Unaffiliated Researcher

independent researcher

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Internship @ MVOL – TMU : From October 3rd to December 31st              

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Link to: Cross-disciplinary recent studies implicating D-xylose in disease severity and immune modulation

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 Summary of a very long discussion with AIs…about the statement: “HS promotes viral infection.”  —>  
Does HS promote viral infections?
                     

Link: https://unaffiliated-researchers.com/wp-content/uploads/2026/02/cheudjeu_review_summary.html 

This document is the verbatim output from a structured, multi-stage debate conducted in February 2026 with Claude (Anthropic AI) regarding my three core peer-reviewed publications (PMC7443215, PMC8046744, PMC8954261) and one preprint (ResearchSquare rs-2899786).

  • Claude began with skeptical initial evaluations (6.5–7.5/10).

  • I responded using only existing peer-reviewed data and logical analysis.

  • Scores were subsequently revised upward (final: 9.5–10/10) based on resolution of specific objections, logical contradictions, and independent predictive elements (e.g., keratan sulfate selectivity, D-xylose metabolomics).

What this represents:
A transparent record of structured stress-testing through objection → rebuttal → reassessment.

It is not formal peer review and should not be interpreted as independent scientific validation. The purpose is methodological transparency — documenting how the framework responds to sustained critical examination.

For non-experts:
The work challenges the conventional assumption that cell-surface heparan sulfate (HS) promotes viral infection. Instead, it proposes that viruses dock at the serine attachment sites where HS chains initiate. This framework offers a unified explanation for:

  • Why heparin and D-xylose inhibit viral entry

  • Why certain sulfated GAGs (e.g., keratan sulfate) behave differently

  • Why viral infections can coincide with rising blood glucose and increased type 2 diabetes risk

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Extract from Vishnu C Ramani et al. paper (PMID: 22298773): “”Reducing the amount of heparan sulfate present on syndecan core proteins increases shedding of the ectodomain.””

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Table 3. Alterations in proteoglycan core proteins and heparanase in various cancers, and their reported associations with Type 2 diabetes.
Type of cancer Changes of core proteins Heparanase at cell surface (HPSE) Association with Type 2 Diabetes
Liver carcinoma Glypican-3 is overexpressed in hepatocellular carcinoma [42]. Syndecan-1 increased in liver dysfunction in HVC hepatocellular carcinoma [43] Overexpression of heparanase (2 fold) [44] There is a strong association between hepatocellular carcinoma and Type 2 Diabetes [45–47]
Lung cancer Excessive shedding of syndecan-1 is associated with higher-grade cancers and worse clinical prognosis [48]. Overexpression of heparanase [49] Pre-existing diabetes increase the risk of mortality amount Type 2 diabetes patients, especially women [50–52]
Colon cancer/ Colorectal cancer Upregulation of syndecan-2 [53] and decrease of syndecan-1 [54] correlation between heparanase expression and serosal invasion [54,55] Type 2 Diabetes increase the risk of colorectal cancer [56–58]
Breast cancer Upregulation of syndecan-1,  Syndecan-2 and Syndecan-4 is observed during Breast cancer and is correlates with poor prognosis and aggressive phenotype [59–61]. Overexpression of heparanase [62] Type 2 Diabetes increase the risk of Breast cancer [63–65]
Prostate cancer Syndecan-2 and syndecan-1 are overexpressed during prostate cancer and is associated with poor prognosis [66,67] Overexpression of heparanase [68] Type 2 Diabetes increase the risk of prostate cancer [69–71]
Skin cancer Upregulation of syndecan-2 [72] upregulation of heparanase which exerts protumorigenic properties [73] Type 2 Diabetes increase the risk of Skin cancer [74,75]
Pancreatic Cancer Upregulation of syndecan-2 [76] Overexpression of heparanase [77] Type 2 Diabetes increase the risk of Pancreatic cancer [78–81]
Ovarian Cancer Altered expression of syndecan-1 and perlecan [82] Overexpression of heparanase [83] Type 2 Diabetes increase the risk of Ovarian cancer [84,85]
Brain Cancer Upregulation of syndecan-1 [86] Overexpression of heparanase [87,88]
Oesophagial Cancer Loss of syndecan-1 [89] Overexpression of heparanase [89] Type 2 Diabetes increase the risk of Oesophagial  cancer [90,91]

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Based on the table above and Cheudjeu (2021): cancer cells have more available (free) cell-surface viral receptors (HS attachment sites) than normal cells. (This implies that viruses bind more easily to cancer cells, but not that they preferentially target cancer cells compared to normal cells.)

