1.6-Week Caloric Restriction Improves Lipopolysaccharide-induced Septic Cardiomyopathy by Modulating SIRT3
Ming-Chen ZHANG ; Hui ZHANG ; Ting-Ting LI ; Ming-Hua CHEN ; Xiao-Wen WANG ; Zhong-Guang SUN
Progress in Biochemistry and Biophysics 2025;52(7):1878-1889
ObjectiveThe aim of this study was to investigate the prophylactic effects of caloric restriction (CR) on lipopolysaccharide (LPS)-induced septic cardiomyopathy (SCM) and to elucidate the mechanisms underlying the cardioprotective actions of CR. This research aims to provide innovative strategies and theoretical support for the prevention of SCM. MethodsA total of forty-eight 8-week-old male C57BL/6 mice, weighing between 20-25 g, were randomly assigned to 4 distinct groups, each consisting of 12 mice. The groups were designated as follows: CON (control), LPS, CR, and CR+LPS. Prior to the initiation of the CR protocol, the CR and CR+LPS groups underwent a 2-week acclimatization period during which individual food consumption was measured. The initial week of CR intervention was set at 80% of the baseline intake, followed by a reduction to 60% for the subsequent 5 weeks. After 6-week CR intervention, all 4 groups received an intraperitoneal injection of either normal saline or LPS (10 mg/kg). Twelve hours post-injection, heart function was assessed, and subsequently, heart and blood samples were collected. Serum inflammatory markers were quantified using enzyme-linked immunosorbent assay (ELISA). The serum myocardial enzyme spectrum was analyzed using an automated biochemical instrument. Myocardial tissue sections underwent hematoxylin and eosin (HE) staining and immunofluorescence (IF) staining. Western blot analysis was used to detect the expression of protein in myocardial tissue, including inflammatory markers (TNF-α, IL-9, IL-18), oxidative stress markers (iNOS, SOD2), pro-apoptotic markers (Bax/Bcl-2 ratio, CASP3), and SIRT3/SIRT6. ResultsTwelve hours after LPS injection, there was a significant decrease in ejection fraction (EF) and fractional shortening (FS) ratios, along with a notable increase in left ventricular end-systolic diameter (LVESD). Morphological and serum indicators (AST, LDH, CK, and CK-MB) indicated that LPS injection could induce myocardial structural disorders and myocardial injury. Furthermore, 6-week CR effectively prevented the myocardial injury. LPS injection also significantly increased the circulating inflammatory levels (IL-1β, TNF-α) in mice. IF and Western blot analyses revealed that LPS injection significantly up-regulating the expression of inflammatory-related proteins (TNF-α, IL-9, IL-18), oxidative stress-related proteins (iNOS, SOD2) and apoptotic proteins (Bax/Bcl-2 ratio, CASP3) in myocardial tissue. 6-week CR intervention significantly reduced circulating inflammatory levels and downregulated the expression of inflammatory, oxidative stress-related proteins and pro-apoptotic level in myocardial tissue. Additionally, LPS injection significantly downregulated the expression of SIRT3 and SIRT6 proteins in myocardial tissue, and CR intervention could restore the expression of SIRT3 proteins. ConclusionA 6-week CR could prevent LPS-induced septic cardiomyopathy, including cardiac function decline, myocardial structural damage, inflammation, oxidative stress, and apoptosis. The mechanism may be associated with the regulation of SIRT3 expression in myocardial tissue.
