bims-supasi 2025-09-07 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2025–09–07
sixteen papers selected by
Jonathan Wolf Mueller, University of Birmingham

Congenital disorders caused by aberrations in the biosynthesis of chondroitin/dermatan sulfate.
Marine-derived sulfated glycans display a potent virostatic mechanism to block herpes simplex virus type-1 (HSV-1) entry and spread.
Effects of 25-hydroxyvitamin D3, chondroitin sulfate and glucosamine sulfate on the growth performance, calcium and phosphorus metabolism, and bone development of weaned piglets.
Production of chondroitin by Corynebacterium glutamicum through co-utilization of glucose and xylose from corn straw.
Albumin Nanocages with Methotrexate and Chondroitin Sulfate as a Dual pH/GSH-Responsive Tumor Targeting Nanomedicine for Synergistic Cancer Therapy.
L-Carnosine Loaded Chondroitin Sulphate Functionalized Proposomes as an Effective Tool for Transdermal Rheumatoid Arthritis Management.
Progress on the synthesis of bioengineered heparin as an alternative to animal-derived heparin active pharmaceutical ingredient.
Dehydroepiandrosterone Sulfate in Diagnosing Mild Autonomous Cortisol Secretion and Adrenal Insufficiency.
An ancient and essential miRNA family controls cellular interaction pathways in C. elegans.
The Pathophysiological Functions of Heparanases: From Evolution, Structural and Tissue-Specific Perspectives.
Deletion of sulfate transporter SUL1 extends yeast replicative lifespan via reduced PKA signaling instead of decreased sulfate uptake.
Mass spectrometry and enzyme assays refute histone tyrosine sulfation.
Enhanced sleep quality and reduced indoxyl sulfate levels following probiotic supplementation were linked to gut microbiota modulation in hemodialysis patients.
Clinical Utility of Salivary Steroid Profiling for the Differential Diagnosis of Adrenal Diseases.
Reduced heparan sulfate levels in cerebrospinal fluid reflect brain neuron correction in Sanfilippo B mice.
Hormonal contraceptive use in relation to basal and reactive testosterone, DHEAS, and cortisol.

J Hum Genet. 2025 Sep 02.

Congenital disorders caused by aberrations in the biosynthesis of chondroitin/dermatan sulfate.

Tadahisa Mikami, Shuji Mizumoto, Hiroshi Kitagawa, Shuhei Yamada.

Chondroitin sulfate (CS)/dermatan sulfate (DS) proteoglycans that play indispensable roles in multiple physiological processes, including cell proliferation, cell adhesion, development, neuronal guidance, and cartilage formation. Depletion of CS/DS caused by biosynthetic enzyme loss of function impairs these processes and results in embryonic lethality. However, some individuals with mutant enzymes survive and exhibit severe phenotypes. These rare hereditary diseases have been discovered and characterized in recent decades because of marked advances in next-generation sequencing technology. In this review, CS/DS-related inherited diseases caused by aberrations in both CS/DS backbone synthesis, as well as their sulfation and/or epimerization, are comprehensively summarized and their pathogenesis discussed.

DOI: https://doi.org/10.1038/s10038-025-01396-0
Carbohydr Polym. 2025 Nov 15. pii: S0144-8617(25)00926-9. [Epub ahead of print]368(Pt 1): 124141

Marine-derived sulfated glycans display a potent virostatic mechanism to block herpes simplex virus type-1 (HSV-1) entry and spread.

James Elste, Michele Rabbitt, Chunyu Wang, Jonathan S Dordick, Vaibhav Tiwari, Fuming Zhang.

  A naturally derived library of glycomimetic mimicking the structure-function of heparan sulfate (HS) remains an untapped reservoir for drug discovery against viral infections. In this work we screened a library of marine-derived sulfated glycans from seaweeds and sea cucumbers to investigate if they can compete for the ligand/receptor binding sites to prevent virus entry. Multiple promising candidates were identified, such as RPI-27 (IC50: 1.51 μM), FCS-Pg (IC50: 0.906 μM), FCS-Ib (IC50: 0.725 μM), and Rhamnan sulfate (RS; IC50: 0.499 μM) capable of preventing HSV-1 entry at non-toxic concentrations when pre-incubated with the target cells before infection. Interestingly, we noticed a significant improvement in the IC50 values among the sulfated glycans [RPI-27 (IC50: 0.008 μM), FCS-Pg (IC50: 0.007 μM), FCS-Ib (IC50: 0.003 μM), and RS (IC50: 0.004 μM)] when they were pre-exposed to the virus before infecting to the target cell. The Surface Plasmon Resonance (SPR) spectroscopy established the library's efficacy for their high binding affinity for HSV-1 central envelope glycoprotein D (gD), implying the potent virostatic nature of the sulfated glycans. These findings offer a rationalized development of targeted and fine-tuned marine-derived carbohydrate-based molecules to prevent HSV-1 entry and virus replication using either prophylaxis and or treatment approaches.

