Salvianolate lyophilized injection (SLI) has been clinically used in China for the treatment of acutely cerebral infarction. Clinical and experimental studies have shown that Diabetes mellitus (DM) not only increases the risk of ischemic stroke recurrence but also leads to poor outcomes and increases fatality rates after stroke. Our previous study has proved that SLI can reduce the infarct volume after stroke in type 1 diabetic rats. The aim of the study is to explore the mechanism of SLI on stroke outcome in type 1 diabetic (T1DM) rats. Type 1 diabetes rats model (T1DM) was induced in male Wistar rats by intraperitoneal (i.p) injection of streptozotocin (60 mg/kg) and T1DM rats were subjected to intraluminal middle cerebral artery occlusion (MCAO). The T1DM + MCAO rats were randomly divided into six groups: sham-operated, model-vehicle, positive control group (Edaravone-treating, DE 6 mg/kg) and SLI-treating group (10.5 mg/kg, 21 mg/kg and 42 mg/kg). SLI and DE were administered by tail vein injection at 3 h after MCAO, then daily for 14 days. Micro-CT scans of the brain tissue revealed vessel characteristics and distribution in the ischemia zone. Glucose uptake was analyzed by PET/CT. RAGE, MMP9 and inflammatory factors (COX-2, TNF-α and ICAM-1), HQ-1, HQO-1 and Nrf-2 expression levels in the ischemic brain tissue were analyzed by Immunofluorescence staining and Western blot at 14 days after MCAO. In this study, we have demonstrated that SLI treatment significantly increased the number of brain microvasculature in ipsilateral and glucose uptake in cortex, hippocampus and penumbra in the T1DM + MCAO rats. SLI also significantly decreased the expression of RAGE, MMP9 and inflammatory factors expression, and increased the expression of HQ-1, HQO-1 and Nrf-2 in T1DM + MCAO rats. The study showed that SLI could protect against cerebral ischemia injury in T1DM + MCAO rats and the mechanism is related to decrease inflammatory factors and activate of the Nrf2/HO-1 signaling pathway.

Parkinson’s disease (PD) is a chronic neurodegenerative disorder characterized by a loss of dopaminergic neurons in the substantia nigra, decreased striatal dopamine levels, and consequent extrapyramidal motor dysfunction. The purpose of this study was to investigate potential in vivo protective effects of Duzhong against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), as well as the bioactive constituents against 1-methyl-4-phenylpyridinium (MPP+) toxicity in vitro. Male C57BL/6 mice were intraperitoneally administrated five consecutive injections of MPTP every 24 h at a dose of 30 mg/kg to induce an in vivo PD model. Pole and traction tests were performed in mice to evaluate motor deficits and bradykinesia after the final MPTP administration. The striatal levels of dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanilic acid, were measured using a High-performance liquid chromatography-electrical conductivity detector. To further explore the bioactive constituents and protective mechanisms of Duzhong, seven compounds from Duzhong were tested on MPP+-treated SH-SY5Y cell lines in vitro. A proteasome enzymatic assay and Cell Counting Kit-8 were performed to examine proteasomal activity and cell viability of Duzhong-treated cells, respectively, after exposure to MPP+ and proteasome inhibitor MG132. Duzhong antagonized the loss of striatal neurotransmitters and relieved the associated anomaly in ambulatory locomotor activity in PD mice after a 3-day pre-treatment of Duzhong crude extract. The five Duzhong compounds attenuated MPP+-induced dysfunction of protease activity and reduced MG132-induced cytotoxicity. Duzhong could serve as a potential candidate for PD treatment, and its mechanism involves the amelioration of the ubiquitin-proteasome system.

