2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T790,Postoperative complications such as dry eye, ocular surface pain, and abnormal wound healing responses, including fibrosis or ectasia, remain a significant concern in corneal, refractive, and cataract surgeries as they occur even in those patients without the classical clinical risk factors. Persistent low-grade or subclinical ocular surface inflammation in these patients may have contributed to these suboptimal outcomes. Inflammatory factors such as IL-1β, IL-6, IL-17A, TNFα, IFNγ, and/or MMP-9 are reported to be higher on the ocular surface of patients with either overt or subclinical inflammation. These inflammatory factors disrupt tissue homeostasis and wound healing response as they (i) sensitize nociceptive (pain) pathways, (ii) destabilize cell-cell adhesion, (iii) increase TGFβ-dependent or independent extracellular matrix (ECM) deposition leading to scarring, and/or (iv) cause ectasia by decreasing ECM deposition and natural collagen cross-linking. These effects of molecular risk factors can be mitigated by preoperative BIOLOGICAL CLEANSING strategies designed to reduce the load of these inflammatory factors on the ocular surface. Depending on the clinical presentation and inflammatory load status, biological cleansing using (i) lubricants; (ii) eyelid hygiene; (iii) ocular surface washes; (iv) topical or oral nutraceuticals; (v) nonpharmacological treatments, such as thermal pulsation therapy and intense light therapy; (vi) topical immunomodulators, such as cyclosporine, tacrolimus, steroids, and Lifitegrast; and (vii) lifestyle modifications, such as diet and probiotics, can be followed. We and others have shown a reduction in these inflammatory factors on the ocular surface using one or more of these strategies. Incorporating biological cleansing protocols into presurgical preparation is a vital step toward modulating ocular surface biology to improve postoperative outcomes for patients.31:T7a3,Postoperative complications such as dry eye, ocular surface pain, and abnormal wound healing responses, including fibrosis or ectasia, remain a significant concern in corneal, refractive, and cataract surgeries as they occur even in those patients without the classical clinical risk factors. Persistent low-grade or subclinical ocular surface inflammation in these patients may have contributed to these suboptimal outcomes. Inflammatory factors such as IL-1β, IL-6, IL-17A, TNFα, IFNγ, and/or MMP-9 are reported to be higher on the ocular surface of patients with either overt or subclinical inflammation. These inflammatory factors disrupt tissue homeostasis and wound healing response as they (i) sensitize nociceptive (pain) pathways, (ii) destabilize cell–cell adhesion, (iii) increase TGFβ-dependent or independent extracellular matrix (ECM) deposition leading to scarring, and/or (iv) cause ectasia by decreasing ECM deposition and natural collagen cross-linking. These effects of molecular risk factors can be mitigated by preoperative BIOLOGICAL CLEANSING strategies designed to reduce the load of these inflammatory factors on the ocular surface. Depending on the clinical presentation and inflammatory load status, biological cleansing using (i) lubricants; (ii) eyelid hygiene; (iii) ocular surface washes; (iv) topical or oral nutraceuticals; (v) nonpharmacological treatments, such as thermal pulsation therapy and intense light therapy; (vi) topical immunomodulators, such as cyclosporine, tacrolimus, steroids, and Lifitegrast; and (vii) lifestyle modifications, such as diet and probiotics, can be followed. We and others have shown a reduction in these inflammatory factors on the ocular surface using one or more of these strategies. Incorporating biological cleansing protocols into presurgical preparation is a vital step toward modulating ocular surface biology to improve postoperative outcomes for patients.32:T6db,Obesity is an already identified risk factor for various noncommunicable diseases. Berberine is an alkaloid that has manifested a significant effect in the treatment of obesity and its complications. The aim of this systematic review and meta analysis is to evaluate the effect of berberine on obesity indices. We conducted a comprehensive search of Scopus, PubMed, Web of Science, and Google Scholar for randomized controlled trials (RCTs) investigating berberine's impact on obesity indices in adults. Eligible studies included human trials with quantitative outcomes for weight, BMI, WC, or WHR. Animal studies, reviews, and non-RCTs were excluded. