Background: Tibia fracture (BF) before stroke shortly causes long-term post-stroke memory dysfunction in mice. The mechanism is unclear. We hypothesize that BF enhances neuroinflammation and blood brain barrier (BBB) breakdown in the hippocampus and white matter (WM) damage. Methods: Mice were assigned to groups: BF, stroke, BF+stroke (BF 6 h before stroke) and sham. BBB integrity was analyzed 3 days after the surgeries and WM injury was analyzed 3 days and 8 weeks after the surgeries. Results: Stroke and BF+stroke groups had more activated microglia/macrophages and lower levels of claudin-5 in the ipsilateral hippocampi than the BF group. BF+stroke group had the highest number microglia/macrophages and the lowest level of claudin-5 among all groups and had fewer pericytes than BF group. Stroke and BF+stroke groups had smaller WM areas in the ipsilateral basal ganglia than the sham group 8 weeks after the injuries. The BF+stroke group also had smaller WM areas in the ipsilateral than sham and BF groups 3 days after the injuries and in the contralateral basal ganglia than stroke and BF groups 8 weeks after the injuries. Conclusions: BF exacerbates neuroinflammation and BBB leakage in the hippocampus and WM damage in basal ganglia, which could contribute to the long-lasting memory dysfunction in BF+stroke mice.

This study aimed to explore the regulatory effects and associated mechanisms of adiponectin on apoptosis and proliferation in the LN18 glioma cell line through the AMPK and Akt signaling pathways. Additionally, we sought to elucidate the impact of adiponectin on the chemosensitivity of the LN18 glioma cell line to temozolomide (TMZ). The proliferation rate of glioma cells treated with adiponectin was assessed using the cholecystokinin (CCK8) assay. The Western blot analysis was employed to assess the expression of p-Akt, p-AMPK, p-mTOR, cleaved caspase3, Bax, Cyclin D1, and Cyclin B1 following adiponectin treatment. Cell apoptosis was quantified using AnnexinV/PI flow cytometry, while changes in the cell cycle were detected using PI staining flow cytometry. The findings revealed that adiponectin upregulates p-AMPK expression and downregulates p-mTOR expression in the PTEN wild-type glioma cell line LN18, with no discernible effect on p-Akt expression. Moreover, adiponectin inhibits the proliferation rate of the PTEN wild-type glioma cell line LN18, enhances the expression of cleaved caspase3 and Bax, and significantly elevates the apoptosis rate, as evidenced by AnnexinV/PI flow cytometry. Adiponectin was observed to suppress the expression of Cyclin D1 and Cyclin B1, increase the number of cells in the G1 phase, and promote autophagy. Additionally, adiponectin augments the expression of Beclin1 and the ratio of LC3II/I in the PTEN wild-type glioma cell line LN18, while decreasing p62 expression. In conclusion, this study posits that adiponectin holds therapeutic promise for glioma treatment. Furthermore, adiponectin enhances the inhibitory effect of TMZ on the proliferation rate of LN18 cells when treated with 0.1 mM and 1 mM TMZ. These results collectively suggest that adiponectin impedes proliferation, encourages apoptosis and autophagy in the LN18 glioma cell line, and heightens its sensitivity to the chemotherapeutic drug TMZ.

Stroke is a major outcome of cardiovascular–kidney–metabolic (CKM) syndrome, but evidence on the longitudinal interplay between metabolic dysfunction and systemic inflammation remains limited. We analyzed 4,614 participants with early-stage CKM syndrome from the China Health and Retirement Longitudinal Study (CHARLS). The triglyceride–glucose waist-to-height ratio (TyG-WHtR) and high-sensitivity C-reactive protein (hs-CRP) were measured in 2011 and 2015. Latent class mixed models identified distinct short-term trajectories, and Cox regression estimated hazard ratios (HRs) for incident stroke and all-cause mortality from 2015 to 2020. During follow-up, 445 strokes and 164 deaths occurred. Higher baseline TyG-WHtR (HR, 1.57; 95% CI, 1.26–1.97) and hs-CRP (HR for Q4 vs. Q1, 1.67; 95% CI, 1.06–2.64) predicted greater stroke risk, while associations with mortality were weaker. Participants with both markers elevated had the highest stroke risk (HR, 1.83; 95% CI, 1.38–2.44). Trajectory analyses identified three distinct patterns for each biomarker. Compared with the low-stable group, high TyG-WHtR (HR, 1.87; 95% CI, 1.32–2.63) and high hs-CRP (HR, 1.49; 95% CI, 1.15–1.91) trajectories conferred significantly increased stroke risk. Joint trajectory analysis showed that participants with persistently elevated hs-CRP and historically high TyG-WHtR (Class 3) had the greatest risk (HR, 1.66; 95% CI, 1.22–2.26), whereas Class 2 (moderate and rising levels) did not differ significantly from the low-risk group. No trajectory was significantly associated with mortality. Both baseline and unfavorable short-term trajectories of TyG-WHtR and hs-CRP independently predict stroke but not all-cause mortality in early CKM populations. Concurrent metabolic and inflammatory burden markedly amplifies cerebrovascular risk, underscoring the importance of dynamic biomarker monitoring for early risk stratification and precision prevention.

Background: Mild cognitive impairment (MCI) and dementia are global health challenges. Abdominal obesity, measured by the conicity index (CI), has been linked to cognitive impairment, yet longitudinal studies exploring its impact on cognitive trajectories remain limited. This study examines the association between CI and cognitive trajectories in two diverse cohorts and evaluates whether abdominal obesity represents a modifiable risk factor. Method: This retrospective cohort study utilized data from the Xi’an Rural Resident Cognitive Cohort (XRRCC) and the U.S. Health and Retirement Study (HRS). Participants with normal baseline cognitive function and at least four waves of data (2014–2020) were included. Abdominal obesity was quantified using CI and categorized into quartiles. Latent class growth models (LCGMs) identified cognitive trajectories, and multinomial logistic regression analyzed the association between CI quartiles and trajectories, adjusting for demographic, lifestyle, and clinical variables. Subgroup analyses assessed variations by age, sex, and comorbidities. Result: In the XRRCC cohort ( n = 1,452), two cognitive trajectories were identified: persistently stable (90.2%) and gradually deteriorating (9.2%). In the HRS cohort ( n = 4,494), three trajectories were observed: persistently high (35.1%), persistently moderate (51.4%), and gradually deteriorating (13.5%). Higher CI values were associated with worse cognitive trajectories in both cohorts. Fully adjusted models showed that participants in the highest CI quartile had greater odds of cognitive decline compared to the lowest quartile (XRRCC: OR = 0.554, 95% CI: 0.328–0.938; HRS: OR = 0.725, 95% CI: 0.611–0.861). Subgroup analyses revealed stronger associations among women and younger participants (<65 years). Conclusion: Higher CI values are linked to worse cognitive trajectories, particularly in women and younger individuals. These findings highlight abdominal obesity as a potential modifiable risk factor for cognitive decline and support early interventions targeting central obesity to mitigate cognitive deterioration.