2.Effect of different detector combinations on head CT image quality and radiation dose in 320-row CT
Yun LUO ; Ming-ran SHAO ; Shang-wen YANG ; Yu-xiao WANG ; Kang SHI ; Ya-yun XU
Chinese Medical Equipment Journal 2025;46(4):57-62
Objective To compare the effects of different detector combinations of 320-row CT on the image quality and radiation dose of head CT to explore the feasibility of using a wide detector for head CT scanning.Methods Totally 100 patients underwent head CT scanning due to trauma or cerebrovascular disease at some hospital from June to August 2023 were collected prospectively and divided into group A and group B by using block randomization grouping method,with the length of the block group being 2 and 50 patients in each group.In group A,all the detectors had the widths at z-axis direction being 40×0.5 mm and head scanning was completed after multiple exposures;in group B,detector combinations with widths of 280×0.5 mm or 320×0.5 mm were chosen based on the patient's head size in the head-foot direction(z-axis direction),and head scanning was performed with a single-turn exposure.The remaining scanning and image reconstruction parameters in the two groups were kept completely consistent.The head image quality of the 2 groups was evaluated objectively and scored subjectively by 2 radiologists.The volume CT dose index(CTDIvol),dose length product(DLP)and exposure time of the 2 groups were recorded,and the effective dose(ED)was calculated.SPSS 22.0 software was used for statistical analysis.Results In terms of objective evaluation of image quality,at the level of the parietal skull group B had the CT value of gray matter,image noise and contrast to noise ratio(CNR)of the images higher than those of group A,and the differences were statistically significant(all P<0.05);at the level of the posterior skull group B had the CT values of gray and white matter,image noise and air noise lower while CNR higher than those of group A,and the differences were statistically significant(all P<0.05).In terms of subjective scoring of image quality,at the levels of parietal and posterior skull group A behaved better than group B,and the differences were statistically significant(all P<0.05).In group A 5 patients had obvious motion artifacts affecting the diagnosis and the image quality scores not higher than 2,and secondary scanning had to be carried out;In group B all the patients had no obvious motion artifacts and met the diagnosis requirements.When compared with group A Group B had the CTDIvol,DLP,ED and exposure time decreased by 17.44%,17.24%,17.48%and 85.53%,respectively,and the differences were statistically significant(all P<0.05).Conclusion A wide detector gains advantages over a 20 mm detector in image quality when 320-row CT is used for head CT scanning,with the diagnosis requirements satisfied.[Chinese Medical Equipment Journal,2025,46(4):57-62]
3.Effects of Yiqi Jiedu Tongluo Formula on renal injury in a rat model of type 2 diabetes mellitus via TGF-β/SMAD and VEGF pathways
Wen-xuan XU ; Lei-lei MA ; Ming-yu SHEN ; Xiao-jin LA ; Bi-wei ZHANG ; Shuo WANG ; Chao LI ; Peng CUI ; Zhen CHEN ; Ji-an LI
Chinese Traditional Patent Medicine 2025;47(2):421-429
AIM To observe the effects of Yiqi Jiedu Tongluo Formula(YQJDTL)on renal microvascular endothelial function and prevention of renal injury in a rat model of type 2 diabetes mellitus(T2DM).METHODS The SD rats were randomly divided into a normal group and a model group.The model group was administered with high-fat diet combined with a single intraperitoneal injection of STZ to establish the T2DM model.The successfully modeled rats were randomly divided into the model group,the canagliflozin group(9 mg/kg),and the low-dose and high-dose YQJDTL groups(4.77,9.45 g/kg).The corresponding doses of the drug were administered by gavage for a total of 12 weeks,during which the rats underwent observation of their general condition and blood glucose changes.After the end of administration,the rats had their levels of renal index,24-hour UP,serum SCr,BUN,TC,TG,HDL-C,LDL-C,ET-1 and NOS measured;their changes in renal microvasculature and the degree of renal fibrosis observed using HE staining,Masson staining,PAS staining,and PASM staining;their ultrastructure of the glomeruli observed using transmission electron microscopy;their renal protein expressions of TGF-β,SMAD2,SMAD3,Col-1,VEGFA and PKC detected by immunohistochemical staining and Western blot;and their renal mRNA expressions of VEGFA,TGF-β,SMAD2 determined by RT-qPCR.RESULTS Compared with the model group,the high-dose YQJDTL group showed decreased levels of renal index,blood glucose,TG,TC,HDL,24 h UP,BUN,SCr and ET-1(P<0.05,P<0.01);increased LDL and NOS levels(P<0.05,P<0.01);reduced renal inflammatory infiltration and fibrosis degree,inhibited fusion of foot processes and thickening of basement membrane;decreased renal protein expressions of TGF-β,SMAD2,SMAD3,VEGFA,PKC and Col-1(P<0.05,P<0.01);and decreased mRNA expressions of VEGFA,TGF-β and SMAD2(P<0.01).CONCLUSION In the rat models of T2DM,YQJDTL can reduce their levels of blood glucose and lipids by improving the renal indices levels and the renal microvascular endothelial functions to alleviate renal fibrosis and microangiopathy as well,and the mechanism may be associated with the down-regulated expressions of TGF-β/SMAD and VEGF pathway-related proteins.
