Pyroptosis is the programmed death of cells accompanied by an inflammatory response and is widely involved in the development of a variety of diseases, such as infectious diseases, cardiovascular diseases, and neurodegeneration. It has been shown that cellular scorching is involved in the pathogenesis of pulmonary arterial hypertension ( PAH) in cardiovascular diseases. Patients with PAH have perivascular inflammatory infiltrates in lungs, pulmonary vasculopathy exists in an extremely inflam-matory microenvironment, and pro-inflammatory factors in cellular scorching drive pulmonary vascular remodelling in PAH patients. This article reviews the role of cellular scorch in the pathogenesis of PAH and the related research on drugs for the treatment of PAH, with the aim of providing new ideas for clinical treatment of PAH.

Obiective Alzheimer’s disease (AD) is a degenerative disease of the central nervous system (CNS) caused by a variety of risk factors. There are various pathological changes, but apoptosis of the neurological meridian cells is one of the most important pathological bases. Hyperlipidemia is a high-risk factor for the development of AD, which can lead to increased levels of oxidized low-density lipoprotein (ox-LDL) in brain tissues. PCSK9 is a protease closely related to lipid metabolism, but studies have shown that it may be related to the development of AD. LRP1 is abundantly expressed in neuronal cells, and it is an important transporter for the clearance of Aβ. There is now a large amount of literature confirming that PCSK9 can induce the degradation of LRP1. PI3K/AKT is an important signaling pathway in vivo, which plays an important role in apoptosis, and there is now a large amount of literature confirming that LRP1 activates the PI3K/AKT pathway, which has an anti-apoptotic effect. So can PCSK9 affect the PI3K/AKT pathway through LRP1 and thus regulate neuronal apoptosis? This deserves further investigation.The aim of this study was to explore the role of PCSK9 in mediating ox-LDL pro-apoptotic neuronal cell death and its mechanism, and then further elaborate the mechanism of hyperlipidemia leading to neurodegenerative diseases such as AD. MethodsFirstly, PC12 cells were treated with different concentrations of ox-LDL (0, 25, 50, 75 and 100 mg/L) for 24 h. Oil red O staining was used to detect lipid accumulation in PC12 cells, Hoechst33258 staining and flow cytometry to detect apoptosis in PC12 cells, ELISA to detect the content of Aβ secreted by PC12, Western blot to detect expression of SREBP2, PCSK9 and LRP1. Then PC12 cells were treated with 75 mg/L ox-LDL for different times (0, 6, 12, 24, 48 h), and Western blot were performed to detect the expression of SREBP2, PCSK9 and LRP1. Finally, after transfecting 100 nmol/L PCSK9 siRNA into PC12 cells for 48 h, PC12 cells were treated with 75 mg/L ox-LDL for 24 h, Hoechst33258 staining and flow cytometry to detect apoptosis rate of PC12 cells, and Western blot to detect PCSK9, LRP1, PI3K, AKT, P-PI3K , P-AKT, NF-κB, Bcl-2, Bax, Caspase-9 and Caspase-3 expression, and ELISA detected Aβ content secreted by PC12 cells. Resultsox-LDL increased lipid accumulation and promoted apoptosis and Aβ secretion in PC12 cells, as well as increasing the expression of SREBP2 and PCSK9 and decreasing the expression of LRP1 in PC12 cells. pCsk9 siRNA could be inhibited through the PI3K/AKT pathway and the NF-κB-Bcl-2/Bax-Caspase-9/3 pathway to inhibit ox-LDL-induced apoptosis in PC12 cells while increasing Aβ secretion in PC12 cells. Conclusionox-LDL plays a bidirectional regulatory role in ox-LDL-induced apoptosis of PC12 cells by inducing an increase in PCSK9 expression and a decrease in LRP1 expression in PC12 cells, which in turn affects different signaling pathways downstream.

Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.

