Insulin resistance (IR) is the key driver of type 2 diabetes mellitus, metabolic dysfunction-associated steatotic liver disease, and cardiometabolic disorders. Mesenchymal stem cell-derived exosomes (MSC-Exos) as a potent cell-free alternative can deliver miRNAs, proteins, and mitochondrial regulators to reactivate the IRS1/PI3K/Akt/GLUT4 axis. Beyond restoring insulin signalling, these vesicles can protect β-cells, alleviate endoplasmic reticulum stress, rescue mitochondrial mitophagy and respiration. The genetic engineering strategies including improving the expression of miR-21, miR-3075, or Sirtuin-3, and silencing miR-29b-3p amplify the therapeutic efficacy. However, scalable good manufacturing practice production, long-term safety of modified products, and advanced therapy medicinal product regulation are still needed to overcome. This review will introduce the potential of gene-modified MSC-Exos and miRNAs targeting insulin signalling and mitochondrial rescue, which have shown a shift from symptomatic relief to precision disease-modifying therapy for IR.
Sepsis, a life-threatening condition characterized by systemic inflammation and immune dysregulation, remains a major cause of mortality worldwide. Here, we identify a synthetic sulfonamide intermediate, 1-[5-(2-fluorophenyl)furan-2-yl]-N-(4-methylbenzyl)methanamine (FMM), as a host-directed therapeutic candidate that enhances neutrophil maturation and antimicrobial function via autophagy. In a Pseudomonas aeruginosa-induced sepsis model, FMM administration markedly improved survival and attenuated inflammatory cytokine levels while reducing tissue injury and immune cell apoptosis. Furthermore, FMM promoted bone marrow neutrophil maturation, increased reactive oxygen species generation, and enhanced neutrophil extracellular trap formation. FMM also activated GPCR-mediated Gβγ-PLC signalling, which triggered intracellular calcium and ERK/p38 phosphorylation. Notably, FMM lacked direct bactericidal activity, suggesting its therapeutic effects are mediated by host immune modulation rather than pathogen targeting. Collectively, these findings demonstrate that FMM exerts potent pharmacological effects on neutrophil function and represents a promising lead compound for developing host-directed immunomodulatory therapies for sepsis.
Purmorphamine (PUR) is a trisubstituted purine compound that selectively activates Smoothened receptor, thereby initiating Sonic Hedgehog (Shh) signalling-a pathway critical for embryonic patterning, neuronal specification and tissue regeneration across multiple organ systems. Dysregulation of Shh signalling has been implicated in degenerative diseases yet therapeutic interventions targeting this pathway remain limited. PUR demonstrates broad therapeutic efficacy across diverse preclinical disease models by activating both canonical GLI-mediated transcription and non-canonical Shh pathways, resulting in neuroprotection, reduced neuroinflammation, enhanced blood-brain barrier integrity and tissue regeneration. In contrast to previous assumptions that Shh pathway activation requires endogenous ligand binding, PUR bypasses this requirement through direct Smoothened engagement, offering a pharmacologically tractable approach to pathway modulation. Preclinical studies demonstrate that PUR enhances motor neuron survival in amyotrophic lateral sclerosis models, protects dopaminergic neurons in Parkinson's disease, reverses behavioural abnormalities in autism spectrum disorder, promotes neurovascular repair following stroke, restores myelin integrity in multiple sclerosis models and drives osteogenic differentiation in bone tissue engineering applications. Beyond its established Smoothened agonist activity, recent evidence identifies PUR as a positive allosteric modulator of the secretin receptor, expanding its therapeutic scope to include cardiovascular applications such as hypertension management through enhanced nitric oxide bioavailability.