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane RoB 2 tool. A random-effects meta-analysis was performed to calculate mean differences (MDs) and 95% confidence intervals (CIs). Heterogeneity was evaluated using I² statistics. A total of 23 articles were included. Berberine significantly reduced body weight (MD of -0.88 kg, 95% CI: -1.36 to -0.39, p = 0.0003), BMI (MD of -0.48 kg/m², 95% CI: -0.89 to -0.07, p < 0.0216), and WC (MD of -1.32 kg/m², 95% CI: -2.24 to -0.41, p < 0.0046). However, berberine did not significantly reduce WHR compared to control groups (MD of -0.01, 95% CI: -0.03 to 0.01). Meta-regression revealed no association between berberine use and age. Berberine use significantly reduces body weight, BMI, and WC but does not significantly reduce WHR. Future trials should focus on improving reporting standards for biochemical characterization (such as purity, potency and gram amounts) and address common biases such as lack of blinding and randomization to enhance the reliability of the evidence.33:T6ed,Society values a full head of hair. Therefore, androgenetic hair loss (AGA), though medically benign, can cause significant emotional distress. There is strong demand for alternative (nonconventional, over-the-counter) AGA treatments. It is important to have evidence on the efficacy of these treatments for AGA-especially in comparison with treatments that are approved by the United States Food and Drug Administration (FDA), such as oral finasteride and topical minoxidil. Following a systematic review, we conducted a network meta-analysis (NMA) to determine the relative efficacy of conventional monotherapies and selected alternative (nonconventional, over-the-counter) products for male AGA. We conducted a Bayesian NMA under a fixed effect model with uniform priors; the NMA estimated relative effects-as per mean difference (MD), along with the 95% credible interval (CI)-and surface under the cumulative ranking curve (SUCRA) values. We also assessed study-level evidence quality. Eligible studies were identified through systematic searches (without date restrictions) in PubMed and Scopus on April 30, 2025. The main outcome measure was change in total hair density at 24 weeks from baseline (in hairs/cm We found 24 eligible trials-where the relative efficacy of eight conventional monotherapies and seven alternative (nonconventional, over-the-counter) products was determined. The current NMA study confirms the efficacy of conventional monotherapies such as oral dutasteride, topical/oral minoxidil, and oral/topical finasteride for male AGA. We have provided guidance regarding the relative efficacy of some alternative (nonconventional, over-the-counter) agents (e.g., melatonin (topical) and rosemary oil (topical)) compared to conventional treatments.34:T866,ABSTRACTBackgroundSociety values a full head of hair. Therefore, androgenetic hair loss (AGA), though medically benign, can cause significant emotional distress. There is strong demand for alternative (nonconventional, over‐the‐counter) AGA treatments. It is important to have evidence on the efficacy of these treatments for AGA—especially in comparison with treatments that are approved by the United States Food and Drug Administration (FDA), such as oral finasteride and topical minoxidil.AimsFollowing a systematic review, we conducted a network meta‐analysis (NMA) to determine the relative efficacy of conventional monotherapies and selected alternative (nonconventional, over‐the‐counter) products for male AGA.MethodsWe conducted a Bayesian NMA under a fixed effect model with uniform priors; the NMA estimated relative effects—as per mean difference (MD), along with the 95% credible interval (CI)—and surface under the cumulative ranking curve (SUCRA) values. We also assessed study‐level evidence quality. Eligible studies were identified through systematic searches (without date restrictions) in PubMed and Scopus on April 30, 2025. The main outcome measure was change in total hair density at 24 weeks from baseline (in hairs/cm2).Results and ConclusionWe found 24 eligible trials—where the relative efficacy of eight conventional monotherapies and seven alternative (nonconventional, over‐the‐counter) products was determined. The current NMA study confirms the efficacy of conventional monotherapies such as oral dutasteride, topical/oral minoxidil, and oral/topical finasteride for male AGA. We have provided guidance regarding the relative efficacy of some alternative (nonconventional, over‐the‐counter) agents (e.g., melatonin (topical) and rosemary oil (topical)) compared to conventional treatments.25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Nutraceutical: modality Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Nutraceutical (modality). 