Keywords:  Heparin; Herpes simplex virus; Marine sulfated glycans; Surface plasmon resonance

DOI:  https://doi.org/10.1016/j.carbpol.2025.124141
Anim Nutr. 2025 Sep;22 459-470

Effects of 25-hydroxyvitamin D3, chondroitin sulfate and glucosamine sulfate on the growth performance, calcium and phosphorus metabolism, and bone development of weaned piglets.

Yuyue Xi, Baoshi Shi, Xutong Guo, Wenxue Li, Zhiru Tang, Qingsong Tang, Yetong Xu, Xie Peng, Zhihong Sun.

  This study aimed to determine the effects of 25-hydroxyvitamin D3 (25-OH-VD3), combined with chondroitin sulfate (CS) and glucosamine sulfate (GS), on calcium and phosphorus metabolism and bone development of weaned piglets. One hundred weaned piglets (28 d old; Duroc × Landrace × Large White; initial body weight, 7.8 ± 0.22 kg) were randomly assigned to 5 dietary treatments, which included basal diet + 50 μg/kg vitamin D3 (CON), basal diet + 50 μg/kg 25-OH-VD3 (HyD), basal diet + 50 μg/kg 25-OH-VD3 + 800 mg/kg CS (CS), basal diet + 50 μg/kg 25-OH-VD3 + 1200 mg/kg GS (GS), and basal diet + 50 μg/kg 25-OH-VD3 + 800 mg/kg CS + 1200 mg/kg GS (CS + GS). The experiment lasted 31 d, including 3 d of acclimation. The results showed that pigs in the HyD and GS groups had a higher (P = 0.006) apparent digestibility of calcium than pigs in the CON group. The bone mineral density and calcium content in the metatarsal and phalangeal bones of piglets in the CS and GS groups were significantly higher (P < 0.05) than those in the CON and HyD groups. The mRNA expression of transient receptor potential cation channel subfamily V member 6 and calcium-binding protein D9K in the colon mucosa and transient receptor potential cation channel subfamily V member 5, solute carrier family 34 member 1, calcium-sensing receptor, and calcium-binding protein D28K in the kidneys of piglets was upregulated (P < 0.05) in the GS group compared to that in the CON, HyD, CS, and CS + GS groups. The protein expression of cytochrome P450 27B1 and calcium-sensing receptor in the kidneys of piglets was upregulated (P < 0.05) in the GS group compared to that in the CON, HyD, and CS + GS groups. Overall, dietary supplementation with 25-OH-VD3 alone or in combination with GS enhanced bone development in piglets by improving calcium and phosphorus metabolism.

Keywords:  25-Hydroxyvitamin D3; Calcium and phosphorus metabolism; Chondroitin sulfate; Glucosamine sulfate; Weaned piglet

DOI:  https://doi.org/10.1016/j.aninu.2024.12.009
Int J Biol Macromol. 2025 Sep 03. pii: S0141-8130(25)07949-8. [Epub ahead of print] 147392

Production of chondroitin by Corynebacterium glutamicum through co-utilization of glucose and xylose from corn straw.

Zhuangzhuang Shi, Yue Ming, Jue Li, Yufei Zhao, Weilong Wang, Wei Sha, Guoqiang Li, Mengmeng Wu, Ting Ma.