Graphene oxide (GO) has been recognised to have a strong protein-binding ability attributed to its high surface area and oxygen functional groups (OFGs) but is plagued with dose-dependent cytotoxicity. In contrast, hydroxyapatite (HA) is highly biocompatible but has shown relatively weak protein-protein interactions on the molecular scale. The strategic merging of GO and HA into the GO-HA nanocomposite has the potential to synergistically and precisely facilitate bioactivity and biocompatibility across the implant-tissue interface. Molecular docking, pharmacophore modelling, and molecular dynamics simulations were used to explore the molecular interactions of GO, HA, and GO-HA nanocomposites with ECM proteins, including fibronectin (FN), collagen (COL), laminin (LAM), periostin (POSTN), vitronectin (VN), and osseointegration-related integrin receptors under physiological conditions. The GO-HA nanocomposites exhibited an enhanced number of hydrogen bonds and decreased residue-level fluctuations relative to GO or HA individually, indicating improved interfacial interaction stability at the protein-surface interface. Molecular dynamics simulation results indicated that ECM proteins in the presence of GO-HA showed better conformational stability, which might lead to favourable integrin-mediated adhesion. Preliminary in silico toxicity-related screening of the individual GO and HA model structures suggested differential safety alert patterns, with GO showing more cautionary alerts than HA. These outputs were interpreted qualitatively because the predictive tools used were primarily designed for small molecules rather than nanomaterials. Overall, these in silico results at the molecular scale revealed insights into the surface-biomolecule interactions of GO-HA, which may pertain to early events in osseointegration and can be used to create awareness for downstream in vitro and in vivo validation of dental implant coatings.
This current study aimed to decipher the anti-inflammatory, anti-ferroptosis and pronounced lung-protective activities of Salvianolic acid B (Sal B) by integrating network pharmacology and experimental confirmation across multiple aspects. The optimal target protein and the relevant molecular mechanisms for Sal B in the context of ALI were analysed using network pharmacology. Molecular dynamics simulations and BLI were performed on the core protein ALB-compound Sal B identified through molecular docking. The pharmacological efficacy of Sal B and its underlying mechanisms were further substantiated through both in vitro and in vivo experiments, utilizing the LY294002 inhibitor and si-ALB to confirm the involvement of ALB as a target. Additionally, RNA sequencing of murine lung tissues was conducted to further elucidate the molecular mechanism of Sal B. The results of network pharmacology indicated that a total of 155 potential target genes through which Sal B may exert its protective effects against ALI were identified, with essential pathways including PI3K-AKT, TNF and IL-17 signalling pathways. Molecular docking, MD, and BLI demonstrated stable binding between Sal B and the core target ALB. In vitro and in vivo evidence confirmed that Sal B attenuates LPS-induced ALI by inhibiting ferroptosis via the PI3K/AKT axis, as corroborated by LY294002 and si-ALB intervention. RNA sequencing and network pharmacological analysis synergistically revealed the PI3K/AKT pathway as a potential signalling pathway for Sal B. Sal B ameliorates sepsis-induced ALI via a defined mechanism that involves the activation of the PI3K-AKT pathway, thereby inhibiting ferroptosis both in vivo and in vitro.
Bruton tyrosine kinase inhibitors (BTKis) have been employed in the treatment of mantle cell lymphoma (MCL). However, direct comparisons of ibrutinib, zanubrutinib, and acalabrutinib across treatment-naïve (TN) and relapsed/refractory (R/R) MCL remain limited. This meta-analysis was intended to evaluate their efficacy, addressing critical gaps in clinical decision-making. We systematically searched PubMed, Embase, and Cochrane up to January 2025 for studies (RCT/single-arm) assessing the efficacy of BTKis in MCL patients. Among 70 studies, the pooled CR rate in the TN group was higher than that in the R/R group (76.5% vs. 43.2%). Among TN patients, the CR rate of the regimen incorporating zanubrutinib (95.2% [95% CI 0.893, 1.000]) was significantly higher than that of the regimens containing acalabrutinib or ibrutinib (p = 0.0042). In the R/R group, the BTKi + anti-CD20 monoclonal antibody + small-molecular therapy group presented a better CR rate (68.3% [95% CI 0.546, 0.820]; p < 0.0001). When comparing the monotherapy efficacy of three BTKis in R/R MCL, the results indicated that acalabrutinib exhibited a higher CR rate (43.2% [95% CI 0.339, 0.525]) than zanubrutinib or ibrutinib. In addition, zanubrutinib-based therapy exhibited a lower pooled rate of haematological toxicities compared to the other two BTKi therapies. This work resolved critical uncertainties in BTKi selection for MCL, demonstrating acalabrutinib's and zanubrutinib's first-line potential, leading to a meaningful improvement in response rate and a manageable safety profile. Chemotherapy-free regimen can partially overcome the traditionally unfavourable prognosis associated with R/R MCL. These results provide a roadmap for optimizing MCL therapy. Chemotherapy-free regimens for MCL based on BTKis warrant further validation in RCTs. These findings may advocate for updated guidelines prioritizing zanubrutinib and acalabrutinib in clinical practice.
