1.Functions of Dynamin and Its Family Proteins
Zi-Yan YANG ; Zhao-Hong JIANG ; Qian-Yi ZHOU ; Zhi-Ming CHEN
Progress in Biochemistry and Biophysics 2024;51(11):2821-2831
The dynamin superfamily protein (DSP) encompasses a group of large GTPases that are involved in various membrane remodeling processes within the cell. These proteins are characterized by their ability to hydrolyze GTP, which provides the energy necessary for their function in membrane fission, fusion, and tubulation activities. Dynamin superfamily proteins play critical roles in cellular processes such as endocytosis, organelle division, and vesicle trafficking. It is typically classified into classical dynamins and dynamin-related proteins (Drp), which have distinct roles and structural features. Understanding these proteins is crucial for comprehending their functions in cellular processes, particularly in membrane dynamics and organelle maintenance. Classical dynamins are primarily involved in clathrin-mediated endocytosis (CME), a process crucial for the internalization of receptors and other membrane components from the cell surface into the cell. These proteins are best known for their role in pinching off vesicles from the plasma membrane. Structually, classical dynamins are composed of a GTPase domain, a middle domain, a pleckstrin homology (PH) domain that binds phosphoinositides, a GTPase effector domain (GED), and a proline-rich domain (PRD) that interacts with SH3 domain-containing proteins. Functionally, the classical dynamins wrap around the neck of budding vesicles, using GTP hydrolysis to constrict and eventually acting as a “membrane scissor” to cut the vesicle from the membrane. In mammals, there are three major isoforms: dynamin 1 (predominantly expressed in neurons), dynamin 2 (ubiquitously expressed), and dynamin 3 (expressed in testes, lungs, and neurons). Recent studies have also revealed some non-classical functions of classical dynamins, such as regulating the initiation and stabilization of clathrin-coated pits (CCPs) at the early stages of CME, influencing the formation of the actin cytoskeleton and cell division. Drps share structural similarities with classical dynamins but are involved in a variety of different cellular processes, primarily related to the maintenance and remodeling of organelles, and can be mainly categorized into “mediating membrane fission”, “mediating membrane fusion” and “non-membrane-dependent functions”. Proteins like Drp1 are crucial for mitochondrial division, while others like Fis1, Mfn1, and Mfn2 are involved in mitochondrial and peroxisomal fission and fusion processes, which are essential for the maintenance of mitochondrial and peroxisomal integrity and affect energy production and apoptosis. Proteins like the Mx protein family exhibit antiviral properties by interfering with viral replication or assembly, which is critical for the innate immune response to viral infections. Some other proteins are involved in the formation of tubular structures from membranes, which is crucial for the maintenance of organelle morphology, particularly in the endoplasmic reticulum and Golgi apparatus. Studies on dynamin superfamily proteins have been extensive and have significantly advanced our understanding of cellular biology, disease mechanisms, and therapeutic potential. These studies encompass a broad range of disciplines, including molecular biology, biochemistry, cell biology, genetics, and pharmacology. By comprehensively summarizing and organizing the structural features and functions of various members of the dynamin superfamily protein, this review not only deepens the understanding of its molecular mechanisms, but also provides valuable insights for clinical drug research related to human diseases, potentially driving further advancements in the field.
