A Photolabile Curcumin-Diazirine Analogue Enables Phototherapy with Physically and Molecularly Produced Light for Alzheimer's Disease Treatment.

The development of Alzheimer's disease (AD) drugs has recently witnessed substantial achievement. To further enhance the pool of drug candidates, it is crucial to explore non-traditional therapeutic avenues. In this study, we present the use of a photolabile curcumin-diazirine analogue, CRANAD-147, to induce changes in properties, structures (sequences), and neurotoxicity of amyloid beta (Aß) species both in cells and in vivo. This manipulation was achieved through irradiation with LED light or molecularly generated light, dubbed as "molecular light", emitted by the chemiluminescence probe ADLumin-4. Next, aided by molecular chemiluminescence imaging, we demonstrated that the combination of CRANAD-147/LED or CRANAD-147/ADLumin-4 (molecular light) could effectively slow down the accumulation of Aßs in transgenic 5xFAD mice in vivo. Leveraging the remarkable tissue penetration capacity of molecular light, phototherapy employing the synergistic effect of a photolabile Aß ligand and molecular light emerges as a promising alternative to conventional AD treatment interventions.

[Effect of Polygonati Rhizoma in improving pyroptosis injury of diabetic macroangiopathy via NLRP3/caspase-1/GSDMD pathway].

This study aims to explore the influence of Polygonati Rhizoma on the pyroptosis in the rat model of diabetic macroangiopathy via the NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate specific proteinase-1(caspase-1)/gasdermin D(GSDMD) pathway. The rat model of diabetes was established by intraperitoneal injection of streptozotocin(STZ) combined with a high-fat, high-sugar diet. The blood glucose meter, fully automated biochemical analyzer, hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay, immunofluorescence, immunohistochemistry, and Western blot were employed to measure blood glucose levels, lipid levels, vascular thickness, inflammatory cytokine levels, and expression levels of pyroptosis-related proteins. The mechanism of pharmacological interventions against the injury in the context of diabetes was thus explored. The results demonstrated the successful establishment of the model of diabetes. Compared with the control group, the model group showed elevated levels of fasting blood glucose, total cholesterol(TC), triglycerides(TG) and low-density lipoprotein cholesterol(LDL-c), lowered level of high-density lipoprotein cholesterol(HDL-c), thickened vascular intima, and elevated serum and aorta levels of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß) and interleukin-18(IL-18). Moreover, the model group showed increased NLRP3 inflammasomes and up-regulated levels of caspase-1 and GSDMD in aortic vascular cells. Polygonati Rhizoma intervention reduced blood glucose and lipid levels, inhibited vascular thickening, lowered the levels of TNF-α, IL-1ß, IL-18 in the serum and aorta, attenuated NLRP3 inflammasome expression, and down-regulated the expression levels of caspase-1 and GSDMD, compared with the model group. In summary, Polygonati Rhizoma can slow down the progression of diabetic macroangiopathy by inhibiting pyroptosis and alleviating local vascular inflammation.

[Effect of acupuncture at the anterior oblique parietotemporal line on gray matter remodeling in patients with hemiplegia of cerebral infarction].

OBJECTIVE: To observe the intervention effect of acupuncture at the anterior oblique parietotemporal line on gray matter remodeling in patients with hemiplegia of cerebral infarction based on voxel-based morphology (VBM), and to reveal the advantages and central effect sites of scalp acupuncture for hemiplegia of cerebral infarction. METHODS: A total of 18 patients with hemiplegia of cerebral infarction in the right basal ganglia and 18 healthy subjects were enrolled and T1 structural scan was performed. The patients were randomly divided into scalp acupuncture group and non-scalp acupuncture group, with 9 patients in each group. SPSS20.0 was used to analyze the degree of neurological deficit (NIHSS) before and after treatment, and SPM8 software package was used to compare the change in gray matter after treatment between the two groups, the difference in gray matter between patients and healthy subjects. RESULTS: After treatment, the scalp acupuncture group had a significant reduction in NIHSS (P<0.05), while the non-scalp acupuncture group had no significant change in NIHSS (P>0.05); the scalp acupuncture group had a significantly lower NIHSS than the non-scalp acupuncture group after treatment (P<0.05). Compared with the healthy subjects, the patients with cerebral infarction had a voxel increase of gray matter in the bilateral cerebellum; after 2 weeks of treatment, the scalp acupuncture group had a voxel increase of gray matter in the motor-related cortex (such as the cerebellum, the anterior cingulate, the basal nucleus, and the medial frontal gyrus) and some parts of the sensory cortex, while the non-scalp acupuncture group had a slight voxel increase of gray matter in few brain regions which were not associated with motor. After treatment, the scalp acupuncture group had a voxel increase in the brain regions of the basal ganglia, mainly the lenticular nucleus and the claustrum. Compared with the non-scalp acupuncture group after treatment, the scalp acupuncture group had a greater gray matter increase in the brain regions mainly in the bilateral cerebellar cortex. CONCLUSION: Acupuncture at the anterior oblique parietotemporal line can promote neurological function recovery in patients with hemiplegia, possibly by promoting gray matter remodeling in the motor centers of the extrapyramidal system (mainly the bilateral cerebellum and the contralateral basal ganglia) and some parts of the sensory cortex and inducing functional compensation in corresponding brain regions.

