Bo He

Background: Cerebrovascular diseases have complex pathogenesis and pose a serious threat to human health; thus, novel diagnostic and therapeutic strategies are needed. Small extracellular vesicles (sEVs), commonly referred to as exosomes, are 30–150 nm lipid-bilayer vesicles that shield long noncoding RNAs (lncRNAs) from degradation. Because exosomal lncRNAs are more stable than free lncRNAs in blood and cerebrospinal fluid and can cross the blood–brain barrier, they are promising as biomarkers and therapeutic vectors. This review summarizes the roles and mechanisms of exosomal lncRNAs in cerebrovascular diseases. Methods: This narrative review is based on the experimental literature and focuses on the biological functions and regulatory mechanisms of exosomal lncRNAs in cerebrovascular disorders. Results: As competing endogenous RNAs (ceRNAs), they sequester microRNAs (miRNAs), thereby derepressing downstream target-gene expression and modulating neuronal injury (oxidative stress, apoptosis, neuroinflammation) through the nuclear factor kappa-B (NF-κB) and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathways. They show altered profiles in acute stroke (ischemic/hemorrhagic) correlated with neurological deficits, and are relevant to the early diagnosis of chronic diseases (atherosclerosis, aneurysm) and vascular dementia. Conclusions: Exosomal lncRNAs demonstrate promising translational potential in preclinical studies because they combine exosome delivery capabilities with lncRNA regulatory functions, although clinical validation remains limited.

20( R )‐ginsenoside Rg3 can reduce the effects of oxidative stress and cell death in cerebral ischemia‒reperfusion injury (CIRI). Neuroinflammation is crucial post‐CIRI, but how 20( R )‐Rg3 affects ischemia‒reperfusion‐induced neuroinflammation is unclear. To study 20( R )‐Rg3's effects on neuroinflammation and neuronal preservation in stroke models and explore toll‐like receptor 4/myeloid differentiation factor‐88/nuclear factor kappa B (TLR4/MyD88/NF‐κB) pathway mechanisms. Middle cerebral artery occlusion/reperfusion (MCAO/R) rats and oxygen–glucose deprivation/reoxygenation (OGD/R)‐induced neuron injury were treated with 20( R )‐Rg3; survival, cytokine levels, and pathway protein expressions were assessed; efficacy with the TLR4 inhibitor was also evaluated. In MCAO/R rats, 20( R )‐Rg3 administration reduced inflammatory damage to brain tissue. 20( R )‐Rg3 dose‐dependently improved neuronal survival and attenuated inflammatory processes in OGD/R neurons. The expression levels of TLR4, MyD88, and phosphorylated NF‐κB p65 are upregulated in MCAO/R rat brain tissue and OGD/R‐induced neurons, and these effects are reversed by 20( R )‐Rg3 treatment. In addition, 20( R )‐Rg3 enhanced the anti‐inflammatory efficacy of the TLR4 inhibitor TAK‐242 and reduced inflammation in OGD/R‐exposed neurons. 20( R )‐Rg3 attenuates neuroinflammation and protects neurons via inhibiting TLR4/MyD88/NF‐κB pathway in vitro and in vivo, suggesting it is a potential therapeutic for ischemic stroke.

Ginseng saponins (ginsenosides), bioactive compounds derived from ginseng, are widely used natural products with potent therapeutic properties in the management of various ailments, particularly tumors, cardiovascular and cerebrovascular diseases, and immune system disorders. Autophagy, a highly regulated and multistep process involving the breakdown of impaired organelles and macromolecules by autophagolysosomes and autophagy‐related genes (ATGs), has gained increasing attention as a potential target for ginsenoside‐mediated disease treatment. This review aims to provide a comprehensive overview of recent research advances in the understanding of autophagy‐related signaling pathways and the role of ginsenoside‐mediated autophagy regulation. By delving into the intricate autophagy signaling pathways underpinning the pharmacological properties of ginsenosides, we highlight their therapeutic potential in addressing various conditions. Our findings serve as a comprehensive reference for further investigation into the medicinal properties of ginseng or ginseng‐related products.

