline vitamin D level, study region and quality of studies might be sources of heterogeneity in this meta-analysis. Subgroup analysis also revealed significant reductions in P1NP level in dose less than 600 μg/d and larger study sample size (>100 participants). Moreover, no significant change was found in BALP level. Vitamin D supplementation/fortification significantly reduced bone resorption markers in women. However, results were inconsistent for bone formation markers.
Topics: Humans; Vitamin D; Female; Dietary Supplements; Biomarkers; Bone Remodeling; Randomized Controlled Trials as Topic; Bone Resorption; Collagen Type I; Bone and Bones; Osteocalcin; Alkaline Phosphatase; Peptides; Food, Fortified
PubMed: 38221822
DOI: 10.1017/S0007114524000060 -
European Journal of Endocrinology Aug 2023Postpartum depression (PPD) has a major impact on maternal and offspring well-being, with multiple possible risk factors: Studies on the association of thyroid... (Meta-Analysis)
Meta-Analysis
Association of gestational thyroid function and thyroid peroxidase antibody positivity with postpartum depression: a prospective cohort study and systematic literature review with meta-analysis.
IMPORTANCE
Postpartum depression (PPD) has a major impact on maternal and offspring well-being, with multiple possible risk factors: Studies on the association of thyroid peroxidase antibody (TPOAb) positivity and thyroid function with PPD provide heterogeneous results.
OBJECTIVE
To study the association of thyroid function and TPOAb positivity with PPD.
DESIGN
We assessed the association of TPOAb and thyroid function with PPD in a population-based prospective cohort study and performed a systematic literature review and meta-analysis.
METHODS
We measured thyroid stimulating hormone (TSH), free thyroxine (FT4), and TPOAb between 9- and 17-week gestation. Postpartum depression was assessed with Edinburgh Postpartum Depression Scale at 2-month postpartum and Brief Symptom Inventory at 2-, 6-, and 36-month postpartum. Additionally, we performed a systematic literature review and meta-analysis assessing this association.
RESULTS
In the present study, there was no association of thyroid function with PPD (TSH: odds ratio [OR] 0.83, 95% CI 0.58-1.19, P = .32; FT4: OR 0.99, 95% CI 0.95-1.05, P = .86) or TPOAb positivity with PPD (OR 0.79, 95% CI 0.47-1.33, P = .37). An impaired thyroidal response to human chorionic gonadotropin (hCG), a surrogate marker for TPOAb positivity, was associated with a lower risk of PPD (P for interaction TSH = 0.04; FT4 = 0.06). Our systematic review and meta-analysis included 3 articles that were combined with the present study. There was no statistically significant association of TPOAb positivity with PPD (OR 1.93, 95% CI 0.91-4.10, P = .08), but the results were heterogeneous (I2 = 79%).
CONCLUSIONS AND RELEVANCE
There was no significant association of TPOAb positivity, TSH, or FT4 with PPD. Our systematic review and meta-analysis revealed high heterogeneity of the current literature. Although TPOAb-positive women should be monitored for postpartum thyroiditis, our findings do not support routinely screening for PPD.
Topics: Female; Humans; Thyroid Gland; Iodide Peroxidase; Prospective Studies; Depression, Postpartum; Autoantibodies; Thyrotropin; Thyroxine
PubMed: 37486224
DOI: 10.1093/ejendo/lvad092 -
Gynecological Endocrinology : the... Dec 2023This systematic review and meta-analysis aimed at summarizing the evidence concerning circulating asprosin, and related endocrine and metabolites in women with and... (Meta-Analysis)
Meta-Analysis
This systematic review and meta-analysis aimed at summarizing the evidence concerning circulating asprosin, and related endocrine and metabolites in women with and without the polycystic ovary syndrome (PCOS). We performed a comprehensive literature search in Pubmed, Web of Science, Scielo, and Chinese National Knowledge Infrastructure for studies published until May 20, 2022, that evaluated circulating asprosin levels in women with and without PCOS, regardless of language. The quality of studies was assessed with the Newcastle-Ottawa Scale. Random-effects models were used to estimate mean differences (MD) or standardized MD (SMD) and their 95% confidence interval (CI). We evaluated eight studies reporting 1,050 PCOS cases and 796 controls of reproductive age. Participants with PCOS were younger (MD = -2.40 years, 95% CI -2.46 to -2.33), with higher values of asprosin (SMD = 2.57, 95% CI 1.64-3.50), insulin (SMD = 2.73, 95% CI 1.18-4.28), homeostatic model assessment of insulin resistance (SMD = 2.70, 95% CI 0.85-4.55), luteinizing hormone (SMD = 2.33, 95% CI 0.60-4.06), total testosterone (SMD = 4.06, 95% CI 1.89-6.22), dehydroepiandrosterone sulfate (SMD = 2.38, 95% CI 0.37-4.40), and triglycerides (SMD = 1.20, 95% CI 0.13 to 2.27). Moreover, PCOS women had lower circulating levels of sex hormone-binding globulin (SMD = -3.36, 95% CI -4.92 to -1.80), and high-density lipoprotein-cholesterol (SMD = -0.85, 95% CI -1.69 to -0.01); with no significant differences observed for glucose, total cholesterol, and low-density lipoprotein-cholesterol levels. Circulating asprosin levels were significantly higher in women with PCOS as compared to those without the syndrome.
Topics: Female; Humans; Cholesterol, HDL; Insulin; Insulin Resistance; Luteinizing Hormone; Polycystic Ovary Syndrome
PubMed: 36480935
DOI: 10.1080/09513590.2022.2152790 -
Clinical Medicine & Research Dec 2023Lichen planus (LP) is a chronic autoimmune disease of skin and mucous membranes. World Health Organization has announced oral lichen planus (OLP) as a premalignant... (Review)
Review
Lichen planus (LP) is a chronic autoimmune disease of skin and mucous membranes. World Health Organization has announced oral lichen planus (OLP) as a premalignant lesion. The exact etiology of OLP remains unknown; however, different mechanisms may be involved in its immunopathogenesis. The upregulation of cytokines, chemokines, and adhesion molecules is consistent with a persistent and erratic immunological response to OLP-mediated antigens generated by oral keratinocytes and innate immune cells. These molecules attract T cells, and mast cells to the disease site and regulate complex interactions among cells that lead to death of keratinocytes, degradation of basement membrane, and chronicity of the disease. It is believed that CD8+ and CD4+ T helper 1 (Th1) cells are the main lymphocytes involved in this process, although recent evidence suggests implication of other T helper subgroups, such as Th23, Th17, and regulatory T cells (Tregs), proposing a more complex cellular immunity process to be involved in its pathogenesis. The emphasis of this research review is on the function of IL-17 in the pathophysiology of OLP and how current discoveries may point to future treatment strategies. This research protocol will follow Preferred Reporting Items for Systematic Reviews (PRISMA 2020) checklist. An electronic search was conducted in PubMed, Scopus, Google Scholar, Embase, and Cochrane databases for articles published from 1960 to June 2022. Based on the eligibility criteria, 21 articles were enrolled. In comparison to healthy controls, the findings of this review demonstrated greater expression of IL-17 and Th-17 in the blood, saliva, and tissues of OLP and LP patients. Additionally, there was a strong link between the relative levels of IL-17 and IL-23 expression. Treatment with monoclonal antibodies against Th-17/Tc-17, IL-12/IL-23, and IL-23 would result in significant long-term improvement of LP symptoms.
Topics: Humans; Lichen Planus, Oral; Interleukin-17; Cytokines; Lichen Planus; Interleukin-23
PubMed: 38296640
DOI: 10.3121/cmr.2023.1822