Altered effective connectivity of resting state networks by acupuncture stimulation in stroke patients with left hemiplegia: A multivariate granger analysis.

The aim of this study was to explore the response feature of resting-state networks (RSNs) of stroke patients with left hemiplegia by acupuncture stimulation.Nineteen stroke patients with left hemiplegia and 17 controls were recruited in this study. Resting-state functional magnetic resonance imaging data before and after acupuncture were acquired using magnetic scanning. The independent component analysis (ICA) was employed to extract RSNs related to motion, sensation, cognition, and execution, including sensorimotor network (SMN), left and right frontoparietal network (LFPN and RFPN), anterior and posterior default mode network (aDMN, pDMN), visual network (VN), and salience network (SN). Granger causality method was used to explore how acupuncture stimulation affects the causality between intrinsic RSNs in stroke patients. Compared with healthy subjects, stroke patients presented the more complex effective connectivity. Before acupuncture stimulation, LFPN inputted most information from other networks while DMN outputted most information to other networks; however, the above results were reversal by acupuncture. In addition, we found aDMN reside in between SMN and LFPN after acupuncture.The finding suggested that acupuncture probably integrated the effective connectivity internetwork by modulating multiple networks and transferring information between LFPN and SMN by DMN as the relay station.

[Imaging Observation of Scalp Acupuncture on Brain Gray Matter Injury in Stroke Patients with Cerebral Infarction].

OBJECTIVE: To study features of brain gray matter injury in cerebral infarction patients and intervention of scalp acupuncture by using voxel-based morphology. METHODS: A total of 16 cerebral infarction patients were recruited in this study, and assigned to the scalp acupuncture group and the control group, 8 in each group. Another 16 healthy volunteers were recruited as a normal group. All patients received scanning of T1 structure. Images were managed using VBM8 Software package. Difference of the gray matter structure was compared among the scalp acupuncture group, the control group, and the healthy volunteers. RESULTS: Compared with healthy volunteers, gray matter injury of cerebral infarction patients mainly occurred in 14 brain regions such as cingulate gyrus, precuneus, cuneus, anterior central gyrus, insular lobe, and so on. They were mainly distributed in affected side. Two weeks after treatment when compared with healthy volunteers, gray matter injury of cerebral infarction patients in the scalp acupuncture group still existed in 8 brain regions such as bilateral lingual gyrus, posterior cingulate gyrus, left cuneus, right precuneus, and so on. New gray matter injury occurred in lingual gyrus and posterior cingulate gyrus. Two weeks after treatment when compared with healthy volunteers, gray matter injury of cerebral infarction patients in the control group existed in 23 brain regions: bilateral anterior cingulum, caudate nucleus, cuneate lobe, insular lobe, inferior frontal gyrus, medial frontal gyrus, precuneus, paracentral lobule, superior temporal gyrus, middle temporal gyrus, lingual gyrus, right postcentral gyrus, posterior cingulate gyrus, precentral gyrus, middle frontal gyrus, and so on. New gray matter injury still existed in 9 cerebral regions such as lingual gyrus, posterior cingulate gyrus, postcentral gyrus, and so on. CONCLUSIONS: Brain gray matter structure is widely injured after cerebral infarction. Brain gray matter volume gradually decreased as time went by. Combined use of scalp acupuncture might inhibit the progression of gray matter injury more effectively.

