New bitongling regulates gut microbiota to predict angiogenesis in rheumatoid arthritis via the gut-joint axis: a deep neural network approach DOI Creative Commons

Yin Guan,

Xiaoqian Zhao, Yun Lü

et al.

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 3, 2025

Background Rheumatoid arthritis (RA) is a persistent autoimmune disorder marked by inflammation and joint damage. Although current treatments, such as disease-modifying antirheumatic drugs (DMARDs), help control symptoms, they frequently cause substantial side effects, highlighting the urgent need for safer more effective alternatives. Recent research indicates that gut microbiota might be pivotal in RA development through “gut-joint axis,” presenting novel therapeutic possibilities. Purpose This study seeks to explore potential of traditional Chinese medicine (TCM) compound new bitongling (NBTL) RA, with an emphasis on its capacity regulate suppress angiogenesis via vascular endothelial growth factor (VEGF) signaling pathway. Methods We utilized collagen-induced (CIA) rat model assess impact NBTL. The employed 16S ribosomal DNA (16S rDNA) sequencing analyze composition, machine learning techniques identify characteristic microbial taxa, transcriptomic analysis (GSVA) VEGF findings were further validated deep neural network models vivo / vitro experiments, including western blot, immunofluorescence, miRNA analysis. Results NBTL treatment markedly diminished rats, evidenced reduced expression TNF-α, IL-17, IL-6, ASC synovial tissues. Histopathological confirmed alleviation Five f_Mycoplasmataceae , s_Metamycoplasma_sualvi g_Prevotellaceae_Ga6A1_group identified associated NBTL’s modulation Gene set variation revealed significant downregulation pathway following treatment. Subsequent experiments inhibited receptors, VEGFR1 VEGFR2, along HIF-1α (hypoxia-inducible 1-alpha), thereby reducing angiogenesis. Additionally, upregulated miR-20a-5p miR-223-3p, contributing anti-angiogenic effects. Conclusion exhibits modulating inhibiting These support use promising candidate treatment, emphasizing mechanisms clinical application.

Language: Английский

Precise Photodynamic Therapy by Midkine Nanobody-Engineered Nanoparticles Remodels the Microenvironment of Pancreatic Ductal Adenocarcinoma and Potentiates the Immunotherapy DOI
Chengming Qu, Haitao Yuan, Ming Tian

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(5), P. 4019 - 4037

Published: Jan. 22, 2024

Pancreatic ductal adenocarcinoma (PDAC) is notorious for its resistance against chemotherapy and immunotherapy due to dense desmoplastic immunosuppressive tumor microenvironment (TME). Traditional photodynamic therapy (PDT) was also less effective PDAC owing poor selectivity, insufficient penetration, accumulation of photosensitizers in sites. Here, we designed a light-responsive novel nanoplatform targeting the TME through tumor-specific midkine nanobodies (Nbs), which could efficiently deliver semiconducting polymeric nanoparticles (NPs) locally produce abundant reactive oxygen species (ROS) precise photoimmunotherapy. The synthesized nanocomposite can not only achieve multimodal imaging tumors (fluorescence photoacoustic imaging) but lead apoptosis immunogenic cell death cells via ROS under light excitation, ultimately preventing progression remodeling with increased infiltration T lymphocytes. Combined PD-1 checkpoint blockade, targeted PDT platform showed best antitumor performance markedly extended mice survival. Conclusively, this work integrating Nbs NPs provides strategy target formidable suppression activate immunity, creating possibilities boosting efficacy combination local PDT.