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pooling across brands was not performed but both appear in the analysis.","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03759-1","tag_type":"warning","value":"The network includes 137 distinct compound combinations across 163 trials, making many node comparisons sparse and indirect; transitivity assumptions may not fully hold.","value_numeric":null}],"summaries":{"what_studied":"A systematic review and network meta-analysis of 163 RCTs (n = 15,757) evaluated nutraceuticals and phytoceuticals vs. placebo or antidepressants (TAU) for major depressive disorder (MDD), examining depressive symptoms, treatment response, remission, anxiety, tolerability, and acceptability.","key_result":"After restricting to high-quality evidence (≥2 RCTs, low risk of bias, non-sponsored, non-outlier), EPA (SMD = −1.67), vitamin D3 (SMD = −1.59), and St. John's wort extract ZE117 (SMD = −1.02) showed the largest effect sizes vs. placebo for depressive symptoms — but these effect sizes were deemed higher-than-expected or unrealistic. Curcumin showed a moderate benefit for anxiety (SMD = −0.58). Citicoline was linked to significantly more dropouts. Overall confidence in evidence was **low to very low**, and larger effect sizes correlated with lower study quality (meta-regression).","limitations":"- Substantial heterogeneity (I² = 85.3%) and significant global inconsistency limit pooled estimates.\n- Confidence in all evidence rated low to very low (CINeMA/AMSTAR-Plus).\n- Even filtered analyses produced effect sizes judged unrealistically large, suggesting residual bias.","practice_takeaway":"Clinicians should be cautious about recommending nutraceuticals or phytoceuticals for MDD — current evidence is low quality, and apparent large benefits (especially for EPA, vitamin D3, and St. John's wort) are likely inflated by poor study design. Rigorous, well-powered RCTs are needed before routine use can be supported."}},{"doi":"10.1136/bmj-2026-100216","pmid":"42580772","title":"Evidence based interventions for bipolar disorder across phases and age groups: living umbrella review, evaluation, analysis, and communication hub (U-REACH) project","journal_title":"BMJ","journal_issn":"1756-1833","published_at":"2026-08-11T00:00:00.000Z","url":"https://doi.org/10.1136/bmj-2026-100216","source_score":89,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-17T13:33:30.432Z","updated_at":"2026-08-17T13:33:30.432Z","tags":[{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"brand","value":"Caplyta","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"brand","value":"Latuda","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"brand","value":"Vraylar","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"category","value":"Medicine, General & Internal","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"condition","value":"Bipolar Disorder","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"aripiprazole","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"asenapine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"carbamazepine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"cariprazine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"divalproex","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"fluoxetine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"haloperidol","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"ketamine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"lamotrigine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"lithium","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"lumateperone","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"lurasidone","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"olanzapine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"paliperidone","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"quetiapine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"risperidone","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"tamoxifen","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"valproate","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"ziprasidone","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"modality","value":"Atypical Antipsychotic","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"modality","value":"Brain Stimulation","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"modality","value":"Mood Stabilizer","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"modality","value":"NMDA Receptor Antagonist","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"modality","value":"Nutraceutical","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"modality","value":"Psychosocial Intervention","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"sample_size","value":"n=77","value_numeric":77},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"study_design","value":"Umbrella Review (Living Systematic Review with Meta-Analyses)","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"warning","value":"Study design label 'Umbrella