estrogens is a therapeutic agent developed by Teva Pharmaceutical Industries Ltd.. It is approved for therapeutic indications via intravaginal or oral (po).
| Brand Names | Cenestin, Bijuva, Barr |
| Company | Teva Pharmaceutical Industries Ltd. |
| Molecular Target | ESR1 |
| Route | Intravaginal, Oral (PO) |
| Status | Approved |
estrogens acts on 1 molecular target:
| ESR1 | estrogen receptor 1 (ER, ESR) |
estrogens is developed for 3 unique indications across 2 therapeutic areas.
| Therapeutic Area | Condition | Phase |
|---|---|---|
| Reproductive system and breast disorders | Atrophic vulvovaginitis | ✓ Approved |
| Surgical and medical procedures | Hormone replacement therapy | ✓ Approved |
| Reproductive system and breast disorders | Menopausal symptoms | ✓ Approved |
Kang Jing J, Shi Yan Y, Liu Chang C, Shen Lufan L et al.
Wang Xia X, Hu Wei-Ping WP, Wu Yi-Xing YX, Hua Jian-Lan JL et al.
Epstein-Barr virus (EBV) is frequently detected in critically ill patients, but the clinical meaning of EBV reported by blood metagenomic next-generation sequencing (mNGS) in ICU patients with pneumonia remains unclear. This retrospective secondary analysis used data from a prospective multicenter cohort of patients with suspected sepsis. Data included demographics, clinical variables, radiological findings, blood culture and mNGS results, cytokine levels, and 30-day mortality. A total of 184 ICU patients with pneumonia were included and classified as EBV-positive (n=34) or EBV-negative (n=150) according to blood mNGS. EBV-positive patients had lower serum albumin and systolic blood pressure, higher qSOFA score distribution, more frequent sepsis at enrollment, higher C-reactive protein and procalcitonin levels, higher PaCO2, and lower serum calcium. Pneumocystis jirovecii was numerically more frequent in EBV-positive patients but was not independently associated with EBV positivity after adjustment. In exploratory cytokine analysis, EBV-positive patients showed higher TRAIL levels and more frequent IL-17 detection. In an exploratory multivariable model, lower serum albumin and sepsis at enrollment remained associated with EBV positivity. 30-day mortality did not differ significantly between groups. In ICU patients with pneumonia, blood mNGS-detected EBV was associated with markers of disease severity and inflammatory burden. However, these associations do not establish clinically significant EBV reactivation, and no statistically significant difference in 30-day mortality was observed between groups.
Krishnan Selvi S, Periyasamy Bhuvana K BK, Anand Appakkudal R AR
Fluorescent detection is indispensable for microbial detection due to its unparalleled sensitivity and the ability to identify minute quantities of microorganisms. Luorescent dyes emit light upon interaction with specific biomolecules, enabling rapid visualization of microorganisms in complex samples. However, photobleaching, sensitivity to environmental conditions, and non-specific binding associated with conventional fluorescent dyes can limit their performance. Addressing these limitations is important for developing robust and reliable fluorescence-based microbial visualization systems. Conjugated polymer nanoparticles (CPNs) have emerged as promising fluorescent materials because of their enhanced photostability, brightness, and tunable optical properties, which may overcome some limitations of conventional fluorescent dyes. This study explores the application of MEH-PPV CPNs as fluorescent probes for the visualization of microorganisms. The experimental work involved the preparation and characterization of CPNs, optimization of the fluorescent probe concentration, and evaluation of their fluorescence-associated labeling of representative Gram-positive bacteria, Gram-negative bacteria, and yeast. In addition, the applicability of the CPNs for microbial visualization was evaluated using selected clinical samples, where fluorescence associated with microbial cells was observed with relatively low background interference. The findings demonstrate that MEH-PPV CPNs can facilitate rapid fluorescence-based visualization of diverse microbial cells and highlight their potential as an alternative fluorescent material for microbial imaging and staining applications.
Niu Yunfeng Y, Sun Jing J, Han Yusen Y, Guo Ruoyi R et al.