  Chondroitin sulfate (CS), a biopolymer with critical applications in osteoarthritis treatment and biomedical sectors, faces production challenges due to low yields and high costs. This study established a high-yield chondroitin (the major precursor of CS) production platform in Corynebacterium glutamicum for the simultaneous utilization of glucose and xylose from corn straw hydrolysate. Firstly, through codon optimization of genes encoding chondroitin synthase (KfoC) and UDP-N-acetylglucosamine-4-epimerase (KfoA), combined with tailoring metabolic pathways and medium components for chondroitin synthesis, yielded the high-titer strain CgC25. Fed-batch fermentation achieved a chondroitin titer of 9.59 ± 0.15 g/L in CgC25, the highest reported titer for medium molecular weight chondroitin to date. Next, the xylose metabolism module was optimized by reconstructing the xylose isomerase (XI) and Weimberg pathways using an RBS-library strategy, ultimately yielding a strain CgRXIW. Finally, integration of xylose metabolism and chondroitin synthesis modules enabled CgC25 to produce 6.64 ± 0.11 g/L chondroitin from corn stover hydrolysate. Integration of the xylose metabolism pathway with chondroitin synthesis modules enabled. This study establishes a glucose and xylose co-utilization mechanism in C. glutamicum, offering a scalable platform for cost-effective chondroitin production and the biosynthesis of high-value compounds from renewable feedstocks.

Keywords:  C. glutamicum; Chondroitin; Synergetic utilization

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.147392
Biomater Res. 2025 ;29 0245

Albumin Nanocages with Methotrexate and Chondroitin Sulfate as a Dual pH/GSH-Responsive Tumor Targeting Nanomedicine for Synergistic Cancer Therapy.

Haroon Iqbal, Anam Razzaq, Ziyin Yuan, Lina Zhai, Yue Wang, Uzair Ur-Rehman, Lv Man, Jun Xin, Xin Ning, Yuanbo Liang, Run Xiao.

Cancer is a devastating disease, and its pathogenesis is highly associated with malnutrition and poor lifestyle. Chemotherapy continuously causes inadequate therapeutic efficacy and induces off-target toxicities. Hence, targeted co-administration of chemotherapy and dietary supplement producing anticancer effect at low doses with minimized toxicities would be a promising strategy for cancer treatment. In this study, we constructed chondroitin sulfate (CS) and methotrexate (MTX) carried serum albumin nanocages (C/M@Alb NCs) by albumin nanoreactor strategy. During fabrication, we achieved the precipitation of MTX and CS inside the albumin nanocore under mild reaction condition to prepare C/M@Alb NCs. The enhanced anticancer efficacy of C/M@Alb NCs was comprehensively assessed by in vitro and in vivo experiments. Biodistribution, pharmacokinetic profile, and in vivo therapeutic efficacy of C/M@Alb NCs were investigated in human colorectal adenocarcinoma (HT-29), murine breast cancer (E0071), and patient-derived (PDX) lung cancer models. The as-prepared C/M@Alb NCs facilitated higher MTX and CS encapsulation, exhibiting small particle size, improved colloidal stability, dual stimuli (pH/GSH)-responsive drug release profile, an enhanced cellular uptake, cooperative synergistic cytotoxicity, extended blood residence time, improved lymph node and tumor targeting, and in vivo therapeutic efficacy against various cancers such as human colorectal adenocarcinoma, murine breast cancer, and patient-derived (PDX) lung cancer. Altogether, C/M@Alb NCs exhibited enhanced cellular uptake, extended blood residence time, and favorable tumor accumulation and lymph node extravasation, finally leading to the potent antitumor efficacy against various cancers. This nanoplatform offers a new strategy for designing lymph node- and cancer-targeted albumin-based nanomedicine for clinical applications.

DOI: https://doi.org/10.34133/bmr.0245
J Drug Target. 2025 Sep 04. 1-22

L-Carnosine Loaded Chondroitin Sulphate Functionalized Proposomes as an Effective Tool for Transdermal Rheumatoid Arthritis Management.

Mariam Zewail, Haidy Abbas, HussamElDin Y Aboukilila, Mai F Ragab, Miranda F Kamal, Passent M E Gaafar.

  Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes joint inflammation, cartilage deterioration, and oxidative stress. The study developed transdermal RA treatment with L-carnosine (CAR)-loaded chondroitin sulfate (CHS) functionalized proposomes. CHS-functionalized proposomes measured 285 ± 0.89 nm, with PDI of 0.31 ± 0.05, zeta potential of -13.6 ± 0.67 mV, and entrapment efficiency of 73.96 ± 0.87. TEM confirmed their spherical shape and homogenous CHS coating. Biphasic drug release in vitro began with 13.2% burst release in 0.5 h and over 8 h, sustained release reached 83.79%. Ex-vivo permeation results revealed that F5 increased CAR flux by 30.97 folds compared to CAR gel. In vivo testing in rats with AIA model showed that group treated with selected formulation demonstrated reduced joint inflammation and soft tissue swelling that was further confirmed by X-ray radiography. ELISA results showed significant reduction in TNF-α and IL-1β and elevation in NRF2 and SOD with levels comparable to the negative control group. Histopathological investigation showed cartilage integrity and proteoglycan content similar to the negative control. The CHS-functionalized CAR-loaded proposomes improved CAR permeation, targeted inflammatory joints, and reduced oxidative stress, making them a viable non-invasive RA treatment.

Keywords:  Autoimmune diseases; Carnosine; Chondroitin Sulphate; Liposomes; Non-invasive routes; Penetration enhancers

DOI:  https://doi.org/10.1080/1061186X.2025.2557465
Carbohydr Polym. 2025 Nov 15. pii: S0144-8617(25)00884-7. [Epub ahead of print]368(Pt 1): 124099

Progress on the synthesis of bioengineered heparin as an alternative to animal-derived heparin active pharmaceutical ingredient.

Xiaohan Jiang, Bo Zhang, Xue Cai, Zhiqiang Liu, Yuguo Zheng.

  Heparin, a clinically essential anticoagulant, has long been derived from animal sources, posing risks of contamination and supply chain instability. Bioengineered heparin, synthesized via microbial fermentation and enzymatic modification, offers a promising alternative with enhanced safety, homogeneity, and scalability. This review highlights recent advances in heparosan biosynthesis, enzymatic sulfation strategies, and analytical characterization for bioengineered heparin. Critical challenges remain, including precise control of heparosan molecular weight, optimization of sulfation patterns, demonstration of structural and functional equivalence to animal-derived heparin, and industrial-scale process validation. By combining synthetic biology with advanced bioprocessing and quality control, structure-defined bioengineered heparin is poised to become a sustainable, high-performance replacement for traditional heparin active pharmaceutical ingredient (API).

Keywords:  Bioengineered heparin; Heparosan; Microbial-enzymatic synthesis; Molecular weight control; Quality control; Sulfation modification

DOI:  https://doi.org/10.1016/j.carbpol.2025.124099
J Endocr Soc. 2025 Sep;9(9): bvaf136

Dehydroepiandrosterone Sulfate in Diagnosing Mild Autonomous Cortisol Secretion and Adrenal Insufficiency.

Jasmine Saini, Bahaa Salama, Kai Yu, Shireen R Chacko, Ashley J Han, Camila Villavicencio Torres, Mohammad Hassan Murad, Irina Bancos.

   Context: Data on diagnostic accuracy of dehydroepiandrosterone sulfate (DHEA-S) for mild autonomous cortisol secretion (MACS) and adrenal insufficiency (AI) are discrepant.
Objective: We conducted a systematic review and meta-analysis of published studies assessing the accuracy of DHEA-S in diagnosing MACS or AI.
Methods: From inception to January 8, 2024, we searched databases for original studies of at least 20 participants with MACS or AI. MACS was defined as postdexamethasone cortisol greater than 1.8 mcg/dL or postsurgical hypocortisolism. AI was defined by abnormal dynamic testing. QUADAS-2 was used to assess the risk of bias. Bivariate random effects meta-analysis was used to generate pooled diagnostic accuracy estimates.
Results: Seven studies on DHEA-S accuracy in diagnosing MACS (574 patients with MACS, 830 referent individuals), and 2 studies on DHEA-S accuracy in diagnosing AI (52 patients with AI, 59 referent individuals) were included. A meta-analysis of studies using DHEA-S cutoff between 60 and 70 mcg/dL to diagnose MACS demonstrated a sensitivity of 82% (95% CI, 64%-93%) and a specificity of 82% (95% CI, 74%-88%). In the 2 studies evaluating DHEA-S in diagnosing AI, the reference standard was a 1-mcg cosyntropin stimulation test. The sensitivity of DHEA-S for diagnosing AI ranged from 70.3% to 86.7%, and the specificity was 87.1%. Most studies were at a moderate risk of bias.
Conclusion: Based on limited heterogeneous evidence, measurement of DHEA-S provides additional value in diagnosing MACS, as well as AI.