Reducing mitochondrial oxidative stress has become an important strategy to prevent neuronal death in ischemic stroke. Previous studies have shown that 20(R)‐ginsenoside Rg3 can significantly improve behavioral abnormalities, reduce infarct size, and decrease the number of apoptotic neurons in cerebral ischemia/reperfusion injury rats. However, it remains unclear whether 20(R)‐ginsenoside Rg3 can inhibit mitochondrial oxidative stress in ischemic stroke and the potential molecular mechanism. In this study, we found that 20(R)‐ginsenoside Rg3 notably inhibited mitochondrial oxidative stress in middle cerebral artery occlusion/reperfusion (MCAO/R) rats and maintained the stability of mitochondrial structure and function. Treatment with 20(R)‐ginsenoside Rg3 also decreased the levels of mitochondrial fission proteins (Drp1 and Fis1) and increased the levels of fusion proteins (Opa1, Mfn1, and Mfn2) in MCAO/R rats. Furthermore, we found that 20(R)‐ginsenoside Rg3 promoted nuclear aggregation of nuclear factor erythroid2‐related factor 2 (Nrf2) but did not affect Kelch‐like ECH‐associated protein‐1 (Keap1), resulting in the downstream expression of antioxidants. In in vitro oxygen‐glucose deprivation/reperfusion stroke models, the results of PC12 cells treated with 20(R)‐ginsenoside Rg3 were consistent with animal experiments. After transfection with Nrf2 short interfering RNA (siRNA), the protective effect of 20(R)‐ginsenoside Rg3 on PC12 cells was reversed. In conclusion, the inhibition of mitochondrial oxidative stress plays a vital position in the anti‐cerebral ischemia‐reperfusion injury of 20(R)‐ginsenoside Rg3, and its neuroprotective mechanism is related to the activation of the nuclear factor erythroid2‐related factor 2/heme oxygenase 1 signaling pathway.

We studied the pathological anatomical structures of atypical Wassel Type VI thumb duplication to provide a theoretical basis for surgical treatment. Forty-seven patients with atypical Wassel Type VI thumb duplication were treated. We found that some of cases had an ulnar thumb without an extensor tendon, or without a flexor tendon, or without both. All the ulnar metacarpal bones were abnormal to variable degrees. On-top-plasty is currently the best procedure for the treatment of this type of anomaly. Flexor tendon reconstruction is an important factor in functional reconstruction of the thumb, and keeping the pulley and sheath intact is a key step in flexor tendon reconstruction. Placing the on-top-plasty level at the distal end of the metacarpal or at the proximal phalanx depends on the presence of the flexor tendon. According to the condition of the flexor tendon, the atypical Wassel Type IV duplication can be divided into two types: the absent type and the intact type. Level of evidence: VI

MicroRNAs (miRNAs) are a class of small, endogenous, noncoding RNAs. Recent research has proven that miRNAs play an essential role in the occurrence and development of ischemic stroke. Our previous studies confirmed that 20(R)-ginsenosideRg3 [20(R)-Rg3] exerts beneficial effects on cerebral ischemia–reperfusion injury (CIRI), but its molecular mechanism has not been elucidated. In this study, we used high-throughput sequencing to investigate the differentially expressed miRNA and mRNA expression profiles of 20(R)-Rg3 preconditioning to ameliorate CIRI injury in rats and to reveal its potential neuroprotective molecular mechanism. The results show that 20(R)-Rg3 alleviated neurobehavioral dysfunction in MCAO/R-treated rats. Among these mRNAs, 953 mRNAs were significantly upregulated and 2602 mRNAs were downregulated in the model group versus the sham group, whereas 437 mRNAs were significantly upregulated and 35 mRNAs were downregulated in the 20(R)-Rg3 group in contrast with those in the model group. Meanwhile, the expression profile of the miRNAs showed that a total of 283 differentially expressed miRNAs were identified, of which 142 miRNAs were significantly upregulated and 141 miRNAs were downregulated in the model group compared with the sham group, whereas 34 miRNAs were differentially expressed in the 20(R)-Rg3 treatment group compared with the model group, with 28 miRNAs being significantly upregulated and six miRNAs being significantly downregulated. Furthermore, 415 (391 upregulated and 24 downregulated) differentially expressed mRNAs and 22 (17 upregulated and 5 downregulated) differentially expressed miRNAs were identified to be related to 20(R)-Rg3′s neuroprotective effect on stroke recovery. The Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that 20(R)-Rg3 could modulate multiple signaling pathways related to these differential miRNAs, such as the cGMP-PKG, cAMP and MAPK signaling pathways. This study provides new insights into the protective mechanism of 20(R)-Rg3 against CIRI, and the mechanism may be partly associated with the regulation of brain miRNA expression and its target signaling pathways.