ObjectiveThis study aims to observe the effect of sinomenine （SIN） on fatty acid binding protein 4 （FABP4） in synovial tissue of rats with osteoarthritis （OA） and investigate the therapeutic mechanism of SIN on OA， further providing new ideas for the management of osteoarthritis by traditional Chinese medicine （TCM）. MethodsAn OA rat model was constructed and randomly divided into a control group， an OA group， an OA + SIN-L group （50 mg·kg^-1）， an OA + SIN-M （100 mg·kg^-1）， an OA + SIN-H （200 mg·kg^-1）， and an OA + prednisone （PDN） group （5 mg·kg^-1）. Following surgical modeling for three weeks， an appropriate medication was administered for four weeks. During modeling and administration， a hot plate test was performed to detect the pain and swelling of the knee joints of the rats. The periarticular tissue was collected for arthropathological observation at the end of drug administration. The expression of cleaved Caspase-3， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， and FABP4 in the synovial tissue of rats was detected by Western blot and real-time quantitative polymerase chain reaction （Real-time PCR）， and the expression and distribution of FABP4 protein in the synovial membrane were detected by immunofluorescence. ResultsCompared with those in the control group， the levels of inflammatory factors and FABP4 in the serum of rats in the OA group were significantly increased （P<0.05， P<0.01）， and joint swelling was significantly elevated （P<0.01）. The thermal pain threshold was significantly reduced （P<0.01）， and the expression of FABP4 protein and the fluorescence intensity were significantly increased （P<0.01）. The synovial tissue exhibited significantly increased inflammatory infiltration， proliferated fibroblasts， and an elevated apoptotic index （P<0.05， P<0.01）. Compared with those in the OA group， the serum lipid metabolism indexes of rats in the SIN administration group gradually returned to normal （P<0.05， P<0.01）， while the levels of inflammatory factors and FABP4 in the serum of rats in the SIN-administered group were significantly reduced （P<0.05， P<0.01）， and joint swelling was significantly decreased （P<0.05， P<0.01）. The thermal pain threshold was significantly elevated （P<0.05， P<0.01）， and the expression of FABP4 protein and fluorescence intensity in the synovial tissue were significantly decreased （P<0.05， P<0.01）. The synovial tissue displayed significantly reduced inflammatory infiltration and a decreased apoptotic index （P<0.05， P<0.01）. ConclusionThe therapeutic effect of SIN on OA may be related to the down-regulation of FABP4 expression， reduction of apoptosis， and inhibition of inflammatory factor expression.

The original version of this article (Yang et al., 2023) unfortunately contained a mistake. In Acknowledgments, the funding information for the Zhejiang Provincial Natural Science Foundation of China (No. LBY21H160001) was wrong. The correct funding should be the Zhejiang Health Science and Technology Project (No. 2022KY682), China.

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

RNA-based gene therapy has been widely used for various diseases, and extensive studies have proved that suitable delivery routes greatly help the development of RNA therapeutics. Identifying a safe and effective delivery system is key to realizing RNA therapeutics' clinical translation. Inhalation is a non-invasive pulmonary delivery modality that can enhance the retention of therapeutic agents in the lungs with negligible toxicity, thereby improving patient compliance. Inhaled RNA therapeutics are increasingly becoming an area of focus for researchers; however, only several clinical trials have explored inhaled delivery of RNA for pulmonary diseases. This review presents an overview of recent advances in inhaled delivery systems for RNA therapeutics, including viral and nonviral systems, highlighting state of the art regarding inhalation in the messenger RNA (mRNA) field. We also summarize the applications of mRNA inhalants in infectious and other lung diseases. Simultaneously, the research progresses on small interfering RNAs (siRNAs), antisense oligonucleotides (ASOs), and different types of RNA are also discussed to provide new strategies for developing RNA inhalation therapy. Finally, we clarify the challenges inhaled RNA-based therapeutics face before their widespread adoption and provide insights to help advance this exciting field to the bedside.