2.Studies on the chemical composition of Ferula feruloides
Ying-he BI ; Ke-jian PANG ; Hui-zi LI ; Yerlan BAHETJAN ; Muguli MUHAXI ; Yan HU ; Xin-zhou YANG
Acta Pharmaceutica Sinica 2024;59(7):2069-2076
Eleven compounds were isolated and purified from the ethyl acetate part of 80% ethanol extract of
3.Secondary metabolites from endophytic fungi Candida sp.of Berberis atrocarpa
Ming-Zhuo GUO ; Shu-Fang MA ; Shi-Miao WANG ; Ya-Ping FENG ; Yan OUYANG ; Ke-Jian PANG ; Zi-Wei JIAO ; Xin-Zhou YANG
Chinese Traditional Patent Medicine 2024;46(9):3000-3005
AIM To study the secondary metabolites from the endophytic fungi Candida sp.of Berberis atrocarpa Schneid.METHODS The ethyl acetate fraction and petroleum ether fraction from the secondary metabolites of Candida sp.fermentation extract were separated and purified by silica gel,Sephadex LH-20 and preparative liquid chromatography,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Eighteen compounds were isolated and identified as 1-phenyl-1,2-ethanediol(1),4-hydroxyphenethyl alcohol(2),4-hydroxybenzoic acid(3),4-hydroxyphenylacetic acid(4),3-hydroxyphenylacetic acid(5),3-methylsulfinyl propionic acid(6),phenylacetic acid(7),(S)-N-nitroso-1-amino-p-hydroxy phenylethanol(8),2-phenylacetamide(9),p-hydroxybenzaldehyde(10),ethyl 2-(4-hydroxyphenyl)acetate(11),dibutyl phthalate(12),5,5'-dimethoxybiphenyl-2,2'-diol(13),3-indolealdehyde(14),N-acetyl-L-phenylalanine(15),9-hydroxy-10E,12Z-octadecadienoic acid(16),9-hydroxy-10E,12E-octadecadienoic acid(17),(6E)-5-methylene-6-tetradecenoic acid(18).CONCLUSION Compounds 1,3-8 and 10-18 are isolated from Candida sp for the first time.
4.Application of polyetheretherketone rod semi-rigid pedicle screw internal fixation in lumbar non-fusion surgery
Tao LIU ; Xing YU ; Jian-Bin GUAN ; Yong-Dong YANG ; He ZHAO ; Ji-Zhou YANG ; Yi QU ; Feng-Xian WANG ; Ding-Yan ZHAO ; Zi-Yi ZHAO
China Journal of Orthopaedics and Traumatology 2024;37(7):676-683
Objective To investigate the effect of Polyetheretherketone(PEEK)rod semi-rigid pedicle screw fixation sys-tem in lumbar spine non-fusion surgery.Methods A total of 74 patients with tow-level lumbar degenerative diseases who un-derwent surgery from March 2017 to December 2019 were divided into PEEK rod group and titanium rod group.In the PEEK rod group,there were 34 patients,including 13 males and 21 females,aged from 51 to 79 years old with an average of(62.4±6.8)years old;There were 1 patient of L1-L3 segments,7 patients of L2-L4 segments,20 patients of L3-L5 segments and 6 pa-tients of L4-S1 segments.In the titanium rod group,there were 40 patients,including 17 males and 23 females,aged from 52 to 81 years old with an average of(65.2±7.3)years old;There were 3 patient of L1-L3 segments,11 patients of L2-L4 segments,19 patients of L3-L5 segments and 7 patients of L4-S1 segments.The general conditions of operation,such as operation time,intraoperative blood loss,postoperative drainage was recorded.The visual analogue scale(VAS)for low back pain and Os-westry disability index(ODI)were compared in preoperatively and postoperatively(3 months,12 months and last follow-up)between two groups.The change of range of motion(ROM)was observed by flexion and extension x-ray of lumbar Results All patients successfully completed the operation.The follow-up time ranged from 22 to 34 months with an average of(26.8±5.6)months.The operative time(142.2±44.7)min and intraoperative blood loss(166.5±67.4)ml in PEEK group were lower than those in titanium group[(160.7±57.3)min、(212.8±85.4)ml](P<0.05).There was no significant differences in postoperative drainage between the two groups(P>0.05).At the final follow-up visit,in PEEK group and titanium group VAS of low back pain[(0.8±0.4)points vs(1.0±0.5)points],VAS for leg pain[(0.7±0.4)points vs(0.8±0.5)points]and ODI[(9.8±1.6)%vs(12.1±1.5)%]were compared with preoperative[(5.8±1.1)points vs(6.0±1.1)points],[(7.2±1.7)points vs(7.0±1.6)points],[(68.5±8.9)%vs(66.3±8.2)%]were significantly different(P<0.05).There was no significant difference in VAS scores between the two groups at each postoperative time point(P>0.05).At 3 months after surgery,there was no difference in ODI between the two groups(P>0.05).There were significant differences in ODI between PEEK group and titanium rod group at 12 months[(15.5±2.1)%vs(18.4±2.4)%]and at the last follow-up[(9.8±1.6)%vs(12.1±1.5)%](P<0.05).The total range of motion(ROM)of lumbar decreased in both groups after surgery.At 12 months after surgery and the last follow-up,the PEEK group compared with the titanium rod group,the total range of motion of lumbar was statistically significant(P<0.05).The range of motion(ROM)of the fixed segments decreased in both groups after surgery.The ROM of the fixed segments in PEEK group decreased from(9.5±4.6)° to(4.1±1.9)° at the last follow-up(P<0.05),which in the titanium rod group was de-creased from(9.8±4.3)°to(0.9±0.5)° at the last follow-up(P<0.05).The range of motion(ROM)of upper adjacent segment increased in both groups,there was statistical significance in the ROM of upper adjacent segment between the two groups at 12 months after surgery and the last follow-up,(P<0.05).There was no screw loosening and broken rods in both groups during the follow-up period.Conclusion The PEEK rod semi-rigid pedicle screw internal fixation system used in lumbar non-fusion surgery can retain part of the mobility of the fixed segment,showing comparable short-term clinical efficacy to titanium rod fu-sion.PEEK rod semi-rigid pedicle screw internal fixation system is a feasible choice for the treatment of lumbar spine degener-ative diseases,and its long-term efficacy needs further follow-up observation.
