Triggering receptor expressed on myeloid cells 2 (TREM2)-mediated microglial phagocytosis is an energy-intensive process that plays a crucial role in amyloid beta (Aβ) clearance in Alzheimer's disease (AD). Energy metabolic reprogramming (EMR) in microglia induced by TREM2 presents therapeutic targets for cognitive impairment in AD. Jiawei Xionggui Decoction (JWXG) has demonstrated effectiveness in enhancing energy supply, protecting microglia, and mitigating cognitive impairment in APP/PS1 mice. However, the mechanism by which JWXG enhances Aβ phagocytosis through TREM2-mediated EMR in microglia remains unclear. This study investigates how JWXG facilitates microglial phagocytosis and alleviates cognitive deficits in AD through TREM2-mediated EMR. Microglial phagocytosis was evaluated through immunofluorescence staining in vitro and in vivo. The EMR level of microglia was assessed using high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA) kits. The TREM2/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway was analyzed using Western blotting in BV₂ cells. TREM2^-/- BV₂ cells were utilized for reverse validation experiments. The Aβ burden, neuropathological features, and cognitive ability in APP/PS1 mice were evaluated using ELISA kits, immunohistochemistry (IHC), and the Morris water maze (MWM) test. JWXG enhanced both the phagocytosis of EMR disorder-BV₂ cells (EMRD-BV₂) and increased EMR levels. Notably, these effects were significantly reversed in TREM2^-/- BV₂ cells. JWXG elevated TREM2 expression, adenosine triphosphate (ATP) levels, and microglial phagocytosis in APP/PS1 mice. Additionally, JWXG reduced Aβ-burden, neuropathological lesions, and cognitive deficits in APP/PS1 mice. In conclusion, JWXG promoted TREM2-induced EMR and enhanced microglial phagocytosis, thereby reducing Aβ deposition, improving neuropathological lesions, and alleviating cognitive deficits.
Drugs, Chinese Herbal/pharmacology* ; Microglia/drug effects* ; Phagocytosis ; Cognitive Dysfunction/drug therapy* ; Metabolic Reprogramming ; Animals ; Mice ; Cell Line ; Receptors, Immunologic/metabolism* ; Membrane Glycoproteins/metabolism* ; Signal Transduction ; Amyloid beta-Peptides/metabolism* ; Energy Metabolism

Objective To explore the effect of Mycobacterium tuberculosis infection on the primary cilia of mono-cytse-macrophages and its potential mechanisms of promoting osteoclast differentiation.Methods Bone marrow-de-rived mononuclear cells(BMMCs)isolated from patients in control group and spinal tuberculosis group(TB group)were performed in vitro culture,and then cultured with Mycobacterium tuberculosis,infection model(Rv group)was constructed.Changes in cilia were observed by fluorescence staining and scanning electron microscopy tech-nique,a mouse spinal TB model was constructed for validating.Results Compared with the control group,the ex-pression of primary cili markers in the lesion of bone tissue of patients in TB group decreased significantly;After co-culturing with Mycobacterium tuberculosis,the ratio(48.56％±7.77％vs 9.58％±5.59％)and length(4.050[3.289,4.666]μm vs 0[0,0.676]μm)of primary cilia of monocytes-macrophages in the Rv group decreased sig-nificantly;The infiltration of osteoclasts in the bone marrow cavity of spinal TB mice was obvious,and the propor-tion and length of primary cilia decreased significantly.Conclusion Intracellular infection of Mycobacterium tuberculosis can induce degradation of primary cilia in monocytes-macrophages,promote osteoclast differentiation,and exacerbate vertebral bone resorption.