Dental pulp-dentin complex defects remain a major unresolved problem in oral medicines. Clinical therapeutic methods including root canal therapy and vital pulp therapy are both considered as conservative strategies, which are incapable of repairing the pulp-dentin complex defects. Although biomaterial-based strategies show remarkable progress in antibacterial, anti-inflammatory, and pulp regeneration, the important modulatory effects of nerves within pulp cavity have been greatly overlooked, making it challenging to achieve functional pulp-dentin complex regeneration. In this study, we propose an injectable bioceramics-containing composite hydrogel in combination of Li-Ca-Si (LCS) bioceramics and gelatin methacrylate matrix with photo-crosslinking properties. Due to the sustained release of bioactive Li, Ca and Si ions from LCS, the composite hydrogels possess multiple functions of promoting the neurogenic differentiation of Schwann cells, odontogenic differentiation of dental pulp stem cells, and neurogenesis-odontogenesis couples in vitro. In addition, the in vivo results showed that LCS-containing composite hydrogel can significantly promote the pulp-dentin complex repair. More importantly, LCS bioceramics-containing composite hydrogel can induce the growth of nerve fibers, leading to the re-innervation of pulp tissues. Taken together, the study suggests that LCS bioceramics can induce the innervation of pulp-dentin complex repair, offering a referable strategy of designing multifunctional filling materials for functional periodontal tissue regeneration.
Dental Pulp/drug effects* ; Hydrogels/pharmacology* ; Animals ; Ceramics/pharmacology* ; Dentin/drug effects* ; Biocompatible Materials/pharmacology* ; Rats ; Gelatin ; Regeneration/drug effects* ; Cell Differentiation/drug effects* ; Injections ; Humans ; Odontogenesis/drug effects*

Lophatheri Herba (Danzhuye in Chinese) is derived from the dried stems and leaves of Lophatherum gracile and has a long history of use as a medicinal and food source. Flavonoids and phenolic acids are the main active ingredients in Lophatheri Herba, which produce diuretic, anti-inflammatory, and antipyretic effects. Flavonoid glycosides and hydroxybenzoic acids are respectively the main structure in 44 flavonoids and 16 phenolic acids obtained from Lophatheri Herba. Modern pharmacological studies have found that the main chemical constituents of Lophatheri Herba play important roles in anti-inflammatory, cardioprotective, hepatoprotective and hypoglycaemic effects. Studies have demonstrated that flavonoid monomers, for example, luteolin, isoorientin, luteolin-7-O-β-D-glucoside and apigenin are more effective in exerting the above pharmacological effects. In addition, Lophatheri Herba is used in different food products as the main ingredient or as an accessory. This review describes Lophatheri Herba in terms of its chemical composition, pharmacological effects and efficacy, food development and applications, and clinical utility, and discusses the problems facing its use. This study provides valuable ideas and a scientific basis for the future development and use of L. gracile.

Acute ischemic stroke (AIS) is a cerebrovascular disease characterized by high morbidity, disability, and mortality, posing a significant threat to human health. Endovascular treatment has now been established as a key method for AIS management, in which stent retrievers that can mechanically remove blood clots play a key role in this technique. In recent years, stent retrievers have evolved in complexity and functionality to improve the ability of clot removing and surgical safety. However, the present instruments still have limitations on treatment efficiency, vascular adaptability, and operational precision, posing an urgent need for innovation in the design of stent retrievers. This paper systematically reviewed the structural features and working principles of AIS stent retrievers from the perspective of efficacy evaluation metrics, historical development, recent advancements in stent retrieval technology, and future prospects.
Humans ; Ischemic Stroke/surgery* ; Stents ; Endovascular Procedures/methods* ; Thrombectomy/methods* ; Device Removal/methods*