Keywords:  adrenal; cortisol; diagnosis; likelihood ratio; sensitivity; specificity

DOI:  https://doi.org/10.1210/jendso/bvaf136
Sci Adv. 2025 Sep 05. 11(36): eadz1934

An ancient and essential miRNA family controls cellular interaction pathways in C. elegans.

Emilio M Santillan, Eric D Cormack, Jingkui Wang, Micaela Rodriguez-Steube, Luisa Cochella.

The transition from unicellular to multicellular life required the acquisition of coordinated and regulated cellular behaviors, including adhesion and migration. In metazoans, this involves adhesion proteins, signaling systems, and an elaborate extracellular matrix (ECM) that contributes to adhesion and signaling interactions. Innovations that enabled complex multicellularity occurred through new genes in these pathways, novel functions for existing genes, and regulatory changes. Gene regulation by microRNAs (miRNAs) expanded with multicellularity. A single miRNA, miR-100, arose in the last common eumetazoan ancestor and is widely conserved across animals. We reveal the molecular function of its C. elegans homolog, the miR-51 family. This family acts in a dose-dependent manner to control morphogenesis by regulating several genes involved in cell signaling, adhesion, and migration, including ECM modifiers-specifically heparan sulfate sulfotransferases (HSTs). Some of these targets are also predicted to be conserved targets across vertebrates. Our work suggests that this miRNA provided an innovation in the regulation of cellular interactions early in metazoan evolution.

DOI: https://doi.org/10.1126/sciadv.adz1934
FASEB J. 2025 Sep 15. 39(17): e70976

The Pathophysiological Functions of Heparanases: From Evolution, Structural and Tissue-Specific Perspectives.

Elham Vahdatahar, Clément Daviaud, Hugo Main, Rachel Havret, Claire Debarnot, Laure Favot-Laforge, Jean-François Jégou, Ingrid Fruitier-Arnaudin, Antoine Dufour, Romain Vivès, Franck Morel, Yves Bourne, Kévin Baranger.

  Heparanase 1 (HPSE1) is a unique endoglycosidase responsible for the enzymatic cleavage of heparan sulfate, thereby playing important functions in cancer processes. In contrast, the structurally related Heparanase 2 (HPSE2) lacks catalytic activity and appears to counteract HPSE1 activities. However, contradictory observations in various pathologies highlight the need for a better understanding of the respective contributions of both heparanases. In this review, we provide a comprehensive resource about the biology of HPSE1 and HPSE2 based on findings from different mouse models, with an emphasis on immune cells and their involvement in skin pathophysiology. In addition, we explore the evolutionary relationships between the two heparanases and describe the structure-function of HPSE2 using the advanced protein-prediction tool AlphaFold 3 (AF3). These approaches unveil new insights for deciphering the functional molecular determinants that distinguish HPSE1 from HPSE2.

Keywords:  Heparanase; cancer; immune cell; molecular modeling; mouse model; skin inflammation

DOI:  https://doi.org/10.1096/fj.202501859R
Elife. 2025 Sep 03. pii: RP94609. [Epub ahead of print]13

Deletion of sulfate transporter SUL1 extends yeast replicative lifespan via reduced PKA signaling instead of decreased sulfate uptake.

Juan Long, Meng Ma, Yuting Chen, Bo Gong, Yi Zheng, Hao Li, Jing Yang.

  The regulation of cellular metabolism and growth in response to nutrient availability is crucial for cell survival and can significantly impact on lifespan. Central to this regulation is a class of transporters that sense and transport specific nutrients and transduce the signal downstream to control genes responsible for growth and survival. In this study, we identified SUL1, a plasma membrane transporter responsible for regulating the entry of extracellular sulfate in Saccharomyces cerevisiae, as a key gene for regulating lifespan. We conducted a systematic analysis to delineate the downstream mechanism underlying the lifespan extension by SUL1 deletion. Surprisingly, we found that the lifespan-extending effect of SUL1 deletion is not due to decreased sulfate transport. The SUL1 deletion mutant exhibited decreased PKA signaling, resulting in a series of downstream effects, including increased stress-protective trehalose and glycogen, increased nuclear translocation of MSN2, elevated expression of general stress response genes, enhanced autophagy, and reduced expression of amino acid biosynthetic and ribosomal genes. We demonstrated that the observed increase in lifespan is dependent on MSN2 and autophagy pathways. Our findings exemplify the influence of nutrient signaling rather than the nutrient itself on lifespan regulation and further substantiate the pivotal role of the PKA pathway in this process.