Sputum culture conversion (SCC) at 2 months is an early indicator of tuberculosis (TB) treatment response, yet the associated immune alterations remain incompletely defined. We performed single-cell RNA sequencing on peripheral blood mononuclear cells from eight TB patients, stratified by 2-month SCC status. Non-responders showed a relative enrichment of non-classical monocytes and higher TB progression risk scores. CellChat analysis inferred altered IL16 and TRAIL communication involving these cells. CD4+ Tregs in non-responders showed higher LGALS9 expression and inferred GALECTIN signalling towards cytotoxic lymphocyte subsets; cell-level LGALS9 co-expression correlated with HAVCR2 and TIGIT in non-responders. Mature NK subclusters showed distinct enrichment profiles. These results describe an observational, transcriptomic and computationally inferred immune network associated with early treatment non-response. They generate candidate biomarkers and hypotheses for prospective protein-level and functional validation.
Glioblastoma progression is driven by stemness acquisition and cellular plasticity, yet the temporal and spatial organization of these processes remains incompletely defined. In this study, single-cell RNA sequencing, pseudotime reconstruction, spatial transcriptomics, and in vitro and in vivo functional assays were integrated to delineate the role of SOX9 during glioblastoma stemness acquisition. SOX9 expression peaked during the early astrocyte-to-malignant transition and declined after malignant states became stabilized. Along pseudotime, SOX9 was inversely associated with the upstream Hippo kinase module and showed phase-dependent coupling with YAP/TAZ-associated transcriptional programmes. Spatial analyses further revealed marked regional heterogeneity, with the strongest SOX9-malignant coupling observed in the perivascular niche. Functionally, SOX9 gain and loss produced reciprocal changes in glioblastoma cell proliferation, migration, invasion, apoptosis, and xenograft growth, while pharmacological modulation of Hippo signalling partially rescued the effects induced by SOX9 loss. Consistent pathway-level changes were also observed in YAP/TAZ expression and p-YAP/YAP and p-MOB1/MOB1 ratios, and xenograft histology showed SOX9-associated morphological and CD68-positive cell changes. These findings identify SOX9 as a temporally restricted regulator of glioblastoma stemness acquisition and support an early priming-late decoupling model of Hippo-YAP/TAZ rewiring, providing a rationale for stage-specific and niche-aware therapeutic targeting in glioblastoma.
Inactivation of the major transcription elongation kinase, cyclin-dependent kinase 12 (CDK12), characterizes a subset of aggressive prostate cancers but it is not known how cells adapt and even benefit from this event. We show that mutations in the CDK12 gene are associated with decreased DNA methylation in patient tumours and dual inhibition of the major transcription elongation kinases, CDK12 and CDK13 decreases DNA methylation in vitro. This decrease in DNA methylation occurs particularly in the target genes of MYC (MYC Proto-Oncogene). Previously, it was established that CDK12 inhibition impairs homologous recombination, while increase in MYC activity causes DNA replication stress. We therefore hypothesized that CDK12/13 inhibition renders cells dependent on high DNA-PK activity, which is required for non-homologous end joining. Indeed, we show that genetic and pharmacological targeting of DNA-PK is toxic to cancer cells in combination with CDK12/13 inhibition. In brief, here we show that decrease in CDK12/13 activity depletes DNA methylation from MYC target genes and propose that CDK12 inactivation may serve as a biomarker of sensitivity to DNA-PK inhibitors.