5.Research Progress on Detection of New Psychoactive Substance Piperazines in vivo
Jin-Ting LIU ; Li-Ying ZHOU ; Jia-Hong XIANG ; Zi-Yi LI ; Wan-Ting XIE ; Ke-Ming YUN ; Yan SHI
Journal of Forensic Medicine 2024;40(3):276-283
Piperazines are a class of new psychoactive substances with hallucinogenic effects that af-fect the central nervous system by affecting the level of monoamine neurotransmitters.Abuse of pipera-zines will produce stimulating and hallucinogenic effects,accompanied by headache,dizziness,anxiety,insomnia,vomiting,chest pain,tachycardia,hypertension and other adverse reactions,and may even cause cardiovascular diseases and multiple organ failure and lead to death,seriously affecting human physical and mental health and public safety.The abuse of new psychoactive substance piperazines has attracted extensive attention from the international community.The study of its pharmacological toxi-cology and analytical methods has become a research hotspot in the field of forensic medicine.This paper reviews the in vivo processes,sample treatment and analytical methods of existing piperazines,in order to provide reference for forensic identification.
6.Design of portable collection device for exhaled breath condensate
An XIANG ; Lei ZHOU ; Qi-Feng JI ; Yuan-Zhe LI ; Qin WANG ; Shi-Man ZHU ; Jie PENG ; Xiao-Ying LEI ; Wei-Na LI ; Li WANG ; Yan-Hai GUO ; Zi-Fan LU
Chinese Medical Equipment Journal 2024;45(8):32-37
Objective To develop a portable collection device of human exhaled breath condensate(EBC)based on natural breathing to meet the needs for rapid screening of human respiratory tract(especially lower respiratory tract)infections.Methods The device consisted of a refrigeration unit,a heat dissipation unit and a condensation unit.The refrigeration unit adopted a TES1-7102 thermoelectric Peltier cooler semiconductor as the refrigeration element;the heat dissipation unit was composed of a high thermal conductivity aluminum heat sink and a high-speed brushless cooling fan;the condensation unit was made up of a cold guide plate and a condenser,in which the cold guide plate was made of thin sheet of aluminum alloy,and the condenser was prepared by 3D printing technology and made of hydrophobic polylactic acid,with primary and secondary 2-stage guide grooves and an ultra-thin condensing surface.The performance of the device was verified in terms of cooling,thermal conductivity,condensation and human EBC collection and content analysis.Results Performance analysis showed that after refrigeration began the temperature difference between the condenser surface and the exhaled gas met the requirements of the condenser,and no obvious thermal resistance was found on the condensing surface so that large droplets could be formed rapidly and then be collected after the gas-liquid phase change of the exhaled gas on the condensing surface.Human EBC collection and content analysis indicated the device realized home self-collection of EBCs from people of all ages,and the concentrations of interleukins,C-reactive protein and other inflammation-related indexes and the pH value of the collected EBC samples were all correlated with respiratory infections in the subjects.Conclusion The device developed with easy operation avoids the discomfort of blowing collection and the risk of saliva contamination,and is worthy promoting for rapid diagnosis and dynamic monitoring of respiratory tract infection and other related diseases.[Chinese Medical Equipment Journal,2024,45(8):32-37]
7.Chemical and nutrient differences between medicinal material, residues, and residue compost of Moutan Cortex.