Keywords:  MSN2; PKA activity; S. cerevisiae; SUL1; cell biology; longevity; stress response

DOI:  https://doi.org/10.7554/eLife.94609
Nat Chem Biol. 2025 Sep 01.

Mass spectrometry and enzyme assays refute histone tyrosine sulfation.

Menatallah M Youssef, Carson W Szot, Miriam F Ayad, Lobna A Hussein, Maha F Abdel-Ghany, Ryan C Bailey, Ahmed M Mostafa, Kristina Hakansson.

DOI: https://doi.org/10.1038/s41589-025-01994-1
J Formos Med Assoc. 2025 Aug 27. pii: S0929-6646(25)00455-3. [Epub ahead of print]

Enhanced sleep quality and reduced indoxyl sulfate levels following probiotic supplementation were linked to gut microbiota modulation in hemodialysis patients.

Yi-Chun Wang, I-Jung Tsai, Tsung-Han Hsieh, Chia-Chao Wu, Kuo-Cheng Lu, Min-Tser Liao.

   OBJECTIVE: Hemodialysis patients frequently exhibit altered gut microbiota and elevated indoxyl sulfate (IS) levels, a uremic toxin linked to negative health outcomes. This study explores how probiotic supplementation may be associated with changes in uremic toxins and sleep quality in hemodialysis patients through its relationship with gut microbiota.
DESIGN AND METHODS: This open-label, randomized cohort study involved 80 hemodialysis patients with poor sleep quality, assessed by the Pittsburgh Sleep Quality Index (PSQI) Global Score. Participants were divided into two groups of 40. The probiotic group received two packs of freeze-dried Lactobacillus casei rhamnosus (Lcr35) daily for 12 weeks, while the control group received standard care. Baseline data, comorbidities, and blood samples were collected. Measurements included sleep quality (PSQI), uremic pruritus (5-D Itch Scale), heart rate variability, and plasma levels of IS and interleukin 6 (IL-6). Fecal samples were collected once before and once after probiotic treatment, and microbiota composition was assessed using 16S rRNA gene sequencing.
RESULTS: Probiotic treatment significantly lowered IS levels in the probiotic group from 69.89 ± 31.51 μg/mL to 62.37 ± 29.84 μg/mL (P < 0.005), with no significant changes in the control group. The probiotic group also saw an increase in sleep duration from 5.83 ± 1.63 h to 6.30 ± 1.31 h (P < 0.01), unlike the control group. Sleep quality, measured by the PSQI Global Score, improved significantly in the probiotic group compared to the control group (P < 0.05). No significant changes were observed in heart rate variability, 5-D Itch Scale, or IL-6 levels. Microbiota enrichment showed significant improvements post-probiotic intervention. Bifidobacterium, Oscillospira, and Nitrospira increased in abundance, whereas TG5 decreased. Both Bifidobacterium and Oscillospira were linked to better sleep quality Both Bifidobacterium and Oscillospira were associated with better sleep quality, while Nitrospira and reduced TG5 levels correlated with lower IS levels.
CONCLUSION: This study suggests that the reduction in indoxyl sulfate levels and the improvement in sleep quality following probiotic supplementation in hemodialysis patients may be linked to the modulation of gut microbiota.

Keywords:  Gut microbiota; Hemodialysis; Indoxyl sulfate; Probiotics

DOI:  https://doi.org/10.1016/j.jfma.2025.08.036
J Clin Endocrinol Metab. 2025 Sep 05. pii: dgaf499. [Epub ahead of print]

Clinical Utility of Salivary Steroid Profiling for the Differential Diagnosis of Adrenal Diseases.

Kyoung Yeun Jung, Soyeon Park, Chaelin Lee, Eu Jeong Ku, Sihoon Lee, Kyoung-Ah Kim, Sang Wan Kim, Yumie Rhee, Jung Soo Lim, Choon Hee Chung, Sung Wan Chun, Soon-Jib Yoo, Ohk-Hyun Ryu, Hochan Cho, A Ram Hong, Hyo-Jeong Kim, Man Ho Choi, Jung Hee Kim.