Panax notoginseng is the dried root and rhizome of Panax notoginseng(Burk.)F.H.Chen,a perennial erect herb of the genus Ginseng of the family Wujiaceae.As a traditional Chinese medicine in our country,Panax notoginseng has a good tonic effect,and the Dictionary of Traditional Chinese Medicines has the words that Panax notoginseng is used to tonify the blood,remove the blood stasis and damage,and stop epistaxis.It can also be used to pass the blood and tonify the blood with the best efficacy,and it is the most precious one of the prescription med-icines.Eaten raw,it removes blood stasis and generates new blood,subdues swelling and stabilizes pain,stops bleeding with-out leaving stasis,and promotes blood circulation without hurting the new blood;taken cooked,it can be used to replenish and strengthen the body.Notoginsenoside R1 is a characteristic com-pound in the total saponin of Panax ginseng.In recent years,China's aging has been increasing,and the incidence of neuro-logical disorders has been increasing year by year.Meanwhile,reports on notoginsenoside R1 in the treatment of neurological disorders are increasing,and its neuroprotective effects have been exerted with precise efficacy.The purpose of this paper is to review the treatment of neurological diseases and the mecha-nism of action of notoginsenoside R1,so as to provide a certain theoretical basis for clinical use and new drug development.

Aim To investigate the effeet of Eehinaeo- side ( ECH ) regulating the expression of prohibitin (PHB) on MPP+ -induced apoptosis of SH-SY5Y eells and the underlying mechanism.Methods SH-SY5Y eells were seleeted and divided into control group, MPP+ group, MPP+ + ECH group, NC + MPP + group, NC + MPP+ + ECH group, PHB-RNAi + MPP + + ECH group.Cell survival rate was determined by CCK-8 assay.Cell morphology was observed using an inverted phase contrast mieroscope; the apoptotie eells were observed by Hoechst33342 fluorescence staining, whereas apoptotie rate, reactive oxygen speeies eon- tent, and mitochondrial membrane potential were ana¬lyzed by flow eytometry.The relative protein expres¬sions of PHB, Akt, p-Akt, Bel-2, Bax, and cleaved- easpase3 were determined by Western blot.Results Compared with eontrol group, the eell survival rate of MPP+ group signifieantly deereased.The growth state of the eells beeame significantly worse.Intracellular ROS content inereased, mitoehondrial membrane po tential decreased, apoptosis-related protein expression increased and the apoptotic rate increased.Compared with MPP+ group, MPP+ + ECH group significantly increased cell viability.The growth status of cells was significantly improved.Intracellular ROS content de¬creased, mitochondrial membrane potential increased, apoptosis-related protein expression decreased, and the apoptotic rate decreased significantly.The expression levels of PHB and p-Akt significantly increased.Com¬pared with NC + MPP+ + ECH group, p-Akt level de¬creased and the cell apoptotic rate increased in PHB- RNAi +MPP+ + ECH group.Conclusions Echino- side can reduce MPP + - induced apoptosis of SH-SY5Y cells, which may be realized by upregulating PHB ex¬pression and phosphorylation of Akt to protect mito¬chondrial function.

With the development of social economy and improvement of people's health condition， life expectancy continues to extend and people are more concerned about the quality of life. Nowadays people's attention has shifted from living longer lives to living healthier lives. Life expectancy can only reflect the length of life， but not the health condition and quality of life. Meanwhile， healthy life expectancy contains death and disability information， which comprehensively reflects the length and quality of life and evaluates the health status of the population comprehensively. Through literature search and review， the article summarized the research on healthy life expectancy in recent years， including the concept proposal， index development， calculation， and application progress of health life expectancy. The research methods of healthy life expectancy are summarized in order to provide academic reference for further research.

