Exploratory study of sublimed sulfur, in cognitively normal subjects and in Alzheimer’s dementia (AD) subjects: implications for Sulfur targeting Hydrogen sulfide (H2S)/Homocysteine (Hcy) and beta-galactosidase (GALAC)/Autophagy Signaling in AD
Bibliographic record
Abstract
Introduction: There is mounting evidence to suggest that hyper-homocysteinemia (eHct) correlates with cognitive decline severity and cortical atrophy in AD.Hydrogen Sulfide (H 2 S) exerts neuroprotection through regulating Homocysteine (eHcy) signaling.Elemental sulfur can mediate H 2 S neuroprotection through the trans-sulfuration pathway and correct the the dysregulation of H 2 S /Hct signaling in AD.Sublimed Sulfur, formulated as SULMEDOL and approved for the treatment of lactose intolerance, activates gut beta-galactosidase (GALAC).We repurpose Sulmedol from lactose intolerance to likely CNS effect, since gut GALAC cross-talks with senescence-related GALAC expression in the brain.In view of the known regulatory function of GALAC in CNS endosomal-lysosomal autophagy system , we propose that SULMEDOL may rescue aberrant autophagy in AD. Methods:We hypothesize that sublimed Sulfur (SS), via targeting H2S/Hcy and GALAC, may be efficacious in AD.In study I, we examined the 30-day treatment effects of SS at daily dosage of 200 mg to be administered at in altering the plasma Hcy levels in a small cohort of cognitive normal subjects.We stratified the cohort of cognitively normal control subjects to be administered SS into three groups with pre-determined range of basal fHCy levels as follows: Group 1 (n=16): range of fHcy 10.0-22.1 µmol/L; Group 2(n=15) fHcy range:7.1-9.9 µmol/L;Group 3 (n=15); range of fHcy 2.3-7.0 µmol/L .Primary outcome was defined as change in Hcy from baseline to 24-hr and 30-day post-treatment period.In study II, we evaluated the safety and tolerability of SS in two AD patients were treated with 200 mg for 3 months, with Clinical Global Impression-Global Improvement (CGI -I) scale as the primary outcome measure. Results:In Study I, Group I subjects, fHcy decreased significantly by 36.1%, 24 hours after treatment and by 29.3%, 30 days later.In Group 2 fHcy did not change significantly.Group 3 exhibited paradoxical non-significant increase in fHcy, without change in erythrocyte folic acid, serum lipids and vitamin B12.SS was well tolerated in all patients.In Study II, clinical vignette analysis of two AD patients revealed that 3-month SS treatment ameliorated cluster of AD symptoms: nocturnal wandering, paranoid delusions, disorientation and confusion.CGI-I scale score was "very much improved".No serious adverse events were reported.Conclusions: SS in dual targeting H2S-homocysteine inflammation signaling and GALAC autophagy pathway related to AD, holds promise in therapeutic development of AD.Our findings warrant controlled trial of SS in AD.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".