Imaging Observation of Scalp Acupuncture on Brain Gray Matter Injury in Stroke Patients with Cerebral Infarction / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study features of brain gray matter injury in cerebral infarction patients and intervention of scalp acupuncture by using voxel-based morphology.</p><p><b>METHODS</b>A total of 16 cerebral infarction patients were recruited in this study, and assigned to the scalp acupuncture group and the control group, 8 in each group. Another 16 healthy volunteers were recruited as a normal group. All patients received scanning of T1 structure. Images were managed using VBM8 Software package. Difference of the gray matter structure was compared among the scalp acupuncture group, the control group, and the healthy volunteers.</p><p><b>RESULTS</b>Compared with healthy volunteers, gray matter injury of cerebral infarction patients mainly occurred in 14 brain regions such as cingulate gyrus, precuneus, cuneus, anterior central gyrus, insular lobe, and so on. They were mainly distributed in affected side. Two weeks after treatment when compared with healthy volunteers, gray matter injury of cerebral infarction patients in the scalp acupuncture group still existed in 8 brain regions such as bilateral lingual gyrus, posterior cingulate gyrus, left cuneus, right precuneus, and so on. New gray matter injury occurred in lingual gyrus and posterior cingulate gyrus. Two weeks after treatment when compared with healthy volunteers, gray matter injury of cerebral infarction patients in the control group existed in 23 brain regions: bilateral anterior cingulum, caudate nucleus, cuneate lobe, insular lobe, inferior frontal gyrus, medial frontal gyrus, precuneus, paracentral lobule, superior temporal gyrus, middle temporal gyrus, lingual gyrus, right postcentral gyrus, posterior cingulate gyrus, precentral gyrus, middle frontal gyrus, and so on. New gray matter injury still existed in 9 cerebral regions such as lingual gyrus, posterior cingulate gyrus, postcentral gyrus, and so on.</p><p><b>CONCLUSIONS</b>Brain gray matter structure is widely injured after cerebral infarction. Brain gray matter volume gradually decreased as time went by. Combined use of scalp acupuncture might inhibit the progression of gray matter injury more effectively.</p>

Acupuncture treatment modulates the resting-state functional connectivity of brain regions in migraine patients without aura / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the modulatory effect of acupuncture treatment on the resting-state functional connectivity of brain regions in migraine without aura (MWoA) patients.</p><p><b>METHODS</b>Twelve MWoA patients were treated with standard acupuncture treatment for 4 weeks. All MWoA patients received resting-state functional magnetic resonance imaging (fMRI) scanning before and after acupuncture treatment. Another 12 normal subjects matched in age and gender were recruited to serve as healthy controls. The changes of restingstate functional connectivity in MWoA patients before and after the acupuncture treatment and those with the healthy controls were compared.</p><p><b>RESULTS</b>Before acupuncture treatment, the MWoA patients had significantly decreased functional connectivity in certain brain regions within the frontal and temporal lobe when compared with the healthy controls. After acupuncture treatment, brain regions showing decreased functional connectivity revealed significant reduction in MWoA patients compared with before acupuncture treatment.</p><p><b>CONCLUSIONS</b>Acupuncture treatment could increase the functional connectivity of brain regions in the intrinsic decreased brain networks in MWoA patients. The results provided further insights into the interpretation of neural mechanisms of acupuncture treatment for migraine.</p>

Acupuncture treatment modulates the resting-state functional connectivity of brain regions in migraine patients without aura.

OBJECTIVE: To investigate the modulatory effect of acupuncture treatment on the resting-state functional connectivity of brain regions in migraine without aura (MWoA) patients. METHODS: Twelve MWoA patients were treated with standard acupuncture treatment for 4 weeks. All MWoA patients received resting-state functional magnetic resonance imaging (fMRI) scanning before and after acupuncture treatment. Another 12 normal subjects matched in age and gender were recruited to serve as healthy controls. The changes of restingstate functional connectivity in MWoA patients before and after the acupuncture treatment and those with the healthy controls were compared. RESULTS: Before acupuncture treatment, the MWoA patients had significantly decreased functional connectivity in certain brain regions within the frontal and temporal lobe when compared with the healthy controls. After acupuncture treatment, brain regions showing decreased functional connectivity revealed significant reduction in MWoA patients compared with before acupuncture treatment. CONCLUSIONS: Acupuncture treatment could increase the functional connectivity of brain regions in the intrinsic decreased brain networks in MWoA patients. The results provided further insights into the interpretation of neural mechanisms of acupuncture treatment for migraine.

Correlations between cholinesterase activity and cognitive scores in post-ischemic rats and patients with vascular dementia.

The biochemical changes such as the activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were investigated in rats with global cerebral ischemia and in vascular dementia (VaD) subjects in this study. The AChE activity showed a significant decrease in plasma and a significant increase in the hippocampus but not in the cerebral cortices in the post-ischemic rats as compared to the controls. The learning abilities and spatial memory were impaired in the post-ischemic rats as compared to controls. Furthermore, the AChE activity in plasma was significantly reduced in VaD subjects as compared to normal control subjects. The BuChE activity did not show any change in both post-ischemic rats and VaD patients. Interestingly, the decreased AChE activity in plasma from the post-ischemic rats and the VaD subjects showed a significant correlation with the declined learning and memory ability, and the Mini-Mental State Examination score, respectively. These data suggest that the AChE activity is involved in the cognitive recovery after ischemia, and the plasma level of AChE might be a reliable supplementary peripheral biomarker to evaluate the cognitive recovery degree of VaD patients.