Background and Purpose: Blood-brain barrier (BBB) disruption following ischemic stroke (IS) contributes to hemorrhagic transformation, brain edema, increased neural dysfunction, secondary injury, and mortality. The prevailing view attributes the destruction of tight junction proteins (TJs) to the resulting BBB damage following IS. However, recent studies define a stepwise impairment of the transcellular barrier followed by the paracellular barrier which accounts for the BBB leakage in IS. The increased endothelial transcytosis that has been proven to be caveolae-mediated, preceding and independent of TJs disintegration. Emerging experimental investigations suggested Storax attenuates BBB damage after stroke. This study aimed to test our hypothesis that Storax inhibits caveolae-mediated transcytosis at BBB after ischemic stroke in rats.Methods: Male Wistar rats (250–300 g) were subjected to transient middle cerebral artery occlusion (t-MCAO). Brain water content and the cerebral infarction size were assessed by brain tissue drying-wet method and 2,3,5-triphenyltetrazolium chloride (TTC) staining. BBB permeability was detected by the leakage of Evans blue and Albumin-Alexa594. The ultrastructure of BBB was examined by transmission electron microscopy (TEM). Cav-1 and Mfsd2a were quantified by western blotting and immunofluorescence staining, AQP4, PDGFR-β, ZO-1 and Occludin were quantified by western blotting.Results: Storax treatment of 0.1 g/kg had no significant effects on brain lesions. Storax treatment of 0.2, 0.4, and 0.8 g/kg led to a significant decrease in infarction size, and the Storax 0.4, 0.8 g/kg groups displayed a significant reduction in brain water content. Storax treatment of 0.8 g/kg showed mild toxic reactions. Thus, 0.4 g/kg Storax was selected as the optimal dose for subsequent studies. Storax significantly inhibited the fluorescent albumin intensity in the brain parenchyma and the number of caveolae in ECs, alongside attenuating the ultrastructural disruption of BBB at 6 h after stroke. Meanwhile, Storax significantly increased the expression of Mfsd2a and PDGFR-β, and decrease the expression of Cav-1 and AQP4, corresponding to the significantly decreased Cav-1 positive cells and increased Mfsd2a positive cells. However, Storax has no significant effects on Evan blue leakage or the expression ZO-1, Occludin.Conclusion: Our experimental findings demonstrate Storax treatment inhibits caveolae-mediated transcytosis at BBB in the focal stroke model of rats. We also speculate that regulation of Cav-1, Mfsd2a, AQP4, and PDGFR-β expressions might be associated with its beneficial pharmacological effect, but remain to define and elucidate in future investigation.

Background: To study the corresponding strategies for controlling cancer in older adults aged 60 and above in China, a comprehensive assessment of disease burden is required. Therefore, we will introduce the cancer epidemiological characteristics of older adults in China over a recent 12 year period.Methods: The age-period-cohort model was constructed using the cancer incidence data from the Chinese Cancer Registry Annual Report published in 2008–2019. The annual change percentage (APC) was estimated by log-linear regression to reflect the time trend. The data from the GLOBOCAN 2020 database was selected for worldwide comparative analysis.Results: The cancer incidence in older adults aged 60 and above in China showed a decreasing trend (APC = −0.73%, P = 0.009). The urban/rural ratio of cancer incidence increased from 0.94 to 1.07 (t = 3.52, P < 0.05), while the sex ratio (male/female) showed a significant decreasing trend only in rural areas (t = −6.77, P < 0.05), and the ratio decreased from 2.02 to 1.72. The results of the age-period-cohort model showed that the cancer incidence increased with age in both males and females, urban and rural areas. The RR of period effect increased from 2005 to 2010, then decreased from 2010 to 2015, and the downward trend was more obvious. The RR of the later-born cohort was lower than that of the earlier-born cohort in rural areas. Lung, gastric, colorectal, esophageal, liver, and breast cancers were common cancers in Chinese older adults. Lung cancer incidence ranked first in males, and it decreased with time in the 75–79 and 80–84 age groups (APC_{75 − 79} = −1.10%, APC_{80 − 84} = −0.88%, all P < 0.05). Breast cancer incidence ranked first among female in the 60–64 age group and showed an increasing trend (APC_{60 − 64} = 1.52%, P < 0.05).Conclusions: The cancer incidence in Chinese older adults aged 60 and above showed a decreasing trend, but it was still at a relatively high level. The key targets of prevention and treatment should be males, urban areas, younger people, older adults aged 60–69, lung, gastrointestinal, and breast cancers in the future.

The microglia, displaying diverse phenotypes, play a significant regulatory role in the development, progression, and prognosis of Parkinson’s disease. Research has established that glycolytic reprogramming serves as a critical regulator of inflammation initiation in pro-inflammatory macrophages. Furthermore, the modulation of glycolytic reprogramming has the potential to reverse the polarized state of these macrophages. Previous studies have shown that Levistilide A (LA), a phthalide component derived from Angelica sinensis, possesses a range of pharmacological effects, including anti-inflammatory, antioxidant, and neuroprotective properties. In our study, we have examined the impact of LA on inflammatory cytokines and glucose metabolism in microglia induced by lipopolysaccharide (LPS). Furthermore, we explored the effects of LA on the AMPK/mTOR pathway and assessed its neuroprotective potential both in vitro and in vivo. The findings revealed that LA notably diminished the expression of M1 pro-inflammatory factors induced by LPS in microglia, while leaving M2 anti-inflammatory factor expression unaltered. Additionally, it reduced ROS production and suppressed IκB-α phosphorylation levels as well as NF-κB p65 nuclear translocation. Notably, LA exhibited the ability to reverse microglial glucose metabolism reprogramming and modulate the phosphorylation levels of AMPK/mTOR. In vivo experiments further corroborated these findings, demonstrating that LA mitigated the death of TH-positive dopaminergic neurons and reduced microglia activation in the ventral SNpc brain region of the midbrain and the striatum. In summary, LA exhibited neuroprotective benefits by modulating the polarization state of microglia and altering glucose metabolism, highlighting its therapeutic potential.