Review' is a non-standard design category; it is a higher-order synthesis above standard systematic reviews and meta-analyses.","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"warning","value":"Tamoxifen is listed as effective for adult mania — this is an uncommon clinical use (PKC inhibition mechanism) and may surprise readers unfamiliar with this evidence base.","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"warning","value":"The 'practice_changing' impact flag is applied because this is a comprehensive living umbrella review with an open-access clinical decision tool, though individual treatment effect sizes are not extractable from the abstract alone.","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"warning","value":"The sample_size tag reflects the number of included systematic reviews (n=77), not individual patient-level N, which is not reported as a single aggregate in the abstract.","value_numeric":null}],"summaries":{"what_studied":"A living umbrella review (U-REACH) evaluated the certainty of evidence for pharmacological, nutraceutical, psychosocial, brain stimulation, and circadian rhythm-based treatments across all bipolar disorder phases (depression, mania/mixed, maintenance) and age groups (adults; children/adolescents), using 77 systematic reviews (21 network meta-analyses, 56 pairwise meta-analyses) published up to November 2024.","key_result":"Across 2,510 meta-analyses covering 133 outcomes and 116 unique treatments, GRADE ratings were high (n=236), moderate (n=827), low (n=986), and very low (n=461). Agents effective across multiple phases in adults included aripiprazole, asenapine, cariprazine, divalproex/valproate, lamotrigine, lithium, olanzapine, paliperidone, quetiapine, and risperidone; in youth, lurasidone and olanzapine-fluoxetine were supported for bipolar depression, and aripiprazole, asenapine, olanzapine, quetiapine, and risperidone for mania.","limitations":"Most evidence is rated low or very low certainty (1,447 of 2,510 meta-analyses), limiting confidence in many treatment estimates; the umbrella review design inherits limitations of the included meta-analyses (e.g., heterogeneity, publication bias); pediatric data are sparse compared with adult data.","practice_takeaway":"Use the freely available EBI-BD platform (ebibd-database.org) to identify phase- and age-specific evidence-based options and discuss patient-preferred safety profiles using its 12-intervention, 17-outcome preference tool. For cross-phase adult coverage, lithium, quetiapine, olanzapine, aripiprazole, and divalproex/valproate have the broadest support; for youth, lurasidone (bipolar depression) and aripiprazole (mania) have the strongest pediatric evidence."}},{"doi":"10.1016/j.jad.2026.122277","pmid":"42462928","title":"A randomized trial of omega-3 fatty acids plus inositol versus N-acetylcysteine for the treatment of depression and mania in emotionally dysregulated youth age 5–17 with and without autism traits","journal_title":"Journal of Affective Disorders","journal_issn":"0165-0327","published_at":"2026-07-16T00:00:00.000Z","url":"https://doi.org/10.1016/j.jad.2026.122277","source_score":12,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-26T13:44:38.609Z","updated_at":"2026-07-26T13:44:38.609Z","tags":[{"paper_doi":"10.1016/j.jad.2026.122277","tag_type":"age_group","value":"adolescent","value_numeric":null},{"paper_doi":"10.1016/j.jad.2026.122277","tag_type":"age_group","value":"child","value_numeric":null},{"paper_doi":"10.1016/j.jad.2026.122277","tag_type":"age_group","value":"pediatric","value_numeric":null},{"paper_doi":"10.1016/j.jad.2026.122277","tag_type":"category","value":"Psychiatry","value_numeric":null},{"paper_doi":"10.1016/j.jad.2026.122277","tag_type":"condition","value":"Autism Spectrum Disorder","value_numeric":null},{"paper_doi":"10.1016/j.jad.2026.122277","tag_type":"condition","value":"Depression","value_numeric":null},{"paper_doi":"10.1016/j.jad.2026.122277","tag_type":"condition","value":"Emotional Dysregulation","value_numeric":null},{"paper_doi":"10.1016/j.jad.2026.122277","tag_type":"condition","value":"Mania","value_numeric":null},{"paper_doi":"10.1016/j.jad.2026.122277","tag_type":"generic","value":"inositol","value_numeric":null},{"paper_doi":"10.1016/j.jad.2026.122277","tag_type":"generic","value":"N-acetylcysteine","value_numeric":null},{"paper_doi":"10.1016/j.jad.2026.122277","tag_type":"generic","value":"omega-3 fatty acids","value_numeric":null},{"paper_doi":"10.1016/j.jad.2026.122277","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1016/j.jad.2026.122277","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1016/j.jad.2026.122277","tag_type":"modality","value":"Nutraceutical","value_numeric":null},{"paper_doi":"10.1016/j.jad.2026.122277","tag_type":"modality","value":"Omega-3 Fatty Acid","value_numeric":null},{"paper_doi":"10.1016/j.jad.2026.122277","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.jad.2026.122277","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1016/j.jad.2026.122277","tag_type":"warning","value":"The trial was open-label, not double-blind, which substantially increases risk of bias in outcome assessment. Between-group comparisons were non-significant, and the abstract does not report the total sample size (N), limiting confidence in effect size estimates. The level of evidence is provisionally set to 2 given the RCT design, but the open-label methodology may warrant downgrading. 