Objective By observing the effect of angiotensin Ⅱ in the locus coeruleus of the brain on high salt intake and the impact of losartan on this effect,this study explores effective implementation methods for salt restriction strategies.Methods Brain catheterization and microinjection were used to administer single microinjection of Ang Ⅱ into the locus coeruleus of rats,as well as combined microinjection of saline,Ang Ⅱ,and angiotensin Ⅱ type 1 receptor,AT1R antagonist losartan was used to observe the changes in the intake and water intake of hypertonic sodium chloride solution in rats with different sodium intake models;Single microinjection of Ang Ⅱ into the locus coeruleus of rats was performed to observe changes in water intake in water deprived rats,as well as changes in urine output,sodium excretion,horizontal and vertical activity in normal rats.Results Whether in rats treated with"water deprivation partial rehydration(WD-PR)"or in rats treated with"subcutaneous combined injection of furosemide(FURO)and Captopril(CAP)(FURO-CAP)",microinjection of 0.1 ng,1 ng,and 10 ng doses of Ang Ⅱ into the locus coeruleus caused a dose-dependent increase in 0.3 mol/L NaCl intake and water intake.However,pre injection of AT1R antagonist losartan at doses of 0.5 μ g,5 μ g,and 50 μ g significantly inhibited the injection of 10 ng Ang Ⅱ into the same site in a dose-dependent manner.The increase in intake of 0.3 mol/L NaCl and water caused by it.Compared with injection of saline into the locus coeruleus,injection of 10.0ng dose of Ang Ⅱ into the locus coeruleus significantly increased the horizontal and vertical activity of rats,but had no significant effect on renal excretion.Conclusion Losartan can inhibit the high salt intake induced by Ang Ⅱ in the locus coeruleus of the brain,and can be used as an effective drug in the salt limiting strategy for controlling hypertension.

Objective By observing the effect of angiotensin Ⅱ in the locus coeruleus of the brain on high salt intake and the impact of losartan on this effect,this study explores effective implementation methods for salt restriction strategies.Methods Brain catheterization and microinjection were used to administer single microinjection of Ang Ⅱ into the locus coeruleus of rats,as well as combined microinjection of saline,Ang Ⅱ,and angiotensin Ⅱ type 1 receptor,AT1R antagonist losartan was used to observe the changes in the intake and water intake of hypertonic sodium chloride solution in rats with different sodium intake models;Single microinjection of Ang Ⅱ into the locus coeruleus of rats was performed to observe changes in water intake in water deprived rats,as well as changes in urine output,sodium excretion,horizontal and vertical activity in normal rats.Results Whether in rats treated with"water deprivation partial rehydration(WD-PR)"or in rats treated with"subcutaneous combined injection of furosemide(FURO)and Captopril(CAP)(FURO-CAP)",microinjection of 0.1 ng,1 ng,and 10 ng doses of Ang Ⅱ into the locus coeruleus caused a dose-dependent increase in 0.3 mol/L NaCl intake and water intake.However,pre injection of AT1R antagonist losartan at doses of 0.5 μ g,5 μ g,and 50 μ g significantly inhibited the injection of 10 ng Ang Ⅱ into the same site in a dose-dependent manner.The increase in intake of 0.3 mol/L NaCl and water caused by it.Compared with injection of saline into the locus coeruleus,injection of 10.0ng dose of Ang Ⅱ into the locus coeruleus significantly increased the horizontal and vertical activity of rats,but had no significant effect on renal excretion.Conclusion Losartan can inhibit the high salt intake induced by Ang Ⅱ in the locus coeruleus of the brain,and can be used as an effective drug in the salt limiting strategy for controlling hypertension.

Objective To explore the effect of Mycobacterium tuberculosis infection on the primary cilia of mono-cytse-macrophages and its potential mechanisms of promoting osteoclast differentiation.Methods Bone marrow-de-rived mononuclear cells(BMMCs)isolated from patients in control group and spinal tuberculosis group(TB group)were performed in vitro culture,and then cultured with Mycobacterium tuberculosis,infection model(Rv group)was constructed.Changes in cilia were observed by fluorescence staining and scanning electron microscopy tech-nique,a mouse spinal TB model was constructed for validating.Results Compared with the control group,the ex-pression of primary cili markers in the lesion of bone tissue of patients in TB group decreased significantly;After co-culturing with Mycobacterium tuberculosis,the ratio(48.56％±7.77％vs 9.58％±5.59％)and length(4.050[3.289,4.666]μm vs 0[0,0.676]μm)of primary cilia of monocytes-macrophages in the Rv group decreased sig-nificantly;The infiltration of osteoclasts in the bone marrow cavity of spinal TB mice was obvious,and the propor-tion and length of primary cilia decreased significantly.Conclusion Intracellular infection of Mycobacterium tuberculosis can induce degradation of primary cilia in monocytes-macrophages,promote osteoclast differentiation,and exacerbate vertebral bone resorption.