Language: Английский

Citations

24
Physiological premature aging of ovarian blood vessels leads to decline in fertility in middle-aged mice DOI Creative Commons

Lu Mu,

Ge Wang,

Xuebing Yang

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Ovarian function declines significantly as females enter middle-age, but the mechanisms underlying this decline remain unclear. Here, we utilize whole-organ imaging to observe a notable decrease in ovarian blood vessel (oBV) density and angiogenesis intensity of middle-aged mice. This leads diminished supply ovaries, resulting inadequate development maturation follicles. Utilizing genetic-modified mouse models, demonstrate that granulosa cell secreted VEGFA governs angiogenesis, physiological oBV is not attributed insufficiency. Instead, through single-cell sequencing, identify aging vascular endothelium primary factor contributing decline. Consequently, administration salidroside, natural compound functional reverse promote enhances improve fertility older females. Our findings highlight enhancing promising strategy boost study identifies key driver loss female mice demonstrates restoring with Salidroside might be approach aged

Language: Английский

Citations

4
The molecular code of kidney cancer: A path of discovery for gene mutation and precision therapy DOI Creative Commons
Deqian Xie,

Guandu Li,

Zhonghua Zheng

et al.

Molecular Aspects of Medicine, Journal Year: 2025, Volume and Issue: 101, P. 101335 - 101335

Published: Jan. 1, 2025

Renal cell carcinoma (RCC) is a malignant tumor with highly heterogeneous and complex molecular mechanisms. Through systematic analysis of TCGA, COSMIC other databases, 24 mutated genes closely related to RCC were screened, including VHL, PBRM1, BAP1 SETD2, which play key roles in signaling pathway transduction, chromatin remodeling DNA repair. The PI3K/AKT/mTOR particularly important the pathogenesis RCC. Mutations such as PIK3CA, MTOR PTEN are associated metabolic abnormalities proliferation. Clinically, mTOR inhibitors VEGF-targeted drugs have shown significant efficacy personalized therapy. Abnormal regulation reprogramming, especially glycolysis glutamine pathways, provides cells continuous energy supply survival advantages, GLS1 promising results preclinical studies. This paper also explores potential immune checkpoint combination targeted drugs, well application nanotechnology drug delivery In addition, unique mechanisms revealed individualized therapeutic strategies explored for specific subtypes TFE3, TFEB rearrangement type SDHB mutant type. review summarizes common gene mutations their mechanisms, emphasizes diagnosis, treatment prognosis, looks forward prospects multi-pathway therapy, immunotherapy treatment, providing theoretical support clinical guidance new development.

Language: Английский

Citations

2
Vitamin B6 allosterically activates AMPK to promote postischemic angiogenesis in mice DOI
Xueqing Wang, Sen Yin, Qianwen Wang

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: 993, P. 177413 - 177413

Published: Feb. 21, 2025

Language: Английский

Citations

2
Neutrophils physically interact with tumor cells to form a signaling niche promoting breast cancer aggressiveness DOI

Sandra Camargo,

Ori Moskowitz,

Amir Giladi

et al.

Nature Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

Language: Английский

Citations

2
Growth factors: Bioactive macromolecular drugs for peripheral nerve injury treatment – Molecular mechanisms and delivery platforms DOI Open Access
Teng Wan, Fengshi Zhang,

Ming-Yu Qin

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 170, P. 116024 - 116024

Published: Dec. 19, 2023

Bioactive macromolecular drugs known as Growth Factors (GFs), approved by the Food and Drug Administration (FDA), have found successful application in clinical practice. They hold significant promise for addressing peripheral nerve injuries (PNIs). Peripheral guidance conduits (NGCs) loaded with GFs, context of tissue engineering, can ensure sustained efficient release these bioactive compounds. This, turn, maintains a stable, long-term, effective GF concentration essential treating damaged nerves. regeneration is complex process that entails secretion various GFs. Following PNI, GFs play pivotal role promoting cell growth survival, axon myelin sheath regeneration, differentiation, angiogenesis. also regulate regenerative microenvironment, stimulate plasticity changes post-nerve injury, and, consequently, expedite structure function repair. Both exogenous endogenous including NGF, BDNF, NT-3, GDNF, IGF-1, bFGF, VEGF, been successfully onto NGCs using techniques like physical adsorption, blend doping, chemical covalent binding, engineered transfection. These approaches effectively promoted repair Numerous studies demonstrated similar functional therapeutic outcomes compared to autologous transplantation. This evidence underscores substantial potential domain In this article, we provide an overview drug delivery systems utilizing NGCs. Looking ahead, commercial materials facilitate nerves maintain functionality distant target organs through

Language: Английский

Citations

26
Systemic inflammatory cytokine profiles in patients with gout during flare, intercritical and treat-to-target phases: TNFSF14 as new biomarker DOI
Hang‐Korng Ea, Brenda Kischkel,

T.W. Chirayath

et al.

