Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

Parkinson's disease(PD)is a common neurodegenerative disease with a complex pathogenesis,and a large number of studies have shown that mitochondrial dysfunction is an important causative factor for PD,whereas dysregulation of mitochondrial quality control is a key factor leading to mitochondrial dysfunction,and that aberrant mitochondrial biogenesis,fusion/fission imbalance,and mitochondrial hyperautophagy are closely associated with the onset of PD,but the role of the mitochondrial quality control system in the progression of PD is unclear.Therefore,this paper reviews the mechanism of mitochondrial quality control system in PD,with the aim of providing new ideas and theoretical basis for the clinical prevention and treatment of PD.

PD is a neurodegenerative disease characterized by degenerative death of dopaminergic neurons in the substantia nigra,exhibiting a range of motor and non-motor symptoms with serious effects on quality of life.circRNA is a covalently closed-loop non-coding RNA that plays a major role in PD progression.This article reviews the involvement of circRNA in oxidative stress,regulation of transcription,neuroinflammation,autophagy,and α-synuclein.

Objective To explore the effect of the nursing intervention for Internet+whole course breastfeeding support based on lactation physiology on exclusive breastfeeding of cesarean section women.Methods Using the convenience sampling method,198 women who were from prenatal examination to delivery in the Obstetrical Department of a tertiary hospital in Nanning city from July 2022 to February 2023 were selected,with 99 women in each group.The experimental group adopted the nursing intervention for Internet+whole course breastfeeding support based on lactation physiology,while the control group adopted routine nursing care.The rates of exclusive breastfeeding within 6 months,breastfeeding or milking frequency within 3 days postpartum,incidence of nipple pain,breastfeeding knowledge scores,and breastfeeding self-efficacy scores were compared between the 2 groups.Results No shedding occurred in both groups.The exclusive breastfeeding rates in the experimental group at postpartum 3 days,14 days,42 days,4 months,and 6 months were higher than that in the control group.The comparison of the rates of exclusive breastfeeding between 2 groups at different time points showed that the intergroup effect,time effect and interaction effect were statistically significant(P＜0.05).The 2 groups were stratified by maternal and child separation,and the rates of exclusive breastfeeding of the experimental group at postpartum 42 days,4 months and 6 months were higher than that of the control group(P＜0.05).The frequency of breastfeeding or milking within 3 days postpartum,incidence of nipple pain,breastfeeding knowledge scores,and breastfeeding self-efficacy scores were higher in the experimental group than those in the control group(P＜0.05).Conclusion The nursing intervention for Internet+whole course breastfeeding support based on lactation physiology can improve the compliance of lactation behavior in cesarean section women and promote the establishment of lactation,which can significantly improve the rate of exclusive breastfeeding within 6 months.

Objective:To investigate the correlation of serum testosterone level with severity and characteristics of coronary plaque, stent implantation rate and major cardiovascular adverse events(MACE)in elderly male patients with coronary heart disease(CHD).Methods:In this retrospective study, a total of 63 elderly male patients of the Third People's Hospital of Hangzhou with coronary angiography(CAG)-confirmed CHD and to undergo percutaneous coronary intervention(PCI)were selected.According to serum testosterone level, they were divided into the low testosterone(low T)group and the normal testosterone(normal T)group.Optical coherence tomography(OCT)was performed in both groups to define the characteristics of coronary artery lesions and guide stent implantation.The correlation of serum testosterone level with blood lipids, glycated hemoglobin(HbA1c), degree of coronary artery lesions, plaque characteristics, stent implantation and MACE in two groups were analyzed.The in-stent restenosis rate after stent implantation and the variation of minimum lumen diameter of stent were determined during 12 months follow up in both groups.Results:Total cholesterol(TC), low-density lipoprotein(LDL-C)and HbA1c were higher in the low T group than in the normal T group( t=7.808、-5.871、6.611, all P<0.05). When taking testosterone as the independent variable, and TC, triglycerides(TG), LDL-C, high density lipoprotein cholesterol(HDL-C)and HbA1c as the dependent variables, linear regression analysis showed that TC, LDL-C and HbA1c were negatively correlated with testosterone level( β=-0.733, -0.716, -0.581, P<0.05). More than 2 vascular lesions were more common in low testosterone group versus the control group( χ2=8.66, P<0.05). Mixed plaques, lipid plaques, and calcified plaques were more commonly found in low testosterone group versus the control group( χ2=7.87, P<0.05). Unstable plaques were more common in the low T group( χ2=6.14, P<0.05). The low T group vs the normal T group, coronary stent implantation rate were 93.3%(28/30 cases) vs.66.7%(22/33 cases), the difference was statistically significant( χ2=6.82, P<0.05). When testosterone, TC, TG, LDL-C, HDL-C, HbA1c were taken as the independent variables, and the stent implantation rate was the dependent variable, logistic regression analysis results showed that only testosterone, TC and HbA1c were independently correlated with stent implantation rate( OR=0.971、425.523、0.004, P<0.05). There was no statistically significant difference in minimum stent lumen diameters between the two groups under OCT-guided coronary stent implantation( t=-1.064, P>0.05). During 12 months follow up, the MACE0 incidence was 26.7%(8/30 cases, in low T group)than 6.1%(2/33 cases, in normal T group), with statistically significant difference( χ2=5.00, P<0.05). When taking testosterone, TC, TG, LDL-C, HDL-C and HbA1c as the independent variables, and MACE as the dependent variable, logistic regression analysis results showed that only testosterone and LDL-C were independently correlated with MACE( OR=0.968, 0.008, P<0.05). Conclusions:Serum testosterone level is negatively correlated with TC, LDL-C and HbA1c, and may be correlated with the degree of coronary artery lesions, plaque properties, MACE and stent implantation rate of CHD patients.Serum testosterone can be used to evaluate the characteristics and conditions of CHD, and help to predict the prognosis of CHD.The OCT is a good guide tool for coronary stent implantation.