Ramini et al.’s results, together with the table above, suggest that stimulation of heparan sulfate (HS) biosynthesis may represent an anti-cancer strategy, notably through D-xylose, as supported by Wu et al.’s results.

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Just a reminder 🙂 : It’s not a coincidence

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——–//Dystroglycan… xylose…//

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Among 15 195 mouse serum metabolites analyzed, 670 were accurately identified, and 49 showed significant changes with both RSV infection and Feining mixture treatment. D-Xylose was among these 49 key metabolites, showing a significant decrease in RSV-infected mice and restoration toward normal levels after treatment. https://doi.org/10.1111/bcpt.70114

Table 1. Cross-disciplinary recent studies implicating D-xylose in disease severity and immune modulation. Summary of key studies from virology, metabolic disease, fibrosis, and cancer that identify D-xylose as an important metabolite.

Paper Key Molecule(s) Method # Metabolics/ molecules Screened Associated Disease Key Findings  Proportion of important Metabolites
Wu et al. (2025) Med (Cell Press) [15] D-xylose Metabolic gene screening (bioinformatics)+In vivo validation 1,660 metabolic genes Triple-negative breast cancer (TNBC) D-xylose depletion by DHDH suppresses immune response; D-xylose supplementation restores CD8+ T cell activity and reduces tumor growth 21 metabolic genes that were highly expressed, one of the top five being the DHDH
Yang et al. (2025) Frontiers in Pharmacology [16] D-xylose UHPLC-MS/MS; before and after administration of Rosa roxburghii Tratt juice (RRTJ) 1,264 plasma metabolites Arsenicosis patients (metabolic disorder in arsenicosis patients) Rosa roxburghii Tratt juice (RRTJ) intervention in arsenicosis patients resulted in significant modulation of 61 metabolites, with 30 upregulated and 31 downregulated. Among the upregulated metabolites, D-xylose and 2-isopropylmalate were specifically highlighted for their anti-inflammatory properties. The results induced the researchers to conclude that the anti-inflammatory property of RRTJ can be attributed to 2 metabolites only.
Reungoat Thesis (2018) [17] D-xylose Molecular/cellular assays N/A (targeted study) Hepatitis C virus (HCV) infection and liver fibrosis One key finding is a decrease in D-xylose levels within infected cells. This D-xylose deficiency correlates with disrupted biosynthetic pathways and impaired cellular communication. D-xylose deficiency disrupts GAG biosynthesis and contributes to fibrosis, a precursor to liver cancer All the alterations were correlated with only the level of xylose;
Sertbas & Ulgen (2024) ACS Publications [14] D-xylose Genome-scale metabolic model (GEM) 2,434 genes / 5,851 metabolites COVID-19 (SARS-CoV-2 liver infection)  D-xylose is identified as a promising metabolic supplement that may help counteract SARS-CoV-2 infection. Using genome-scale metabolic models of infected liver cells, the researchers found that D-xylose supplementation reduced the virus’s ability to replicate by interfering with the metabolic pathways it hijacks for its own reproduction. suggesting that D-xylose could support therapeutic strategies aimed at restoring healthy metabolism and limiting viral propagation. Among the 7 key metabolites identified, D-xylose was highlighted for its ability to reduce viral replication while preserving liver cell metabolism.
Baiges-Gaya et al. (2023) Biomolecules(MDPI) [13] Xylitol (sugar alcohol form of   D-xylose) GC-MS + Machine Learning Probably thousands (not specified) – 85 were selected for machine learning analysis. COVID-19 (hospitalized patients) Xylitol has been identified in this study as a key metabolite in the pentose and glucuronate interconversion pathway, which was found to be significantly upregulated in COVID-19-positive patients. Lower xylitol levels were associated with greater disease severity, especially in patients admitted to the ICU. Xylitol was among the top 5 Serum Metabolites Discriminating COVID-19-Positive Patients (vs. Healthy Controls).
Zheng et al. (2021) CSBJ (Elsevier) [12] D-xylose LC-MS + GC-MS From 2,698 identified metabolite peaks, 2,022 were selected for machine learning analysis. COVID-19 (non-severe cases) D-xylose among carbohydrates decreased during acute phase; recovery phase showed metabolic restoration D-xylose among the Approximately 5 metabolites, (in female patients), which have a very strong correlation with lung function parameters.
Pol & Mars (2021) Food & Nutrition Research (FNR) [18] D-xylose Human RCT (postprandial glucose & insulin) 2 (D-xylose, L-arabinose) Type 2 Diabetes (glycemic control) D-xylose added to sucrose-rich drinks significantly lowered postprandial glucose and insulin peaks vs control, indicating glycemic blunting effect. D-xylose demonstrated glycaemic and insulinaemic effects comparable to L-arabinose
 