Vascular calcification is a pathological process involving vascular smooth muscle cells (VSMCs) phenotypic switching into osteoblast-like cells within a calcium phosphate-deposited environment. This transformation is a critical risk factor for cardiovascular morbidity and mortality in patients with hyperphosphatemia due to chronic kidney disease. Corylin, a major compound derived from the Chinese medicine herb Psoralea corylifolia, is beneficial for the cardiovascular system. However, its role in modulating VSMC phenotypic switching and calcification remains to be elucidated. A vascular calcification rat model induced by vitamin D3 plus nicotine (VDN) was established to evaluate the therapeutic effects of corylin. The protective effects of corylin were evaluated in high phosphate-induced vessels and VSMCs using cytotoxicity assay, Alizarin red S staining, alkaline phosphatase staining, immunofluorescence, Western blot analysis, and qPCR. The interaction between Jun dimerisation protein 2 (JDP2) and Nrf2 was analysed using a ChIP-qPCR assay. Corylin treatment ameliorated arteriosclerotic lesions and oxidative stress in rats treated with VDN. We also observed that the cytoprotective effects of corylin prevented VSMC apoptosis and deposition of calcium phosphates. Additionally, corylin decreased calcium overload by inhibiting calcineurin and maintaining mitochondrial homeostasis. We identified a robust co-induction of JDP2 and Nrf2 in corylin-treated VSMCs, which contributed to reducing phenotypic switching and abrogating oxidative stress. Furthermore, Nrf2 knockdown by an inhibitor abolished JDP2 activation and the protective effects of corylin. Our study reveals that corylin exerts anti-arteriosclerotic and vasculoprotective effects targeting JDP2-Nrf2 activation, making it a potential treatment for vascular calcification.
Toxoplasma gondii infection poses potential risks to stem cell-based therapeutic applications; however, the effects of parasite-derived soluble factors on mesenchymal stem cells remain unclear. Here, we investigated the impact of T. gondii-derived soluble factors (Tg-SFs) on human umbilical cord-derived mesenchymal stem cells (hUC-MSCs). hUC-MSCs were exposed to Tg-SFs generated in a Transwell co-culture system, and cellular phenotypes and p53 signalling were analysed using integrated functional and molecular approaches. Tg-SFs induced upper-chamber multiplicity of infection (MOI)-dependent cytotoxicity in hUC-MSCs, accompanied by cytoskeletal remodelling and nuclear condensation. Tg-SFs exposure caused marked G2/M phase accumulation, which was accompanied by reduced expression of Cyclin A2, Cyclin B1, and Cyclin E2 and increased p21 expression. In addition, Tg-SFs exposure reduced phosphorylation of CDK1 at Thr161. Tg-SFs-exposed hUC-MSCs underwent significant apoptosis, as evidenced by PARP and Caspase-3 cleavage. Mechanistically, Tg-SFs promoted accumulation of total p53 protein and selective phosphorylation of p53 at Ser15 and Ser392, and modulated Bcl-2 family proteins by upregulating Bax, BID, Bak, Bad, and Puma while downregulating Bcl-xL and Mcl-1. Pharmacological inhibition of p53 with PFT-α and siRNA-mediated p53 knockdown partially reversed these effects, indicating that p53 signalling contributes substantially, but not exclusively, to Tg-SFs-induced mitochondrial apoptosis. These findings indicate that T. gondii-derived soluble factors impair hUC-MSC viability through G2/M phase accumulation and p53-associated mitochondrial apoptosis, highlighting a potential safety consideration for MSC-based applications under parasite-associated conditions.
Myotonic dystrophy type 1 (DM1) is a progressive muscular disorder caused by the expansion of CTG repeats in the 3' UTR of the DMPK gene. Although the pathogenic mechanisms remain unclear, recent evidence suggests that activation of innate immune responses may contribute to disease progression. In this study, we examined the ultrastructure and proteomic data of myoblasts from young adult DM1 patients carrying approximately 800 and 1300 CTG repeats in order to investigate a link between cellular stress and immune activation. We observed activation of the type I interferon (IFN-I) pathway associated with rough endoplasmic reticulum stress (sRER). The sRER response is likely triggered by the accumulation of toxic RNA species generated from the expanded DMPK allele. Our data suggest that this inappropriate activation of the IFN-I pathway contributes to muscle pathology, not by blocking differentiation directly, but through chronic stress signalling. These findings support a model in which innate immune dysregulation plays a central role in DM1 muscle degeneration and highlight the IFN1 pathway as a potential therapeutic target for restoring normal muscle function.