Neuromyelitis optica spectrum disorder (NMOSD) is an AQP4-IgG-mediated astrocytopathy characterized by blood-brain barrier (BBB) injury and myeloid inflammation. We investigated whether interferon-stimulated gene 15 (ISG15) contributes to myeloid activation through RIG-I-like receptor (RLR) signaling. Single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) from patients with NMOSD was combined with validation in monocytes, serum, and cerebrospinal fluid. THP-1-derived macrophages and HMC3/BV2 microglia underwent LPS and/or IFN-β stimulation and ISG15 knockdown or overexpression. To assess macrophage-derived ISG15 effects on microglial polarization, ISG15-manipulated macrophages were non-contact cocultured with microglia in Transwell inserts, and microglial M1/M2 markers were measured. Western blotting quantified free and conjugated ISG15. ISG15-RIG-I association were examined by co-IP. An AQP4-IgG/human complement passive-transfer mouse model provided in vivo validation. NMOSD PBMCs showed monocyte expansion and an ISG15-high interferon/RLR signature, with increased ISG15 in CD14+ monocytes, serum, and cerebrospinal fluid. In macrophages, LPS plus IFN-β increased inflammatory cytokines, migration, and both free/conjugated ISG15. ISG15 overexpression or knockdown bidirectionally altered macrophage and microglial phenotypes; the Transwell coculture confirmed that macrophage ISG15 status directly modulated microglial M1/M2 polarization. ISG15 modulated RIG-I/MDA5/LGP2 expression, with RIG-I overexpression partially rescuing the RLR program after knockdown. Co-IP confirmed physical association between ISG15 and RIG-I. In vivo, BBB disruption coincided with ISG15-high infiltrating and resident myeloid cells and RLR upregulation. Elevated ISG15 following BBB injury reinforces RIG-I/MDA5/LGP2 signaling and drives macrophage-microglia inflammatory crosstalk in NMOSD, establishing the ISG15-RLR axis as a key amplification pathway that bridges peripheral and central myeloid responses.
Henjarappa Krushnamurthy Pattanayakanahalli KP, Ganguly Mahima M, Mukherjee Aritra A, Bhattoo Pooja P et al.
Pyridoxal 5'-phosphate (PLP)-dependent aminotransferases play a central role in nucleoside antibiotic biosynthesis, where they catalyze the conversion of ribose-derived aldehyde intermediates into aminonucleosides by introducing critical amino functional groups. Despite their widespread occurrence in the biosynthetic pathways of several therapeutically important nucleoside antibiotics, the detailed biochemical and mechanistic characterization of these enzymes remains elusive. In this study, we present a comprehensive in vitro reconstitution, structural modeling, and molecular dynamics (MD) simulation-based biochemical and mechanistic investigation of a key aminotransferase, PumG from Streptomyces rimosus (SrPumG), which plays a critical role in the biosynthesis of the potent bacterial RNA polymerase inhibitor, Pseudouridimycin (PUM). Our size-exclusion chromatography and native PAGE analysis, in conjunction with spectroscopic and modeling studies, showed that SrPumG is a stable homodimer that uses a highly conjugated form of the PLP cofactor, along with suitable amino donors, such as L-Arg, to convert pseudouridine aldehyde (PUA) to amino pseudouridine (APU). The structure-based three-dimensional modeling and MD simulation of SrPumG, coupled with site-directed mutagenesis, further confirmed that, in addition to the catalytic residue Lys289, several active-site residues from both protomers facilitate the binding and stabilization of the PLP/PMP cofactor and the PUA substrate via electrostatic/hydrogen-bonding interactions and aromatic stacking. In addition, our studies uncovered key residues that stabilize the dimer interface via hydrophobic and π-π interactions. One notable finding from our study is that SrPumG does not discriminate between C- and N-nucleoside substrates and exhibits a broader substrate scope, which further confirms the gatekeeper role of the preceding oxidoreductase enzyme, PumI, in this pathway. Together, these findings reveal that a distinct highly conjugated form of PLP and an intricate dimer interface architecture, which is essential for substrate/cofactor binding and protein stability, govern SrPumG catalysis. This work provides new insights into aminotransferases in nucleoside biosynthesis and establishes a foundation for engineering the PUM pathway to design new antibacterial derivatives.
Yang Zinan Z, Bai Yang Y, Jia Lihui L, Zhang Ying Y et al.
Oncogenic viral pathogens, such as human papillomavirus (HPV), Epstein-Barr virus (EBV), hepatitis B and C viruses (HBV, HCV), and Kaposi's sarcoma-associated herpesvirus (KSHV), are involved in a significant proportion of human cancers worldwide. While genetic and epigenetic mechanisms underlying viral oncogenesis have been thoroughly investigated, emerging evidence underscores a critical role for epitranscriptomic regulation in virus-host interactions and their clinical consequences. RNA modifications such as N6-methyladenosine (m6A), 5-methylcytosine (m5C), and pseudouridine (Ψ) dynamically modulate RNA stability, translation, and immune recognition, thereby regulating viral replication and persistence. The present review describes current knowledge on the epitranscriptomic landscape of oncogenic viral pathogens and its functional implications. This review discusses how viral and host transcripts are selectively modified by cellular writers, erasers, and readers, shaping key stages of the viral life cycle, including replication, latency, and reactivation. Particular emphasis is placed on the role of RNA modifications in maintaining chronic infection and promoting tumourigenesis through the regulation of oncogenic pathways, cell proliferation, and apoptosis. Additionally, the present review examines how epitranscriptomic marks contribute to immune evasion by altering innate immune sensing and interferon responses. Finally, it explores the therapeutic potential of targeting epitranscriptomic machinery, highlighting recent advances in small-molecule inhibitors and the challenges associated with specificity and off-target effects. A deeper understanding of epitranscriptomic regulation in oncogenic viruses may reveal novel biomarkers and therapeutic strategies for virus-linked malignancies.
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