Rosa roxburghii Tratt juice ameliorates metabolic disorder in arsenicosis patients based on the analysis of untargeted plasma metabolomics

Summary of findings about D-xylose by ChatGPT: D-xylose or a modified-D-xylose will replace insulin for Type 1 and Type 2 diabetes treatment. It’s just a matter of time. https://foodandnutritionresearch.net/index.php/fnr/article/view/6254/13751 “Results:Glucose and insulin peaks were lower after the L-arabinose and D-xylose drink than the control drink(P< 0.01).” https://pulp2value.eu/media/2020/03/Poster-SSIB-2018_v4-20200306.pdf 
https://e-nrp.org/DOIx.php?id=10.4162/nrp.2016.10.1.11
"RESULTS
In vivo, D-xylose supplementation significantly reduced fasting serum glucose levels (P < 0.05), it slightly reduced the area under the glucose curve, and increased insulin levels compared to the diabetic controls. D-Xylose supplementation enhanced the regeneration of pancreas tissue and improved the arrangement of hepatocytes compared to the diabetic controls.” 
A study on antimicrobial effect of sugars at low concentration
Extract:
"Xylose inhibited growth of nine Gram-positive (one isolate each of Enterococcus faecium, E. raffinosus, G. stearothermophilus, Mammaliicoccus 
sciuri, Paenibacillus macerans, P. alvei, P. amylolyticus, Staphylococcus caseolyticus and Staphylococcus delphini) and one C. freundii 
(a Gram-negative bacterium) isolates (Table 2)"
Huai-liang Wu et al. “””
  • D-xylose promotes immune infiltration via upregulation of PSMB9
  • D-xylose supplementation potentiates the efficacy of immunotherapy in TNBC “”””
https://www.cell.com/med/abstract/S2666-6340(24)00410-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2666634024004100%3Fshowall%3Dtrue    **************** FUTURE PROJECTS  *************
  1. Chemical modification of D-xylose to improve its antiviral properties against dozens of viruses e.g., Artificial 2-O-Phosphorylation of D-Xylose
  2. Artificial 2-O-Phosphorylation of D-Xylose and GAG biosynthesis
  3. Chemical modification (methylation ?…) of D-xylose-2-phosphate  for blood-brain barrier crossing → potential for brain disease treatment
  4. Synthesis of a D-xylose-modified drug with a molecular weight at least 10 times lower than that of enoxaparin but with the same efficacy
  5. Viruses and P53 mutations: glycosylation, hydroxyl group (-OH) of Ser/Threonine residues, post-translational modifications (PTMs) positioning
  6. D-xylose-modified drug for cancer treatment
**** I’m now a member of : ASBMB : American Society for Biochemistry and Molecular Biology ***   The first patent application is now online: https://data.inpi.fr/brevets/FR3142656   A third study published in ACS confirms the correlation between COVID-19 severity and D-xylose level. In addition, the study shows that D-xylose has antiviral properties… “Computational analysis also showed that administration of dopamine, glucosamine, D-xylose, cysteine, and (R)-3-hydroxybutanoate contributes to alleviating viral infection. ” https://pubs.acs.org/doi/10.1021/acsomega.4c00392     Excellent reference: https://portlandpress.com/biochemj/article-abstract/148/1/25/9242/The-effect-of-D-xylose-D-xylosides-and-D “The incorporation of [3H]acetate into chondroitin sulphate was used as a measure of the rate of synthesis of this polysaccharide in whole tibias and femurs of embryonic chicken cartilage in vitro. The incorporation is inhibited by puromycin and by cycloheximide, but the inhibition is relieved by the addition of D-xylose, xβ-D-xylosides and β-D-galactosides to the incubation medium. β-D-Xylosides can stimulate the incorporation to 300% of that of controls incubated in the absence of cycloheximide or puromycin, D-Xylose, β-D-xylosides and β-D-galactosides appear to act as artificial initiators of chondroitin sulphate synthesis and enable polysaccharide-chain synthesis to be studied as an event separate from the synthesis of intact proteoglycan.”   The effect of beta-D-xylosides on the proliferation and proteoglycan biosynthesis of monoblastic U-937 cells :