Chronic heart failure(CHF) is the end stage of various cardiovascular diseases and is one of the common diseases among the elderly in China. Sarcopenia is a geriatric syndrome characterized by the age-related loss of skeletal muscle quantity and/or mass and the decline in muscle strength and/or physical performance. There is a common pathophysiological mechanism of CHF and sarcopenia, and they interact with each other and influence each other′s prognosis. There are few confirmed effective treatments for sarcopenia, and even fewer measures that can help slow the progression of both syndromes. However, on the basis of heart failure treatment hormone therapy, exercise training and nutritional support may slow the progression of sacopenia. This article reviews the recent advances in the relationship between elderly CHF patients with sarcopenia and related treatment.

Objective To evaluate the anti-inflammatory effects of LCA, which is the active component from Litsea cubeba (Lour.) Pers. Methods Pharmacodynamic evaluations of ear swelling and cotton ball granuloma models were used in animal experiments. In vitro experiment, lipopolysaccharide (LPS) stimulated monocyte macrophage RAW264.7 cells were used to evaluate the anti-inflammatory activity of LCA by detecting the secretions of nitric oxide (NO), tumor necrosis factor-α (TNF-α), the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein. Results In ear swelling experiment, the extent of ear swelling was significantly lower in the LCA treated group than the model group. The inhibition rate was greater in the high LCA concentration group than the positive drug group. In addition, LCA reduced the weight of cotton ball granuloma markedly. At the cell level, LCA significantly inhibited the secretions of NO, TNF-α and reduced the expressions of iNOS and COX-2 in LPS-stimulated RAW 264.7 cells. Conclusion LCA has significant anti-inflammatory effects in vitro and in vivo. The further studies are warranted for the development of anti-inflammatory drugs.

Objective To study the effects of the different concentrations of ethanol extracts of Smilax China on ear edema in mice and granuloma in rats,and to provide an evidence for optimizing the extraction process. Methods Effects of different concentrations of ethanol extracts of Smilax China on the xylene-induced ear edema in mice and the cotton ball-induced granuloma hyperplasia in rats were tested . Results Compared with the model controls,70% ethanol extracts of Smilax China at high,medium and low doses significantly inhibited ear edema in mice (t=2. 58,P<0. 05;t=2. 28,P<0. 05;t=2. 17,P<0. 05) and reduced the granuloma hyperplasia in rats(t=5. 28,P<0. 01;t=5. 24,P<0. 01;t=5. 17,P<0. 01). Conclusion The 70% ethanol extracts of Smilax China at three doses present the most active antiinflammatory effect,confirmed in both mice ear edema and rats granuloma models.

OBJECTIVETo determine the effective fraction of Smilax for treatment of chronic pelvic inflammatory disease (CPID) by pharmacodynamic screening as the basis for further development of sarsaparilla preparations.

METHODSThe chemical fractions of Smilax were administered intragastrically in rat models of CPID induced by injecting phenol mucilage into the uterus to observe the therapeutic effects. The anti-inflammatory effects of different extract fractions from Smilax were tested in mice with xylene-induced ear edema and in rats with cotton-ball-induced granuloma.

RESULTSHigh-dose ethyl acetate extract of Smilax could obviously inhibit uterus inflammation in rats with CPID, showing also strong anti-inflammatory effects against ear edema in mice and granuloma in rats (P<0.01). The moderate dose of ethyl acetate extract also obviously ameliorated the inflammation. Both the ethyl acetate extract fraction and the total extract fraction of Smilax showed anti-inflammatory effects, while the former produced strong effects while the latter has only weak actions.

CONCLUSIONThe ethyl acetate extract fraction of Smilax is the effective fraction to produce anti-inflammatory and anti-CPID effects.

Animals ; Anti-Inflammatory Agents ; therapeutic use ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Mice ; Mice, Inbred Strains ; Pelvic Inflammatory Disease ; drug therapy ; Rats ; Rats, Sprague-Dawley ; Smilax