Rong-Qing ZHU ; Chun-Fang TIAN ; Xiao-Yan LAN ; Zi-Han WANG ; Xiang LI ; Li ZHOU ; Mei-Lan CHEN ; Li-Ping KANG
China Journal of Chinese Materia Medica 2023;48(23):6361-6370
Moutan Cortex(MC) residues produced after the extraction of MC can be re-extracted for active components and used to produce organic fertilizer and animal feed. However, they are currently disposed as domestic waste, which pollutes the environment. This study analyzed the chemical composition of the medicinal material, residues, and residue compost of MC by UPLC-UV-Q-TOF-MS. Furthermore, the nutrient composition of MC residues and the residue compost was analyzed. The results showed that:(1)MC residues had lower content of chemicals than the medicinal material, and content of paeonol, gallic acid, and galloylglucose in MC residues were about 1/3 of that in the medicinal material. The content of chemicals were further reduced after residue composting, and the quantitative compounds were all below the limits of detection.(2)Compared with MC residues, the residue compost showed the total nitrogen, total phosphorus, total potassium, and organic matter content increasing by 122.67%, 31.32%, 120.39%, and 32.06%, respectively. Therefore, we concluded that the MC residues can be used to re-extract active compounds such as paeonol, gallic acid, and galloylglucose. The MC residue compost is a high-quality organic fertilizer containing minimal content of chemicals and can be widely used in the cultivation of Chinese medicinal herbs.
Animals
;
Composting
;
Fertilizers
;
Soil/chemistry*
;
Hydrolyzable Tannins
;
Nutrients
;
Acetophenones
;
Drugs, Chinese Herbal
;
Paeonia
8.Development and validation of a score predicting mortality for older patients with mitral regurgitation.
De-Jing FENG ; Yun-Qing YE ; Zhe LI ; Bin ZHANG ; Qing-Rong LIU ; Wei-Wei WANG ; Zhen-Yan ZHAO ; Zheng ZHOU ; Qing-Hao ZHAO ; Zi-Kai YU ; Hai-Tong ZHANG ; Zhen-Ya DUAN ; Bin-Cheng WANG ; Jun-Xing LV ; Shuai GUO ; Run-Lin GAO ; Hai-Yan XU ; Yong-Jian WU
Journal of Geriatric Cardiology 2023;20(8):577-585
OBJECTIVE:
To develop and validate a user-friendly risk score for older mitral regurgitation (MR) patients, referred to as the Elder-MR score.
METHODS:
The China Senile Valvular Heart Disease (China-DVD) Cohort Study functioned as the development cohort, while the China Valvular Heart Disease (China-VHD) Study was employed for external validation. We included patients aged 60 years and above receiving medical treatment for moderate or severe MR (2274 patients in the development cohort and 1929 patients in the validation cohort). Candidate predictors were chosen using Cox's proportional hazards model and stepwise selection with Akaike's information criterion.
RESULTS:
Eight predictors were identified: age ≥ 75 years, body mass index < 20 kg/m2, NYHA class III/IV, secondary MR, anemia, estimated glomerular filtration rate < 60 mL/min per 1.73 m2, albumin < 35 g/L, and left ventricular ejection fraction < 60%. The model displayed satisfactory performance in predicting one-year mortality in both the development cohort (C-statistic = 0.73, 95% CI: 0.69-0.77, Brier score = 0.06) and the validation cohort (C-statistic = 0.73, 95% CI: 0.68-0.78, Brier score = 0.06). The Elder-MR score ranges from 0 to 15 points. At a one-year follow-up, each point increase in the Elder-MR score represents a 1.27-fold risk of death (HR = 1.27, 95% CI: 1.21-1.34, P < 0.001) in the development cohort and a 1.24-fold risk of death (HR = 1.24, 95% CI: 1.17-1.30, P < 0.001) in the validation cohort. Compared to EuroSCORE II, the Elder-MR score demonstrated superior predictive accuracy for one-year mortality in the validation cohort (C-statistic = 0.71 vs. 0.70, net reclassification improvement = 0.320, P < 0.01; integrated discrimination improvement = 0.029, P < 0.01).