Glioblastoma multiforme (GBM), a highly malignant and heterogeneous brain tumor, contains various types of tumor and non-tumor cells. Whether GBM cells can trans-differentiate into non-neural cell types, including mural cells or endothelial cells (ECs), to support tumor growth and invasion remains controversial. Here we generated two genetic GBM models de novo in immunocompetent mouse brains, mimicking essential pathological and molecular features of human GBMs. Lineage-tracing and transplantation studies demonstrated that, although blood vessels in GBM brains underwent drastic remodeling, evidence of trans-differentiation of GBM cells into vascular cells was barely detected. Intriguingly, GBM cells could promiscuously express markers for mural cells during gliomagenesis. Furthermore, single-cell RNA sequencing showed that patterns of copy number variations (CNVs) of mural cells and ECs were distinct from those of GBM cells, indicating discrete origins of GBM cells and vascular components. Importantly, single-cell CNV analysis of human GBM specimens also suggested that GBM cells and vascular cells are likely separate lineages. Rather than expansion owing to trans-differentiation, vascular cell expanded by proliferation during tumorigenesis. Therefore, cross-lineage trans-differentiation of GBM cells is very unlikely to occur during gliomagenesis. Our findings advance understanding of cell lineage dynamics during gliomagenesis, and have implications for targeted treatment of GBMs.
Mice ; Animals ; Humans ; Glioblastoma/pathology* ; Endothelial Cells/pathology* ; DNA Copy Number Variations ; Brain/metabolism* ; Brain Neoplasms/pathology*

Blood Coagulation Disorders ; physiopathology ; Blood Pressure ; physiology ; Hemodynamics ; physiology ; Humans ; Orthostatic Intolerance ; physiopathology ; Platelet Count ; Posture ; physiology

Objective To measure the change of facial volume maintenance rate after autologous fat grafted for repaired progressive facial hemiatrophy by using three-dimensional digital technology.Methods 3D scanner was used to acquire facial data in 10 patients with progressive facial hemiatrophy before operation;Mimics 17.0 software was used to reconstruce patients' facial 3D model and to calculate the volume of facial tissue defect;autologous fat was grafted to repair facial deformity.The facial volume maintenance rate was calculated in all the patients 3 months and 6 months after operation.Results We had performed facial 3D data acquisition and facial repaired with autologus fat grafted in 10 patients;patients' facial morphology was improved.The mean facial volume maintenance rate was (35.80±3.44)％ in 3 months and (27.82±3.80)％ 6 months after surgery.Conclusions The mean facial volume maintenance rate in postoperative 3 months is inferior to that in 6 months in single autologous fat grafted for repairing progressive facial hemiatrophy.

Objective:To investigate the effect of continuous use of aspirin on gallbladder function and thromboembolism risk in the patients undergoing laparoscopic cholecystectomy. Methods:Totally 100 patients undergoing laparoscopic cholecystectomy from October 2010 to October 2014 were selected as the subjects. All the patients were given aspirin for a long time and randomly divided into two groups. The patients in the observation group were treated with aspirin continuously, and the control group suspended aspirin 7 days before the surgery and administrated aspirin continuously after the surgery. The perioperative thromboembolism,changes in gallbladder function and coagulation function, and intraoperative and postoperative differences in the indicators were compared between the groups. Results:The gallbladder volume in the observation group decreased, and the gallbladder contraction rate and emptying index were higher than those on the 7th day before the surgery(P < 0.05). The above indices were significantly better than those in the control group (P < 0.05). There was no significant change in the coagulation function after the treatment in both groups(P >0.05). There were no significant differences in the operative time,intraoperative blood loss, postoperative drainage and postoperative hospital stay between the groups (P > 0.05). The total incidence of perioperative thromboembolism in the observation group was 2.0%,which was significantly lower than that in the control group(P< 0.05).Conclusion:Continuous use of aspirin during laparoscopic cholecystectomy is beneficial to reducing the volume of gallbladder, promoting gallbladder emptying and reducing the risk of perioperative thromboembolism. The reasonable use has no obvious effect on the postoperative coagulation function.