Apoptosis ; B7-H1 Antigen/genetics* ; Carcinoma, Non-Small-Cell Lung/genetics* ; Cost-Benefit Analysis ; Humans ; Immune Checkpoint Inhibitors ; Immunotherapy ; Ligands ; Lung Neoplasms/genetics*

Objective: To predict B cell and T cell epitopes of 22-kDa, 47-kDa, 56-kDa and 58-kDa proteins. Methods: The sequences of 22-kDa, 47-kDa, 56-kDa and 58-kDa proteins which were derived from Orientia tsutsugamushi were analyzed by SOPMA, DNAstar, Bcepred, ABCpred, NetMHC, NetMHC II and IEDB. The 58-kDa tertiary structure model was built by MODELLER9.17. Results: The 22-kDa B-cell epitopes were located at positions 194-200, 20-26 and 143-154, whereas the T-cell epitopes were located at positions 154-174, 95-107, 17-25 and 57-65. The 47-kDa protein B-cell epitopes were at positions 413-434, 150-161 and 283-322, whereas the T-cell epitopes were located at positions 129-147, 259-267, 412-420 and 80-88. The 56-kDa protein B-cell epitopes were at positions 167-173, 410-419 and 101-108, whereas the T-cell epitopes were located at positions 88-104, 429-439, 232-240 and 194-202. The 58-kDa protein B-cell epitopes were at positions 312-317, 540-548 and 35-55, whereas the T-cell epitopes were located at positions 415-434, 66-84 and 214-230. Conclusions: We identified candidate epitopes of 22-kDa, 47-kDa, 56-kDa and 58-kDa proteins from Orientia tsutsugamushi. In the case of 58-kDa, the dominant antigen is displayed on tertiary structure by homology modeling. Our findings will help target additional recombinant antigens with strong specificity, high sensitivity, and stable expression and will aid in their isolation and purification.

Objective At present, there are few reports about the relationship between Chemerin and the occurrence and development of breast cancer. The aim of this study is to investigate Chemerin expression in breast cancer mice and its effect on proliferation and migration of breast cancer cells. Methods 30 Balb/c mice were randomly divided into two groups (Normal mice 15, Tumor-bearing mice 15). The 4T1 breast cancer cells were inoculated to construct breast cancer mice model. The expressions of Chemerin in peripheral blood and breast cancer tissue were detected by ELISA and Western blot, respectively. The relationship between Chemerin expression and breast cancer was analyzed. Breast cancer cells MCF-7 and MDA-MB-231 were treated with different concentrations of recombinant Chemerin protein and Chemerin neutralizing antibody. Three groups were set up in the experiment, including control group (1640 or DMEM culture medium, no cells), recombinant Chemerin protein group (100 μg/L, no dilution by serum-free medium) and Chemerin neutralizing antibody group (100 μg/L, no dilution by serum-free medium). The effects of Chemerin on cell proliferation and migration were detected by MTT assay and wound healing assay respectively. Results The expressions of Chemerin in peripheral blood and mammary gland of tumor bearing mice were significantly higher than that in normal mice (both P<0.05). The scratch mobility and MTT absorbance (OD) values of breast cancer cells treated with recombinant chemerin protein increased significantly with the increase of protein concentration (P<0.05).However, they significantly decreased after cells treated with chemerin neutralizing antibody (P<0.05). Conclusion Chemerin could promote the proliferation and migration of breast cancer cells in a concentration-dependent manner, thereby promotinge the occurrence and development of breast cancer.

Nephronectin (NPNT) is a novel extracellular matrix protein and a new ligand of integrin α8β1. Recent studies showed that NPNT is highly expressed in kidney, lung, thyroid, etc, and it may play an important role in many pathological conditions. NPNT is involved in the process of kidney development and acute kidney injury, regulates proliferation and differentiation of osteoblast, and induces the vasculogenesis in vitro. NPNT may play a key role in pathological osteoporosis and therefore be a new therapeutic target of bone diseases. NPNT gene variants are not only associated with lung function, but also potentially implicated in chronic airway diseases development. Moreover, NPNT is also an important factor that mediates pathology of cardiac, epidermis, breast, liver and teeth diseases. In this paper, we reviewed some research progresses on the structure, distribution, physiological and pathophysiological functions of NPNT.
Cell Differentiation ; Cell Proliferation ; Extracellular Matrix Proteins ; physiology ; Humans ; Kidney ; physiology ; Osteoblasts ; cytology ; Osteoporosis