Syntara · Small Molecule · Small Molecule
mannitol is a small molecule developed by Syntara. It is approved for therapeutic indications via inhaled.
| Brand Names | Aridol, Osmohale |
| Company | Syntara |
| Drug Class | Small Molecule |
| Route | Inhaled |
| Status | Approved |
mannitol is developed for 1 unique indication across 1 therapeutic area.
| Therapeutic Area | Condition | Phase |
|---|---|---|
| Respiratory, thoracic and mediastinal disorders | Respiratory failure | ✓ Approved |
Barreto George Pereira GP, da Silva Wallace Andrino WA
Carvalho Maria Clara da Cruz MCDC, Mota Ana Carolina Costa Campos ACCC, do Nascimento Daniele de Souza Marinho DSM, de Sousa Ingrid Naihara França INF et al.
Obesity may affect gut health by altering the intestinal barrier function. Excess body fat disrupts plasma levels of fat-soluble vitamins, such as vitamin A, which is crucial for maintaining intestinal permeability. Thus, excess body fat and low retinol concentrations may contribute to intestinal barrier dysfunction in individuals, a condition that remains poorly understood in the context of overweight and obesity. This study aimed to evaluate the associations of overweight and obesity with intestinal barrier permeability, usual dietary intake, and serum retinol concentrations. This cross-sectional study included 89 individuals aged >18 years, with data collected from October 2019 to March 2023. Self-reported disease status, anthropometric measures (weight, height, waist, and hip circumferences), biochemical measures (lipid profile, glycemic status, serum retinol, and α-tocopherol levels), intestinal permeability, and dietary usual intake (using two 24-h recalls and the MSM method) were collected. individuals with overweight or obesity exhibited lower intestinal permeability measured by the Lactulose/Mannitol test (0.035 [0.016-0.064] vs 0.060 [0.028-0.092]; P = 0.036). Usual dietary intake, including vitamin A consumption, did not differ between groups (391.49 [291.49-572.98] μg vs. 368.21 [190.42-557.06] μg; P = 0.545). Despite similar intakes, individuals with overweight or obesity had significantly higher serum retinol concentrations (1.51 vs. 1.00 μmol/L; p = 0.013), suggesting that differences in vitamin A status are more likely driven by metabolic alterations than by dietary intake. BMI correlated positively with anthropometric adiposity markers (waist: ρ = 0.864; hip: ρ = 0.854; WHR: ρ = 0.391; all p < 0.001) and metabolic parameters, including triglycerides (ρ = 0.479; p < 0.001), insulin (ρ = 0.749; p < 0.001), HOMA-IR (ρ = 0.740; p < 0.001), CRP (ρ = 0.500; p < 0.001), and serum retinol (ρ = 0.301; p = 0.004). Inverse correlations were found with HDL-cholesterol (ρ = -0.358; p = 0.001), fiber intake (ρ = -0.328; p = 0.002), and the lactulose/mannitol ratio (ρ = -0.214; p = 0.044). Serum retinol was inversely correlated with the lactulose/mannitol ratio (ρ = -0.373; p < 0.001) and lactulose excretion (ρ = -0.370; p < 0.001), but not with mannitol excretion (ρ = 0.067; p = 0.530). In the adjusted logistic regression, higher retinol levels were significantly associated with overweight/obesity (AOR = 1.781; 95% CI: 1.012-3.134; p = 0.045). Overweight and obese individuals showed lower intestinal permeability and higher serum retinol levels, despite similar dietary intake. Retinol was independently associated with overweight/obesity, suggesting complex interactions between vitamin A status, metabolic alterations, and intestinal barrier function. These changes may warrant further investigation and clinical attention.
Betancourt Sanchez Aldo A, Huynh Alexander A, Blanchard Laurence L, De Groot Arjan A et al.
Two pigmented bacteria strains were isolated from the Mediterranean Sea. Phylogenetic analysis revealed that both strains are affiliated with Winograsdskyella schleiferi Z215. However, in contrast to this reference strain, they can assimilate additional carbon sources such as d-mannose, l-arabinose, d-mannitol, and citrate. Zeaxanthin was identified as the major carotenoid produced by both strains, predominantly in the all-trans configuration. Carotenoid biosynthesis kinetics revealed that pigment production commenced at the early stages of growth, with maximal yields reached between 48 and 56 h (between 1 and 1.3 mg L-1). Specific production yields were 0.7 and 0.9 mg g-1 for the two strains, respectively. Total carotenoid production was influenced by incubation temperature in both strains. Overall, these findings expand the scientific knowledge on carotenoid-producing marine bacteria and highlight the potential of these newly isolated strains as promising candidates for zeaxanthin biotechnological production for a wide range of novel applications ranging from feed additives to treatments for macular degeneration and melanoma.
