CORR Insights®: Is a Resorbable Citrate-based Bioceramic Device Associated With Osseous Integration? An Early Retrospective MRI Analysis.
DeCoster Thomas A TA
Sanofi S.A · Small Molecule · Small Molecule
clomiphene citrate is a small molecule developed by Sanofi S.A. It is approved for therapeutic indications via oral (po).
| Brand Names | Omifin, Clomid |
| Company | Sanofi S.A |
| Drug Class | Small Molecule |
| Route | Oral (PO) |
| Status | Approved |
clomiphene citrate is developed for 1 unique indication across 1 therapeutic area.
| Therapeutic Area | Condition | Phase |
|---|---|---|
| Reproductive system and breast disorders | Infertility female | ✓ Approved |
DeCoster Thomas A TA
Sauer David B DB, Song Jinmei J, Marden Jennifer J JJ, Wang Bing B et al.
The human sodium-citrate cotransporter NaCT imports various tri- and dicarboxylates into the cell as TCA cycle intermediates. This substrate uptake process is driven by an inward sodium gradient. The protein is a member of the Divalent Anion-Sodium Symporter (DASS) family. Whereas extensive biochemical and structural studies have been carried out for NaCT, how the substrate binding and translocation is coupled to the sodium gradient remains unclear. Here using single particle cryo-electron microscopy, we determined the structures of the human NaCT protein in three states: sodium-free, in the presence of sodium, and sodium- and substrate-bound. These structures suggest a simultaneous binding mechanism for sodium-substrate coupling, distinct from the sequential binding, conformational selection mechanism previously observed for the bacterial DASS protein VcINDY.
Bhaskar Siddhesh Sanjay SS, Zine Sandip Prabhakar SP, Bagul Vijay A VA, Tiwari Anand R AR et al.
Analytical Quality-by-Design principles were used to develop and validate a reverse-phase high-performance liquid chromatography method for the simultaneous quantification of butamirate citrate and chlorpheniramine maleate in pharmaceutical formulations. Box- Behnken Design systematically optimized three critical variables mobile phase pH, flow rate, and column temperature with response surface plots confirming robust chromatographic performance. Using an isocratic mobile phase of ethanol: water (40:60 v/v) containing 0.33% triethylamine and adjusted to pH 6.0 using 1% orthophosphoric acid, separation was accomplished on a Waters Spherisorb cyano column (250 mm × 4.6 mm, 5 μm) at 1.2 mL/min with photodiode array detection at 225 nm. Validation per ICH Q2(R2) demonstrated excellent linearity (r²=0.999) across 112-337 μg/mL and 10-30 μg/mL for both analytes, with percentage recoveries of 99% and 98%, respectively. Environmental sustainability was confirmed through Analytical Eco-scale (score: 80), Analytical Greenness metric (0.69), and Complex Modified Green Analytical Procedure Index (83). Analytical performance was evaluated using the Red Analytical Performance Index (70) and Multi-Color Assessment Tool (72.6%), collectively reflecting strong scope, sensitivity, accuracy, and precision. Reliable quantification of both compounds in pharmaceutical dosage forms is offered by a validated, environmentally friendly approach, supporting routine quality control and research applications.