Annals of the Rheumatic Diseases, Journal Year: 2024, Volume and Issue: 83(7), P. 945 - 956

Published: Feb. 19, 2024

Untreated gout is characterised by monosodium urate (MSU) crystal accumulation responsible for recurrent flares that are commonly separated asymptomatic phases. Both phases inflammatory conditions of variable intensity. Gout self-limited reactions involving multiple mediators. This study aimed to characterise the profiles at different

Language: Английский

Citations

17
Milestones in tumor vascularization and its therapeutic targeting DOI
Michele De Palma, Douglas Hanahan

Nature Cancer, Journal Year: 2024, Volume and Issue: 5(6), P. 827 - 843

Published: June 25, 2024

Language: Английский

Citations

17
Octopus‐Inspired Adaptive Molecular Motion for Synergistic Photothermal and Nitric Oxide Antibacterial Therapy in Diabetic Wound Repair DOI
Ziheng Chen,

Haitong Zhang,

Yuan Lyu

et al.

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: unknown

Published: July 1, 2024

Abstract Bacterial infections, especially those from drug‐resistant strains, pose a significant threat to healing diabetic skin injuries, with current treatments being intricated and often unsatisfactory. Inspired by octopuses, biomimetic material using α‐cyclodextrin (α‐CD) polyethylene glycol (PEG) assembled graphene oxide end‐capped polyrotaxanes (GO‐PR) is developed, where α‐CD mimics the flexible tentacles of an octopus. Further, cationically modified polyethyleneimine (PEI) resemble octopus suction cups, creating GO‐PRP, which effectively captures adheres bacteria. Importantly, emulate octopus's ink defense, GO‐PRP used as carrier for nitric (NO), resulting in GO‐PRP/NONOate. Utilizing photothermal conversion GO, near‐infrared light exposure triggers rapid heating NO release, providing efficient antibacterial activity biofilm dispersion, significantly reducing inflammation injuries type I rats. During wound healing, sustained release promotes vascular endothelial growth factor production blood vessel regeneration, enhancing collagen formation shortening time infections. Thus, octopus‐inspired GO‐PRP/NONOate emerges novel biomaterial treating bacterial infections wounds biomedical field.

Language: Английский

Citations

17
Natural-product-based, carrier-free, noncovalent nanoparticles for tumor chemo-photodynamic combination therapy DOI Creative Commons
Zhonglei Wang, Liyan Yang

Pharmacological Research, Journal Year: 2024, Volume and Issue: 203, P. 107150 - 107150

Published: March 21, 2024

Cancer, with its diversity, heterogeneity, and complexity, is a significant contributor to global morbidity, disability, mortality, highlighting the necessity for transformative treatment approaches. Photodynamic therapy (PDT) has aroused continuous interest as viable alternative conventional cancer treatments that encounter drug resistance. Nanotechnology brought new advances in medicine shown great potential delivery treatment. For precise efficient therapeutic utilization of such tumor approach high spatiotemporal selectivity minimal invasiveness, carrier-free noncovalent nanoparticles (NPs) based on chemo-photodynamic combination essential. Utilizing natural products foundation nanodrug development offers unparalleled advantages, including exceptional pharmacological activity, easy functionalization/modification, well biocompatibility. The natural-product-based, carrier-free, NPs revealed excellent synergistic anticancer activity comparison free photosensitizers bioactive products, representing an favorable avenue improve efficacy. Herein, comprehensive summary current strategies representative application examples past decade (such paclitaxel, 10-hydroxycamptothecin, doxorubicin, etoposide, combretastatin A4, epigallocatechin gallate, curcumin) therapy. We highlight insightful design synthesis smart aim enhance PDT Meanwhile, we discuss future challenges opportunities associated these provide enlightenment, spur innovative ideas, facilitate PDT-mediated clinical transformation.

Language: Английский

Citations

15