'Autism traits' were defined dimensionally by CBCL score rather than formal DSM diagnosis, so findings may not generalize to clinically diagnosed ASD populations.","value_numeric":null}],"summaries":{"what_studied":"This RCT compared omega-3 fatty acids plus inositol (O3I: 1020 mg EPA + 1000–2000 mg inositol) versus N-acetylcysteine (NAC: 1800–2700 mg/day) as open-label treatments over 6 weeks in children and adolescents aged 5–17 with emotional dysregulation, with or without autism traits (AT) defined by CBCL scores.","key_result":"Both O3I and NAC produced modest improvements in depression and mania with no significant between-group difference overall. O3I showed statistically significant within-group improvement in depression (CDI); NAC showed a greater (but non-significant) decrease in mania (P-YMRS). In youth with AT, NAC outperformed O3I for mania and produced significant within-group improvements on SRS and BRIEF scores.","limitations":"Open-label design introduces performance and detection bias. The 6-week duration is short for assessing sustained benefit. Sample size and power are not reported in the abstract, limiting interpretation of non-significant between-group comparisons.","practice_takeaway":"For emotionally dysregulated youth aged 5–17, both O3I and NAC appear modestly beneficial; clinicians may favor NAC when autism traits and mania are prominent. Neither treatment showed a clear superiority overall, so either may be a reasonable first-line nutraceutical option pending larger blinded trials."}},{"doi":"10.3389/fneur.2026.1853951","pmid":null,"title":"Pathogen effects on the brain: the case of SARS-CoV-2 spike protein and neuro COVID","journal_title":"Frontiers in Neurology","journal_issn":"1664-2295","published_at":"2026-07-13T00:00:00.000Z","url":"https://doi.org/10.3389/fneur.2026.1853951","source_score":45,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":false,"crossref":true,"unpaywall":true},"created_at":"2026-07-18T13:39:59.192Z","updated_at":"2026-07-18T13:39:59.192Z","tags":[{"paper_doi":"10.3389/fneur.2026.1853951","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.3389/fneur.2026.1853951","tag_type":"category","value":"Neurosciences","value_numeric":null},{"paper_doi":"10.3389/fneur.2026.1853951","tag_type":"condition","value":"COVID-19","value_numeric":null},{"paper_doi":"10.3389/fneur.2026.1853951","tag_type":"condition","value":"Long-COVID","value_numeric":null},{"paper_doi":"10.3389/fneur.2026.1853951","tag_type":"condition","value":"Neuroinflammation","value_numeric":null},{"paper_doi":"10.3389/fneur.2026.1853951","tag_type":"generic","value":"eriodictyol","value_numeric":null},{"paper_doi":"10.3389/fneur.2026.1853951","tag_type":"generic","value":"hydroxytyrosol","value_numeric":null},{"paper_doi":"10.3389/fneur.2026.1853951","tag_type":"generic","value":"luteolin","value_numeric":null},{"paper_doi":"10.3389/fneur.2026.1853951","tag_type":"generic","value":"oleuropein","value_numeric":null},{"paper_doi":"10.3389/fneur.2026.1853951","tag_type":"generic","value":"sulforaphane","value_numeric":null},{"paper_doi":"10.3389/fneur.2026.1853951","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.3389/fneur.2026.1853951","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.3389/fneur.2026.1853951","tag_type":"modality","value":"Flavonoid","value_numeric":null},{"paper_doi":"10.3389/fneur.2026.1853951","tag_type":"modality","value":"Nutraceutical","value_numeric":null},{"paper_doi":"10.3389/fneur.2026.1853951","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.3389/fneur.2026.1853951","tag_type":"warning","value":"No primary data or patient cohort; all mechanistic conclusions are based on synthesized prior literature, not new experimental findings.","value_numeric":null},{"paper_doi":"10.3389/fneur.2026.1853951","tag_type":"warning","value":"Study design is ambiguous between a narrative review and a perspective/opinion piece; tagged as Narrative Review based on content, but no formal systematic methodology is described.","value_numeric":null},{"paper_doi":"10.3389/fneur.2026.1853951","tag_type":"warning","value":"The claim that Long-COVID