“Abstract

The monoblastic cell line U-937 was cultured in the presence of C-ethyl beta-D-xyloside (E-xyl), hexyl beta-D-thioxyloside (HX-xyl), p-nitrophenyl beta-D-xyloside, phenyl beta-D-xyloside or phenyl alpha-D-xyloside. All of the beta-D-xylosides inhibited proliferation, but HX-xyl was by far the most efficient, and had a maximum effect at 1 mM concentration. ” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1133682/ 

This CONCENTRATION OF 1mM is the target of my ongoing project.   From Fulgentius N. Lugemwa and Jeffrey D. Esko paper, 1990: https://www.sciencedirect.com/science/article/pii/S0021925820895490                                    Updated version Under Review: D-Xylose, a Stimulator of Heparan Sulfate Biosynthesis, Exhibits Antiviral Properties Against SARS-CoV-2, ZIKV, HCMV and HIV-1 NL4-3 In Vitro     Extract from OSWALD WILSON et al.                         https://www.ncbi.nlm.nih.gov/research/coronavirus/publication/37292550  “”We are reporting a two-year and nine-month-old boy who had a coronavirus disease (COVID) infection and then presented with a refusal to walk. By careful history-taking, he was found to have a restricted diet, speech delay, and gum bleeding suggestive of scurvy, which was confirmed by extremely low levels of ascorbic acid. In this case, the diagnosis of scurvy was established before establishing the diagnosis of neurodevelopmental delay. Treatment with ascorbic acid resulted in a remarkable improvement in his symptoms.”””   Vitamin C  —> D-xylose  —–> CS biosynthesis —-> Cartilage….

The SARS-CoV-2 Entry Inhibition Mechanisms of Serine Protease Inhibitors, OM-85, Heparin and Soluble HS Might Be Linked to HS Attachment Sites

Table 3 shows that the largest contributor by far to the mass of GAGs having D-xylose as a binding element on core proteins is the cartilage, with about 70 g of chondroitin sulfate. What is the impact of COVID-19 or type 2 diabetes on cartilage? Studies reported the inflammation of arthritis in the pathobiology of COVID-19 [86]. However, in 1987, Kleesiek et al. [87], in an in vivo study, showed that the serum of xylosyltransferase, which catalyses the transfer of D-xylose from UDP-xylose to the hydroxyl group of serine residues of core proteins, was a biomarker of cartilage destruction in chronic joint disease [87]. Preprint: D-Xylose, a Stimulator of Heparan Sulfate Biosynthesis, Exhibits Antiviral Properties Against SARS-CoV-2, ZIKV, HCMV and HIV-1 NL4-3 In Vitro https://doi.org/10.21203/rs.3.rs-2899786/v1
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Extract from Kaji and N S paper:
 
    Thus, Trindade et al paper confirm this speculation of Kaji and NS.   UFH binds at HS attachment site , But not LMWH due to the compound added on the anomeric C of D-xylose of the latter.   Entry into the cell by endocytosis of viruses that use PGs as receptors: Just the fact that these viruses bind to PGs is sufficient. In fact, Yanagishita, M. (J. Biol. Chem. 1992) showed that, between 70% and 100% of PGs shed from the cell surface are endocytosed. Thus, independent of the viral binding sites of these viruses on PGs, the viruses are endocytosed with PG during the renewal process of the latter.
  • Yanagishita, M. (J. Biol. Chem. 1992) + Christianson and Belting (Matrix Biol., 35 (2014), pp. 51-55)  papers  ≡ All endocytosis and exocytosis routes of viruses that use PGs as receptors are just consequences of PGs renewable process.
Yanagishita, M. (J. Biol. Chem. 1992): extract                            Figure 1. of Naomi Veraldi et al., Figure 1. Schematic model of heparan sulfate proteoglycans and heparanase trafficking. About clathrin- and caveolin-independent pathways Payne et al, paper (Original R. paper):

Internalization and Trafficking of Cell Surface Proteoglycans and Proteoglycan-Binding Ligands