AIM:To investigate the effects of adipose-derived stem cells(ADSCs)with overexpression or si-lencing of long noncoding RNA(lncRNA)SNHG8 on the viability,migration,angiogenesis,and the expression of vasoac-tive factors in human umbilical vein endothelial cells(HUVECs).METHODS:Identification of ADSCs derived from morbidly obese patients(O-ADSCs)was conducted using flow cytometry and induction of lipogenesis and osteogenesis.The expression of lncRNA SNHG8 in healthy human ADSCs(H-ADSCs)and O-ADSCs was detected by RT-qPCR.Tran-swell method was used to establish the indirect co-culture system of ADSCs and HUVECs for 48 h,and the cells were di-vided into O-ADSCs+HUVECs group,H-ADSCs+HUVECs group,and HUVECs alone group.The mRNA and protein ex-pression levels of angiotensin Ⅱ(Ang Ⅱ),endothelin-1(ET-1)and endothelial nitric oxide synthase(eNOS)in HUVECs were detected by RT-qPCR and Western blot.The lncRNA SNHG8 overexpression and silencing lentiviruses were con-structed and used to infect O-ADSCs.The indirect co-cultured ADSCs and HUVECs were divided into O-ADSCs-OE-SNHG8+ HUVECs group,O-ADSCs-OE-NC+HUVECs group,O-ADSCs-sh-SNHG8+HUVECs group,and O-ADSCs-sh-NC+HUVECs group.After co-culture for 48 h,the viability,migration and tubule formation of HUVECs were detected by CCK-8,scratch and angiogenesis assays,respectively.The mRNA and protein expression levels of Ang Ⅱ,ET-1 and eNOS in HU-VECs were detected by RT-qPCR and Western blot,respectively.The nitrate reductase method was used to detect the con-tent of NO in HUVECs.RESULTS:(1)The cultured cells were identified as ADSCs.(2)Compared with H-ADSCs,ln-cRNA SNHG8 expression was significantly up-regulated in O-ADSCs(P<0.01).(3)Compared with H-ADSCs+HUVECs group and HUVECs group,the mRNA and protein expression levels of Ang Ⅱ and ET-1 in HUVECs in O-ADSCs+HU-VECs group were up-regulated(P<0.01).(4)Overexpression of lncRNA SNHG8 in O-ADSCs enhanced the viability,mi-gration and tube formation ability of HUVECs,up-regulated the mRNA and protein expression levels of Ang Ⅱ and ET-1,down-regulated the mRNA and protein expression levels of eNOS,and decreased the content of NO in HUVECs(P<0.05).However,silencing of lncRNA SNHG8 in O-ADSCs exerted opposite results(P<0.05).CONCLUSION:(1)The O-ADSCs can promote endothelial cell viability,migration and tubule formation through paracrine effects.(2)The O-ADSCs with overexpression of lncRNA SNHG8 promote the imbalance of diastolic and contractile factors secreted by endo-thelial cells,and induce the dysfunction of vascular endothelial cells.

Objective To comapre and analyze the differences and commonalities of expression profiles of serum exosomal microRNA between patients with thyroid nodules and healthy persons at different iodine levels,and then provide evidence for screening early diag-nostic markers of thyroid nodules at different iodine levels.Methods The peripheral blood samples from 10 patients with thyroid nod-ules and healthy volunteers at different iodine levels were collected.Their serum iodine levels were measured by the arsenic cerium cat-alytic spectrophotometry.Serum exosomal microRNA were extracted and the expression levels of microRNA were determined by the high-throughput sequencing technology.The differential target genes were predicted and further performed Gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis.Results Compared with healthy volunteers,there were 6 downreg-ulated miRNAs in the patients with thyroid nodules at different iodine levels,namely miR-324-5p,miR-6511b-3p,miR-9903,miR-550a-3p,miR-5001-3p,and miR-3688-3p.Differentially expressed exosomal microRNA could regulate the MAPK signaling path-way,PI3K-AKT signaling pathway,VEGF signaling pathway,and NF-κB signaling pathway.Conclusion Six differentially expressed microRNAs is identified,which may serve as biological markers for the early diagnosis of thyroid nodules at different iodine levels.