affects 'up to 50%' of SARS-CoV-2 patients is stated without a cited source in the abstract — clinicians should verify this estimate against current epidemiological literature.","value_numeric":null}],"summaries":{"what_studied":"This narrative review examines how the SARS-CoV-2 Spike protein persists in tissue reservoirs (especially the meninges) and drives neuroinflammation via mast cell and microglial activation, contributing to Long-COVID cognitive and neuropsychiatric symptoms.","key_result":"Spike protein is proposed to stimulate meningeal mast cells and microglia to release pro-inflammatory, neurotoxic, and vasoactive mediators (including histamine, IL-6, TNF, and tryptase), leading to blood-brain barrier disruption and maladaptive synaptic pruning; flavonoids such as luteolin and eriodictyol, along with oleuropein, sulforaphane, and hydroxytyrosol, are identified as potential inhibitors of these pathways.","limitations":"- Narrative review with no primary clinical data or patient cohort; mechanistic claims are largely inferential.\n- Prevalence figure of Long-COVID affecting \"up to 50%\" of patients is cited without a specific referenced study in the abstract.\n- No clinical trial evidence is presented for the proposed flavonoid or nutraceutical interventions.","practice_takeaway":"Clinicians should be aware that persistent Spike protein in the meninges may sustain neuroinflammation in Long-COVID patients presenting with brain fog or neuropsychiatric symptoms. Anti-inflammatory strategies targeting mast cell and microglial activation are under investigation, but no intervention reviewed here has established clinical trial support yet."}},{"doi":"10.1016/j.cmet.2026.04.006","pmid":"42102814","title":"Garlic-derived metabolite activates LKB1, promotes adipose eNAMPT secretion, and improves age-related muscle function via hypothalamic signaling","journal_title":"Cell Metabolism","journal_issn":"1550-4131","published_at":"2026-05-09T00:00:00.000Z","url":"https://doi.org/10.1016/j.cmet.2026.04.006","source_score":347,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-05-10","doi":"10.1016/j.cmet.2026.04.006","days":"7","issn":"1550-4131","rank":"1","field":"Clinical Medicine","score":"347","category":"Endocrinology & Metabolism","categories":["Endocrinology & Metabolism"],"_categories":["Endocrinology & Metabolism"]},"pubmed":{"doi":"10.1016/j.cmet.2026.04.006","title":"Garlic-derived metabolite activates LKB1, promotes adipose eNAMPT secretion, and improves age-related muscle function via hypothalamic signaling.","journal":"Cell metabolism","methods":"","results":"","abstract":"Garlic (Allium sativum L.) and its aged extract contain many bioactive compounds that can bring health benefits to humans. Among them, S-1-propenyl-L-cysteine (S1PC) has recently drawn significant attention in the field of nutriceutical research. However, the mechanism of its molecular action has remained poorly understood. Here, we show that S1PC significantly activates liver kinase B1 (LKB1) through enhancing its tertiary complex formation with STRAD and MO25, leading to stimulating the phosphorylation of a mammalian NAD","keywords":["LKB1","S-1-propenyl-L-cysteine","SIRT1","aging","garlic","hypothalamus","liver kinase B1","phosphorylation","skeletal muscle","white adipose tissue"],"pubmed_id":"42102814","conclusions":"","publication_date":"2026-05-09T00:00:00"},"crossref":{"DOI":"10.1016/j.cmet.2026.04.006","URL":"https://doi.org/10.1016/j.cmet.2026.04.006","ISSN":["1550-4131"],"link":[{"URL":"https://api.elsevier.com/content/article/PII:S1550413126001440?httpAccept=text/xml","content-type":"text/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https://api.elsevier.com/content/article/PII:S1550413126001440?httpAccept=text/plain","content-type":"text/plain","content-version":"vor","intended-application":"text-mining"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Garlic-derived metabolite activates LKB1, promotes adipose eNAMPT secretion, and improves age-related muscle function via hypothalamic signaling"],"author":[{"given":"Jun-ichiro","family":"Suzuki","sequence":"first","affiliation":[]},{"given":"Kiyoshi","family":"Yoshioka","sequence":"additional","affiliation":[]},{"given":"Masahiro","family":"Kurita","sequence":"additional","affiliation":[]},{"given":"Takumi","family":"Sugimoto","sequence":"additional","affiliation":[]},{"given":"Takahiro","family":"Eguchi","sequence":"additional","affiliation":[]},{"given":"Naoki","family":"Ito","sequence":"additional","affiliation":[]},{"given":"Aoi","family":"Kodama","sequence":"additional","affiliation":[]},{"given":"Yasutomi","family":"Kamei","sequence":"additional","affiliation":[]},{"given":"Masahiro","family":"Ohtani","sequence":"additional","affiliation":[]},{"given":"Toshiaki","family":"Matsutomo","sequence":"additional","affiliation":[]},{"given":"Shin-ichiro","family":"Imai","sequence":"additional","affiliation":[]}],"issued":{"date-parts":[[2026,5]]},"member":"78","prefix":"10.1016","source":"Crossref","volume":null,"created":{"date-time":"2026-05-07T14:58:05Z","timestamp":1778165885000,"date-parts":[[2026,5,7]]},"indexed":{"date-time":"2026-05-07T15:16:42Z","timestamp":1778167002138,"date-parts":[[2026,5,7]]},"license":[{"URL":"https://www.elsevier.com/tdm/userlicense/1.0/","start":{"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000,"date-parts":[[2026,5,1]]},"delay-in-days":0,"content-version":"tdm"},{"URL":"https://www.elsevier.com/legal/tdmrep-license","start":{"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000,"date-parts":[[2026,5,1]]},"delay-in-days":0,"content-version":"tdm"},{"URL":"http://creativecommons.org/licenses/by/4.0/","start":{"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000,"date-parts":[[2026,4,9]]},"delay-in-days":0,"content-version":"vor"}],"subject":[],"abstract":null,"language":"en","relation":{},"resource":{"primary":{"URL":"https://linkinghub.elsevier.com/retrieve/pii/S1550413126001440"}},"subtitle":[],"assertion":[{"name":"publisher","label":"This article is maintained by","value":"Elsevier"},{"name":"articletitle","label":"Article Title","value":"Garlic-derived metabolite activates LKB1, promotes adipose eNAMPT secretion, and improves age-related muscle function via hypothalamic signaling"},{"name":"journaltitle","label":"Journal Title","value":"Cell Metabolism"},{"name":"articlelink","label":"CrossRef DOI link to publisher maintained version","value":"https://doi.org/10.1016/j.cmet.2026.04.006"},{"name":"content_type","label":"Content Type","value":"article"},{"name":"copyright","label":"Copyright","value":"© 2026 The Author(s). Published by Elsevier Inc."}],"deposited":{"date-time":"2026-05-07T14:58:10Z","timestamp":1778165890000,"date-parts":[[2026,5,7]]},"issn-type":[{"type":"print","value":"1550-4131"}],"published":{"date-parts":[[2026,5]]},"publisher":"Elsevier BV","reference":[{"DOI":"10.1016/j.cmet.2023.12.007","key":"10.1016/j.cmet.2026.04.006_bib1","year":"2024","issue":null,"author":"Guarente","volume":"36","first-page":"354","unstructured":null,"article-title":"Human trials exploring anti-aging medicines","journal-title":"Cell Metab.","doi-asserted-by":"crossref"},{"DOI":"10.1038/s41591-022-01923-y","key":"10.1016/j.cmet.2026.04.006_bib2","year":"2022","issue":null,"author":"Chaib","volume":"28","first-page":"1556","unstructured":null,"article-title":"Cellular senescence and senolytics: the path to the clinic","journal-title":"Nat. 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Berberine significantly reduced body weight (MD of -0.88 kg, 95% CI: -1.36 to -0.39, p = 0.0003), BMI (MD of -0.48 kg/m², 95% CI: -0.89 to -0.07, p < 0.0216), and WC (MD of -1.32 kg/m², 95% CI: -2.24 to -0.41, p < 0.0046). However, berberine did not significantly reduce WHR compared to control groups (MD of -0.01, 95% CI: -0.03 to 0.01). Meta-regression revealed no association between berberine use and age.","abstract":"$32","keywords":[],"pubmed_id":"41310257","conclusions":"Berberine use significantly reduces body weight, BMI, and WC but does not significantly reduce WHR. 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Versus control, network estimates showed mean hair density gains at 24 weeks for minoxidil 5% topical: +20.0 hairs/cm² (95% CrI 3.7 to 41.0), dutasteride 0.5 mg oral: +19.0 (9.5 to 28.0), finasteride 0.25% topical: +15.0 (0.85 to 30.0), and finasteride 1 mg oral: +12.0 (4.20 to 19.0); OTC agents ranked mid to low (e.g., rosemary topical SUCRA 53.6%; melatonin topical 55.4%; saw palmetto topical 14.1%).","limitations":"Efficacy was assessed only at 24 weeks; baseline disease duration was not accounted for. Many alternative‑agent trials enrolled relatively small numbers, and several studies showed risk‑of‑bias concerns. Network geometry limited some node‑splitting inconsistency assessments.","practice_takeaway":"At 6 months, dutasteride 0.5 mg daily ranks highest for increasing hair density, with finasteride (oral/topical) and topical minoxidil also outperforming control by clinically meaningful margins. OTC options like topical rosemary and melatonin show modest relative efficacy, while saw palmetto ranks low—use these data to set expectations when discussing nonprescription alternatives."}}],"initialOffset":8,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"modality","value":"Nutraceutical"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Modalities","href":"/hub/tag/modality"},{"name":"Nutraceutical"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"modality","hub_tag_value":"Nutraceutical"}}}]]

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