tsRNAs are a kind of small non-coding single-stranded RNA, which play an important role in many kinds of tumours. Previous studies have identified that tRF-31-U5YKFN8DYDZDD can be used as a novel tumour biomarker for the diagnosis and prognosis of gastric cancer (GC). In this study, we further explored the regulatory effect of tRF-31-U5YKFN8DYDZDD on tumour biological function in GC cells and related regulatory mechanisms. Inhibition of tRF-31-U5YKFN8DYDZDD can inhibit the proliferation, invasion, migration and angiogenesis of GC cells, while overexpression of tRF-31-U5YKFN8DYDZDD has the opposite effect. BMPER was shown to be a direct target of tRF-31-U5YKFN8DYDZDD in GC. Furthermore, the cytological effects of stable overexpression of BMPER were similar to the inhibition of tRF-31-U5YKFN8DYDZDD. And the attenuation of BMPER expression rescued the tRF-mediated promotion of GC cells. WB showed that up-regulation of tRF-31-U5YKFN8DYDZDD could increase the phosphorylation level of ERK and Smad1/5, and promote the expression of epithelial mesenchymal transition (EMT) and matrix metalloproteinases. Animal experiments in vivo show that down-regulation of tRF-31-U5YKFN8DYDZDD can effectively inhibit tumour growth. These data suggest that tRF-31-U5YKFN8DYDZDD is a new tumour-promoting factor and may be a potential new therapeutic target for GC.
To investigate the involvement of metalloproteinases (MMPs) in the context of endurance training and their interactions with renin-angiotensin signalling (RAS) in stress-induced pathophysiological responses. Trained rats were submitted to 8-weeks of endurance treadmill training with chronic mild stress (CMS), TS rats, and without CMS (T). Non-trained rats (NTS and NT groups) were submitted to identical procedures except for training. NTS and TS groups were submitted to a CMS protocol for 3 weeks. Elevated corticosterone levels indicate an initial triggering factor that mediates the downstream intracellular signalling networks related to the MMPs and RAS activation after CMS. Endurance training confers cardioprotection against the stress response by lowering the Ang 3-7 levels, whereas increased activity of MMPs was observed in TS rats. Chronic stress disrupts the cardiac function, MMPs, and RAS activation by increasing the cardiac activity of the MMP-2 activity and Ang 1-9 levels with concomitant reduction of cardiac and blood levels of Ang 1-7. Stress also reduced circulating levels of Ang 1-9 and Ang 1-5, Ang 1-7 metabolites, along with increased Ang III (2-8). Aerobic endurance training is a potential exercise-based strategy that counteracts the stress-related disturbances in the MMPs and RAS signalling pathways.
Extracellular vesicles (EVs/EV) are key mediators of intercellular communication and influence proliferation, migration, and metabolic reprogramming. In breast cancer, EVs released by malignant cells carry bioactive molecules capable of altering the behaviour of surrounding cells. However, it remains uncertain whether these vesicles can directly induce a more aggressive phenotype in benign mammary cells. Melatonin, known for its oncostatic properties, regulates proliferation, metabolism, and signalling pathways associated with tumour progression and may modulate EV-mediated intercellular communication. This study evaluated whether EVs derived from four breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-453 and HCC70), treated or not with melatonin, can modify the phenotype of benign MCF10A cells. EVs were isolated from conditioned media and co-cultured with benign cells. Assays of proliferation, viability, colony formation, migration, lactate production and immunofluorescence were performed to assess EV-mediated effects. EVs derived from malignant cells promoted a more aggressive phenotype in benign cells, as evidenced by increased proliferation, migration, and phenotypic remodelling. In contrast, EVs derived from melatonin-treated malignant cells were associated with reduced lactate production and attenuation of pro-tumoural features. Overall, these findings demonstrate that tumour-derived EVs can induce aggressive traits in benign mammary cells and suggest that melatonin exposure in donor cells modulates EV-mediated effects, attenuating their pro-tumoural influence.
RAS mutations occur in patients with several types of vascular anomalies, but effective treatments remain limited. To address this need, we evaluated the RAS (ON) multi-selective inhibitor RMC-7977 in human endothelial cells (ECs) expressing the NRASQ61R mutation found in kaposiform lymphangiomatosis (KLA). RMC-7977 was evaluated using in vitro and in vivo models. Doxycycline-inducible NRASWT and NRASQ61R human ECs were treated with RMC-7977 (3.12-100 nM) or vehicle. We assessed signalling pathways, proliferation, migration, morphology, and angiopoietin-2 (ANG-2) production. NRASQ61R ECs in a 3D angiogenesis assay were also treated with RMC-7977. For in vivo studies, NRASQ61R ECs were injected into flanks of nude mice on a doxycycline diet to generate xenografts. Mice received oral RMC-7977 or vehicle, and xenografts were collected after 11 days. RMC-7977 inhibited NRASQ61R-induced ERK phosphorylation and reduced proliferation, migration, spindle-like morphology, and ANG-2 production in a dose-dependent manner. RMC-7977 reduced vascular area in the angiogenesis assay. In vivo, RMC-7977 reduced xenograft weight, vascular area, and p-ERK staining. Overall, RMC-7977 suppressed NRASQ61R-mediated signalling, aberrant EC behaviour, and ANG-2 production in vitro and reduced vascular overgrowth in angiogenesis assays and mouse xenografts. Therefore, RMC-7977 may be a promising therapeutic candidate for RAS-driven vascular anomalies, including KLA.