Chen Jing J, Zhang Ling L
Central retinal artery occlusion (CRAO) is a rare but vision-threatening complication following retinal detachment surgery. We report a man in his late 60s who underwent combined phacoemulsification with intraocular lens implantation and segmental scleral buckling for macula-sparing rhegmatogenous retinal detachment caused by inferotemporal ora dialysis. Shortly after surgery, he developed recurrent ocular pain with marked intraocular pressure (IOP) spikes, anterior chamber shallowing, iris bombe, and secondary angle closure. Approximately 3 h post-operatively, visual acuity deteriorated to no light perception. Fundus examination showed diffuse retinal whitening, a cherry-red spot, and marked retinal arterial attenuation. Fluorescein angiography demonstrated delayed retinal arterial filling, with focal choroidal hypoperfusion, consistent with CRAO with associated focal choroidal hypoperfusion rather than primary ophthalmic artery occlusion. Anterior segment optical coherence tomography showed forward displacement of the intraocular lens-iris diaphragm and angle closure. The patient was treated promptly with repeated anterior chamber paracentesis, topical pilocarpine, topical and systemic IOP-lowering therapy, intravenous mannitol, oxygen therapy, and adjunctive supportive treatment. IOP gradually normalized, and anterior chamber depth recovered. However, visual recovery was limited, with hand motion vision persisting during follow-up. Although the mechanism cannot be proven definitively, the temporal sequence and anterior segment findings suggest that buckle-related anterior segment crowding may have led to forward displacement of the intraocular lens-iris diaphragm, secondary angle closure, and recurrent acute ocular hypertension, thereby contributing to critically reduced ocular perfusion pressure and retinal ischemia. This case highlights the need for urgent reassessment of IOP, anterior chamber configuration, and retinal perfusion when recurrent ocular pain and shallow anterior chamber occur after scleral buckling surgery.
Ye Qiushi Q, Boyenle Ibrahim D ID, Hemesath Holly H, Carillo Kathleen Joyce KJ et al.
Sorcin is a dimeric penta-EF-hand Ca 2+ -binding protein that regulates intracellular Ca 2+ homeostasis through Ca 2+ -dependent conformational activation and target recognition, and it has also been implicated in multidrug resistance in cancer. Although crystal structures have defined the apo inactive and Ca 2+ -bound active states of Sorcin, the transition pathways connecting these states and the conformational ensembles populated under each condition remain poorly understood. Here, we used long-timescale all-atom molecular dynamics simulations on Anton 3, totaling ∼90 μs, to define the Ca 2+ -coupled conformational landscape of dimeric human Sorcin at atomic resolution. Starting from the Ca 2+ -bound structure, we directly observed the transition from the active to the inactive state following Ca 2+ removal, demonstrating that loss of Ca 2+ coordination is sufficient to drive inactivation on the microsecond timescale. Simulations initiated from the Ca 2+ -bound crystal structure with retained ions unexpectedly revealed ultrafast Ca 2+ dissociation and rebinding at all EF-hand sites, indicating weak intrinsic Ca 2+ affinity and highly dynamic ion exchange. In complementary simulations initiated from the apo structure, Sorcin spontaneously sampled active-like conformations even in the absence of stable Ca 2+ binding, supporting a conformational selection mechanism in which Ca 2+ shifts the population toward pre-existing active states rather than inducing the transition de novo. Across all conditions, we also observed pronounced and persistent structural asymmetry between the two protomers, revealing that the Sorcin homodimer is dynamically heterogeneous despite its symmetric crystal structures. Together, these results support a coordination-biased conformational selection model for Sorcin activation, in which weak and rapidly exchanging Ca 2+ binding stabilizes, rather than induces, the active state. This work provides a dynamic framework for understanding Sorcin function as a fast Ca 2+ sensor and offers broader mechanistic insight into activation principles of EF-hand Ca 2+ -binding proteins.
Weich M M, Christl L L, Kiesel M M, Salmen J J et al.
The antibody-drug conjugates (ADCs) sacituzumab govitecan (SG) and datopotamab deruxtecan target trophoblast cell surface antigen 2 (TROP-2) and have shown significant efficacy in HER2-negative metastatic breast cancer (mBC). As TROP-2 may serve as a target across multiple treatment lines, detailed information on TROP-2 expression over time is of great interest. TROP-2 expression was analyzed in breast cancer (BC) samples from patients treated at the University Hospital Würzburg between 2004 and 2025 at clinically indicated biopsy time points (TP), and, in a subset, before and after SG treatment. Expression was assessed immunohistochemically using the H-score (range 0-300). We evaluated 229 samples from 76 patients. Overall, patient-level TROP-2 expression was high (mean H-score 241.3 ± 73.2) and largely stable over time (TP1: 235.7 ± 60.8, n = 76; TP2: 244.6 ± 77.4, n = 72; TP3: 245.3 ± 84.4, n = 39; TP4: 244.9 ± 95.6, n = 8). However, 21 patients exhibited a decline in TROP-2 expression during disease progression, defined as a decrease of ≥ 50 H-score points between two consecutive TPs. Among 13 patients with paired biopsies obtained pre- and post-SG treatment, the mean TROP-2 H-score decreased from 227.0 ± 74.6 before SG to 202.9 ± 99.4 after SG (mean change - 24.1 ± 86.0; median 1.7, range - 170 to 110; Wilcoxon p = 0.542). TROP-2 H-score decreased in 6/13 patients and increased in 7/13 patients. Exploratory PFS analysis showed no statistically significant difference by post-SG TROP-2 change (log-rank p = 0.526). TROP-2 expression was generally high and relatively stable; however, some patients showed declining levels over time.
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