Shahid Mehak M, Ashfaq Isbah I, Haider Burhan B, Tayyeb Asima A
Cancer metabolism especially lipid metabolic reprogramming is considered one of the most important metabolic processes involved in hepatocellular carcinoma (HCC). Solute carrier family 25 member A1 (SLC25A1) is a citrate transporter present in mitochondrial membrane and emerged to play role in lipid metabolic reprogramming. This study aimed to elucidate the mechanistic role of SLC25A1 in lipid metabolic reprogramming and its therapeutic potential in HCC. In the current study, enhanced expression of SLC25A1 gene was observed in toxicant induced mouse model of HCC suggesting a correlation with initiation and development of HCC. However, the precise mechanistic involvement of SLC25A1 in HCC is unclear underscoring the need of an in depth study. Clinical relevance of SLC25A1 in HCC was primarily evaluated using The Cancer Genome Atlas database. The in silico results not only demonstrated a strong correlation between the expression of SLC25A1 and HCC but also associated it with poor survival. In depth gain of function analysis using mammalian expression vector, SLC25A1-PCMV3 in human cell lines exhibited enhanced cellular growth, invasion, and migration potentials of cells expressing SLC25A1. Notably, the overexpression of SLC25A1 was associated with increased de novo lipogenesis, consistent with metabolic reprogramming favoring cytosolic citrate utilizationas evident by upregulation of FASN, ACACA, ACLY, SCD1 and downregulation of IDH2 and OGDH. Virtual screening and molecular docking studies presented rutin, a natural flavonoid, as a potential inhibitor of SLC25A1. In vitro inhibition of SLC25A1 by treatment with rutin significantly suppressed SLC25A1 expression leading to reduced lipogenesis. Collectively, these findings propose SLC25A1 is associated with metabolic reprogramming in HCC and contribute to tumor progression.by promoting lipogenesis. Thus offering a promising therapeutic target for early intervention and treatment.
Ou Qing Q, He Dan D, Yan Wenjuan W, Shi Xiuying X et al.
The optimal anticoagulation strategy for continuous renal replacement therapy (CRRT) remains controversial. Real-world comparisons of contemporary agents-regional citrate anticoagulation (RCA), nafamostat mesylate (NM), and unfractionated heparin (UH)-are limited. In this single-center retrospective cohort study, we analyzed 420 CRRT sessions (from 197 unique patients) conducted in four intensive care unit (ICU) wards at an academic medical center in China between September 2025 and November 2025. The primary efficacy outcome was filter lifespan, with Restricted Mean Survival Time (RMST) analysis adopted as the primary method (due to violation of the proportional hazards assumption). Propensity score matching (PSM) and mixed-effects Cox models were used as sensitivity analyses, adjusting for patient, treatment, ward, and machine factors. Multiplicity adjustment (Holm-Bonferroni) was applied for pairwise comparisons. Among 420 sessions, RCA was the most frequently used approach (59.0%), followed by NM (21.2%), UH (12.6%), and no anticoagulation (4.0%). Median filter lifespan was longest with RCA (65.5 h, IQR 48.0-72.0) compared to NM (32.0 h, IQR 15.5-52.5), UH (40.0 h, IQR 26.0-72.0), and no anticoagulation (12.5 h, IQR 6.0-19.5; P < 0.001). RMST analysis confirmed that RCA was associated with significantly longer mean filter survival time compared to NM (difference 18.2 h, 95% CI 10.5-25.9; adjusted P < 0.001) and UH (difference 14.6 h, 95% CI 5.8-23.4; adjusted P = 0.046). The NM vs. UH comparison showed no significant difference (difference - 3.6 h, 95% CI -12.1 to 4.9; adjusted P = 0.52). After PSM, results remained consistent. Major bleeding events were rare (n = 9, 2.1%), but the small number of events precludes meaningful between-group safety comparison. However, 20.9% of RCA sessions failed to achieve the protocol-specified post-filter ionized calcium target, reflecting a metabolic calcium monitoring challenge unique to citrate anticoagulation. Twenty-eight-day mortality (patient-level analysis, n = 197) did not differ significantly across groups after adjustment (overall 36.5%, 72/197). In this retrospective data analysis of real-world practice, RCA provided superior filter lifespan compared to NM and UH for CRRT, while NM showed intermediate efficacy. Although major bleeding events were uncommon, the small number of events precludes definitive safety conclusions. Vigilant monitoring remains necessary regardless of the agent employed. The choice of anticoagulation should balance filter efficacy, bleeding risk, metabolic monitoring capabilities, and institutional resources.
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.
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