Post-operative cognitive dysfunction (POCD) is a cognitive disorder characterized by a decline in cognitive function following surgical procedures, with mitophagy identified as a significant underlying mechanism. Protein kinase C delta (PRKCD), localized within the mitochondria, is implicated in the regulation of PINK1/PRKN mitophagy pathway; however, the potential regulatory role of PRKCD in POCD through this pathway remains to be elucidated. Neurons and rats were exposed to sevoflurane (SEV) to illuminate the function and mechanism of PRKCD in POCD. Various methodologies were employed, including immunofluorescence, quantitative real-time PCR, CCK-8 assays, mitochondrial membrane potential (MMP) assessments, MitoSOX generation detection, Seahorse metabolic flux analysis, co-immunoprecipitation, western blotting and behavioural experiments like Morris water maze, novel object recognition and fear conditioning, along with haematoxylin and eosin and immunohistochemical staining. PRKCD was expressed in neurons and that SEV administration led to an upregulation of PRKCD expression. Furthermore, interference with PRKCD was found to restore cell viability in SEV-treated neurons. Additionally, inhibition of PRKCD resulted in the recovery of LC3 expression and the normalization of p62 levels in neurons subjected to SEV treatment. Suppressing PRKCD restored MMP and OCR, reduced MitoSOX in SEV-affected neurons and interacted with PRKN and PINK1, decreasing their expression. Overexpressing PRKN mitigated PRKCD inhibition's impact on mitochondrial damage. In vivo, SEV increased PRKCD, PINK1 and PRKN levels, but PRKCD knockdown improved behavioural and pathological outcomes, reversing changes in LC3-II, PINK1, PRKN and p62 expression. PRKCD enhanced SEV-induced POCD in aged rats via the regulation of PINK1/PRKN mitophagy pathway.
Radiation-induced intestinal injury (RIII) is among the most common complications of radiotherapy in patients with abdominaltumours. At present, there are no effective methods for reducing the occurrence or severity of RIII. Berberine (BBR) is a quaternary ammonium alkaloid extracted from Coptis chinensis that has antioxidant, anti-inflammatory, and protective effects on the intestine. A RIII model was established using 10 Gy of X-ray total abdominal irradiation (TAI). The effects of BBR on mice exposed to 10 Gy of X-ray TAI were determined by analysing pathological sections of the mouse intestine. TUNEL staining was used to detect apoptosis of intestinal epithelial cells in mice. Immunohistochemistry was applied to detect the expression of proliferation indicators PCNA and Ki-67, and immunofluorescence staining was used to quantify BrdU-positive proliferative cells. BBR stimulates crypt formation ex vivo after irradiation and upregulates the expression of FXR. The expression of goblet cell and intestinal stem cell markers was quantified by qRT-PCR. The expression of farnesoid X receptor (FXR) in RIII was detected via qRT-PCR and Western blot. Additionally, a Western blot was performed to detect the protein levels of NF-κB, p-p38, total p38, and β-catenin, and qRT-PCR was used to measure the mRNA expression levels of pro-inflammatory factors TNF-α, IL-1β, and IL-6. BBR alleviated RIII, mainly manifested as body weight loss, longer colons, greater numbers of villi, and greater numbers of crypts. BBR also maintained the regeneration ability and promoted the proliferation of crypt cells, reduced the apoptosis rate, and alleviated intestinal injury. Importantly, BBR rescued radiation-induced dysregulation of these key signalling proteins and pro-inflammatory factors. BBR failed to promote the repair of RIII when FXR was inhibited. BBR treatment increased the expression of FXR in crypts and was at least protective against radiation-induced intestinal damage in mice through the modulation of FXR. BBR may be a potential drug for the treatment of radiation-induced intestinal damage.