            ***************************************************** Lars-Åke Fransson et al, 1992  
Same conclusions as
– Nader et al,
– Trindade et al ,
– Kaji and Sakuragawa
***************************************************************************** A team of researchers, clinicians, have just confirmed the correlation between the serum level of xylitol and the severity of COVID-19. Like the team of Zheng et al, they determined the metabolites in the serums of COVID-19 patients and controls. And used artificial intelligence to determine the 5 metabolites ( maltose, glyceric acid, mannonic acid, xylitol, and erythronic acid ) whose variations are correlated with the severity of COVID-19. Link:Gerard Baiges-Gaya et al, Combining Semi-targeted Metabolomics and Machine Learning to Identify Metabolic Alterations in Serum and Urine of Hospitalized Patients with COVID-19               Main conclusion of this paper: “” In addition, patients who needed intensive care had lower xylitol concentrations than those who did not.“” Very happy with these results 🙂 Link to Zheng et al paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021501/ Any link between Baiges-Gaya et al versus Zheng et al metabolites ? -> Yes Xylose <–> Xylitol  Rereading the preprint of Baiges-Gaya et al, makes me even more admiring of their study. Indeed, after the publication of Zheng et al’s paper, I had been lucky enough to have been solicited a few months before by the same journal for a paper, so I had jumped at the opportunity by writing a “Highlights ” (the journal not publishing a letter to the Editor). In this 2-page Highlights, I explained why the interpretation of Zheng et al on the decrease in serum level D-xylose after discharge was not consensual. I had concluded with a small table (see below). Essentially, Zheng et al concluded that, despite the correlation between the severity of Covid-19 and the level of D-xylose, they did not recommend supplementing patients with D-xylose because they found that the level of D-xylose was reduced after discharge.
Baiges-Gaya et al, although they did find that xylitol levels were higher in COVID patients compared to the control group (without COVID), they did the right comparison (exactly as I proposed in that unpublished highlights): they have compared the level of xylitol for severe cases and non severe cases! It’s Excellent!  It’s a matter of competitive inhibition.
(concerning the highlights : After two months without a first decision, the journal implicitly suggested that I withdraw my paper…. I inserted it in my 3rd paper almost a year later…).
Extract of the highlights:

“”Finally, as summarized in Table 1, to ultimately validate or invalidate this therapeutic pathway, a comparison should be made between the mean value of the amount of D-xylose in the plasma of patients with severe COVID-19 and the same value in patients with nonsevere COVID-19 (at the same stage). This approach is what we previously proposed in August 2020 at the conclusion of paper [2].

Since Zheng et al have reported greater severity of COVID-19 in male patients compared to female patients [1], a comparison of the mean value of the amount of D-xylose of both groups can provide a clear indication (see Table 1).

Table 1: D-Xylose changes between the acute period and follow-up period and the Zheng et al results and comparison needed for validation.

Acute period: AP

Follow-up period: FP

Zheng et al results

Group 1 :  Female patients

– D-xylose level in the plasma: q1-AP – Degradation of HS chains due to binding of viruses at HS attachment sites → Inflammation and injury / increase in the plasma of sugars used for HS chains (including xylose)

– D-xylose level in the plasma: q1-FP   – Biosynthesis of HS chains due to reduction of viral load → reduction of inflammation and injury / decrease in the plasma of sugars used for HS chains (including xylose)

Zheng et al results have reported reduction of the  D-xylose level in the plasma after discharge: q1-FP < q1-AP . This is the consequence of HS biosynthesis induced by the reduction of viral load.

Group 2:        Male patients

– D-xylose level in the plasma: q2-AP – Degradation of HS chains due to binding of viruses at HS attachment sites → Inflammation and injury / increase in the plasma of sugars used for HS chains (including xylose) – More serious organ injuries in men compared with women

– D-xylose level in the plasma: q2-FP   – Biosynthesis of HS chains due to reduction of viral load → reduction of inflammation and injury / decrease in the plasma of sugars used for HS chains (including xylose)

D-xylose was not an important metabolite in the male group 

D-xylose supplementation for COVID-19 and other viral infections using core proteins as receptors at cell surface 

  Since, Zheng et al [1] have confirmed that the changes of D-xylose correlates with lung function parameters, a comparison should be made between the mean value of the amount of D-xylose in the plasma of patients with severe COVID-19 and the same value in patients with nonsevere COVID-19 (at the same stage): q2-AP Vs q1-AP  or q2-FP  Vs q1-FP 
 

In addition, Zheng et al [1] reported that a higher level of dehydroascorbic acid (DAA) was linked with a reduction in the levels of inflammation markers. Moreover, we have shown in section 9 (Figure 1) of the same paper [2] that D-xylose is a metabolite of DAA.

We highlight here that D-xylose has antiglycemic, anti-inflammatory and antiviral properties, is safe and is already used for the “D-xylose test” [2].“””

  ************************ In vitro 1991 Antibacterial activity of D-xylose