   CONTEXT: Although salivary steroid sampling offers several advantages, the diagnostic potential of salivary steroid metabolites remains largely unexplored.Objective To evaluate the diagnostic utility of salivary steroid profiling in patients with adrenal diseases.
DESIGN: Prospective multicenter study.
PATIENTS: Three hundred thirteen patients with nonfunctioning adrenal adenoma (NF), primary aldosteronism (PA), Cushing's syndrome (CS), and mild autonomous cortisol secretion (MACS).
METHODS: Salivary samples for morning and night steroids were collected using standardized protocols. The liquid chromatography-mass spectrometry-based steroid profiling was applied to quantify cortisol, cortisone, tetrahydrocortisone (THE), 20α-dihydrocortisol (20α-DHF), 18-hydroxycortisol (18-OHF), and dehydroepiandrosterone sulfate (DHEA-S).
MAIN OUTCOME MEASURE: The primary outcome was the diagnostic performance of morning and night salivary steroids.
RESULTS: In the PA group, morning and night salivary levels of 18-OHF were higher compared to other groups (all P<.05). Morning and night salivary levels of cortisone, THE, and 20α-DHF were significantly elevated in the CS group compared to other groups (all P<.05). Only night-time salivary levels of cortisone (P=.040) and 20α-DHF(P=.029) were elevated in the MACS group compared to the NF group. Receiver operating characteristic analyses indicated that morning salivary 18-OHF was moderately specific for PA, whereas night salivary 20α-DHF and cortisone provided robust diagnostic accuracy for CS. Combined night salivary steroids exhibited superior diagnostic performance compared to morning salivary steroids in the CS group (AUC, 0.903 vs. 0.754, P = .007).
CONCLUSION: Salivary steroid profiling holds promise as a non-invasive tool for the diagnosis of adrenal diseases.

Keywords:  Cushing’ syndrome; Mild autonomous cortisol secretion; Non-functioning adrenal adenoma; Primary aldosteronism; Salivary; Steroid profiles

DOI:  https://doi.org/10.1210/clinem/dgaf499
J Clin Invest. 2025 Aug 28. pii: e195268. [Epub ahead of print]

Reduced heparan sulfate levels in cerebrospinal fluid reflect brain neuron correction in Sanfilippo B mice.

Steven Q Le, Alexander Sorensen, Soila Sukupolvi, Gianna Jewhurst, Grant L Austin, Balraj Doray, Jonathan D Cooper, Patricia I Dickson.



Keywords:  Biomarkers; Genetics; Lysosomes; Neurological disorders; Neuroscience

DOI:  https://doi.org/10.1172/JCI195268
Horm Behav. 2025 Aug 29. pii: S0018-506X(25)00132-1. [Epub ahead of print]175 105806

Hormonal contraceptive use in relation to basal and reactive testosterone, DHEAS, and cortisol.

Kathleen V Casto, Sally Farah, Ariel Castro, Modupe Akinola, Pranjal H Mehta.

  A burgeoning area of research has begun to uncover a wide range of potential neurological and psychological correlates of hormonal contraceptive (HC) use. Yet there remains a limited understanding of the underlying mechanisms for how HC use alters aspects of neurobiology and related behavioral outcomes. Uncovering these processes has the potential for new discovery in the field of behavioral neuroendocrinology, particularly in the complex interplay between steroid hormone subclasses. Although prior research has often focused on the effects of HC use on progestogen and estrogen disruption, basal and reactive androgens and cortisol may also be significantly impacted by HC use and serve critical functions throughout the brain and body. We discuss important background information on the synthesis and function of three steroid hormones - testosterone, dehydroepiandrosterone-sulfate (DHEAS), and cortisol, review prior research showing how HC use is related to circulating (basal) and reactive levels, and provide sample data on salivary levels from our own research. The combined evidence shows that HC use, specifically of the OC pill, is associated with significantly reduced total, free, and salivary androgens, increased total cortisol in blood but not saliva, and a blunted salivary cortisol response to social stressors. Limited evidence provides initial indication that the specific estrogen and progestin compounds in HC formulas may differentially impact steroid hormone levels. Finally, we discuss the mechanisms by which HCs alter steroid hormone levels, the potential implications of these effects on brain and behavior outcomes, and considerations for future research.

Keywords:  Cortisol; DHEAS; Hormonal contraceptive; IUD; Oral contraceptive pill; Progestin; Testosterone

DOI:  https://doi.org/10.1016/j.yhbeh.2025.105806