CONCLUSIONS
The Elder-MR score may serve as an effective risk stratification tool to assist clinical decision-making in older MR patients.
9.Danhong Injection Up-regulates miR-125b in Endothelial Exosomes and Attenuates Apoptosis in Post-Infarction Myocardium.
Si-Nai LI ; Zi-Hao LIU ; Ming-Xue ZHOU ; Wei-Hong LIU ; Xiao-Lei LAI ; Ping LI ; Lei ZHANG ; Ju-Ju SHANG ; Sheng-Lei QIU ; Yan LOU ; Yu-Pei TAN ; Wen-Long XING ; Hong-Xu LIU
Chinese journal of integrative medicine 2023;29(12):1099-1110
OBJECTIVE:
To investigate the involvement of endothelial cells (ECs)-derived exosomes in the anti-apoptotic effect of Danhong Injection (DHI) and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis.
METHODS:
A mouse permanent myocardial infarction (MI) model was established, followed by a 14-day daily treatment with DHI, DHI plus GW4869 (an exosomal inhibitor), or saline. Phosphate-buffered saline (PBS)-induced ECs-derived exosomes were isolated, analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction (ddPCR). The exosomes induced by DHI (DHI-exo), PBS (PBS-exo), or DHI+GW4869 (GW-exo) were isolated and injected into the peri-infarct zone following MI. The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography, Masson's trichrome staining, and TUNEL apoptosis assay. The Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to evaluate the expression levels of miR-125b/p53-mediated pathway components, including miR-125b, p53, Bak, Bax, and caspase-3 activities.
RESULTS:
DHI significantly improved cardiac function and reduced infarct size in MI mice (P<0.01), which was abolished by the GW4869 intervention. DHI promoted the exosomal secretion in ECs (P<0.01). According to the results of exosomal miRNA microarray assay, 30 differentially expressed miRNAs in the DHI-exo were identified (28 up-regulated miRNAs and 2 down-regulated miRNAs). Among them, DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs, a recognized apoptotic inhibitor impeding p53 signaling (P<0.05). Remarkably, treatment with DHI and DHI-exo attenuated apoptosis, elevated miR-125b expression level, inhibited capsase-3 activity, and down-regulated the expression levels of proapoptotic effectors (p53, Bak, and Bax) in post-MI hearts, whereas these effects were blocked by GW4869 (P<0.05 or P<0.01).
CONCLUSION
DHI and DHI-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in post-infarction myocardium.
Mice
;
Animals
;
Tumor Suppressor Protein p53/metabolism*
;
Endothelial Cells/metabolism*
;
Exosomes/metabolism*
;
bcl-2-Associated X Protein/metabolism*
;
Myocardium/metabolism*
;
Myocardial Infarction/drug therapy*
;
Apoptosis
;
MicroRNAs/metabolism*
10. Expression, purification and functional verification of recombinant human α-galactosidase A in suspension CHO-S
Mu-Lan DENG ; Hong-Yu ZHOU ; Ke-Xin ZHENG ; Zhao-Yang LI ; Wan-Yi GUO ; Yan-Ping WANG ; Zhi-Cheng LIANG ; Fang-Hong LI ; Yun-Ping MU ; Zi-Jian ZHAO
Chinese Pharmacological Bulletin 2023;39(4):774-781
Aim To express and purify rhα-Gal A with a 6 X His tag via using a serum-free expression system in high-density suspension culture of Chinese hamster ovary cells ( CHO-S) , and to verify the scavenging effect of rhα-Gal A on globular trisaccharide ceramide (Gb3 or GL3) . Methods The construction of recombinant protein expression vector, pcDNA4-GLA, was achieved by fusing the human α-galactosidase cDNA, gla, with 6 X His tag and artificial DNA synthesis. The expression plasmid was transfected into the suspended CHO-S to express rhα-Gal A and then purified. Following this procedure, we determined rhα-Gal A's expression, the enzymatic activity, and the glycosylation of the recombinant enzyme. Co-incubation with cultured cells was performed to examine whether rhα-Gal A could be taken up into the cells and effectively remove Gb3 substrates. Results rhα-Gal A was successfully expressed and purified after transiently transfecting pcDNA4-GLA into the suspended CHO-S, and the yield was up to (100 ±20. 6) mg • L

Result Analysis
Print
Save
E-mail