4.Lycium barbarum polysaccharide ameliorates ovarian granulosa cell aging in rats by activating CAMKK2/AMPK/MCU signaling pathway
Xiao-dan LIU ; Chen LING ; Lu LIU ; Jing PU ; Hai-bin MA ; Hui-ming MA ; Wen-ping ZHANG ; Dong-mei CHEN
Chinese Pharmacological Bulletin 2025;41(6):1116-1125
Aim To explore the mechanism of Lycium barbarum glycopeptide(LbGP)improving aging in rat primary ovarian granulosa cells.Methods This study divided the cells into a normal group,a DOX group,and four different LbGP concentration treatment groups post-DOX intervention.Results Cell proliferation was assessed using CCK-8,EDU,and Ki67 assays,while aging markers and mitochondrial function-related fac-tors were detected using immunofluorescence and West-ern blotting.The results showed that,compared to the DOX group,LbGP treatment significantly increased cell viability(P<0.05)and promoted proliferation(P<0.05).Post LbGP treatment,the β-galactosidase-posi-tive area in cells was significantly reduced compared to the DOX group(P<0.05).Immunofluorescence re-sults indicated that,compared to the DOX group,levels of p21 and γH2AX significantly decreased(P<0.05),while pRB increased(P<0.05)after LbGP treatment.Western blot results showed that,compared to the DOX group,the aging phenotype proteins p21 and p53 significantly decreased(P<0.05),and pRB notably increased(P<0.05)in the LbGP treatment group.The release of cytC into the cytoplasm and the activated caspase-9 significantly decreased(P<0.05);levels of CAMKK2,pAMPK,and mitochondrial calcium homeostasis regulator MCU increased(P<0.05);nuclear energy metabolism-related proteins SirT1,PGC1α/β and ATP5A1 significantly increased(P<0.05);compared to the DOX group,ROS levels significantly decreased after LbGP treatment(P<0.05).Conclusions The results suggest that LbGP can ameliorate DOX-induced aging in rat primary ovar-ian granulosa cells,potentially through the upregulation of the CAMKKβ/AMPK signaling pathway,thereby im-proving mitochondrial calcium homeostasis and increas-ing the expression levels of cell energy metabolism-re-lated regulatory proteins.This provides an experimen-tal basis for LbGP's potential role in supporting the im-provement of ovarian function.
5.Impacts of advanced male age on sperm DNA methylation and subsequent development of embryos and offspring
Wen LIU ; Ge FANG ; Xiao LI ; Shao-ming LU
National Journal of Andrology 2025;31(2):172-176
Male factors contribute to infertility at roughly the same rate as female factors,and sperm DNA methylation in ad-vanced-aged males directly affects semen parameters and significantly reduces fertility and increases the miscarriage rate of spouses.Many adverse outcomes of reproductive health are associated with advanced reproductive age of men,and few studies are reported on the influence of paternal age on the health of the offspring.The role of advanced age in human sperm DNA methylation variation and mechanism of its subsequent influence on the offspring health remain unclear.Attention should be paid to the influence of reproductive age on pregnancy outcomes in this population.This reviews focuses on the impacts of advanced male age on sperm DNA methylation and consequently on reproductive outcomes and the offspring,with elucidation of its underlying mechanisms,aiming to provide some more useful evidence for solving related clinical problems.
6.Establishment of preparation process and quality standard for Zhenggu Pills
Wen-ming ZHANG ; Zi-fang FENG ; Li-hong GU ; Ping QIN ; Zhen-hua BIAN ; Min-min HU ; Xiao-wei CHEN
Chinese Traditional Patent Medicine 2025;47(9):2863-2869
AIM To establish the preparation process and quality standard for Zhenggu Pills.METHODS With decoction time,decoction frequency and water addition as influencing factors,comprehensive score for extract yield and transfer rates of epicatechin and naringin as an evaluation index,the decoction process was optimized by orthogonal test.With sugarless paste relative density,medicinal powder fineness,sugarless paste-corn starch ratio,drying temperature and drying time as influencing factors,soft material traits,pill formability,moisture and disintegration time limit as evaluation indices,the formability process was optimized by single factor test.TLC was adopted in the qualitative identification of Dipsaci Radix,salt-processed Psoraleae Fructus,cooked Rhei Radix et Rhizoma and Notoginseng Radix et Rhizoma.HPLC was used for the content determination of paeoniflorin and naringin.RESULTS The optimal decoction process was determined to be 0.5 h for decoction time,two times for decoction frequency,and 10 times for water addition,the comprehensive score was 0.93.The optimal formability process was determined to be 1.21-1.22 for sugarless paste relative density,80 mesh for medicinal powder fineness,1∶0.17-1∶0.18 for sugarless paste-corn starch ratio,70 ℃ for drying temperature,and 24 h for drying time,good soft material traits and pill formability were observable,and moisture and disintegration time limit accored with 2020 edition of Chinese Pharmacopoeia requirements.The TLC spots were clear without negative interference.Two constituents showed good linear relationships within 61.30-490.41 μg/mL(r=0.999 8)and 3.27-26.18 μg/mL(r=0.999 8),whose average recoveries were 100.15%and 98.15%with the RSDs of 0.55%and 2.30%,respectively.CONCLUSION This stable,reliable and specific method can be used for the production and quality evaluation of Zhenggu Pills.
7.Establishment of quantitative models for effective components in Yishen Xiezhuo Mixture
Zi-fang FENG ; Min-min HU ; Xiao-wei CHEN ; Wen-ming ZHANG ; Li-hong GU ; Ping QIN ; Yi PENG ; Zhen-hua BIAN ; Qing-you YANG ; Tu-lin LU
Chinese Traditional Patent Medicine 2025;47(10):3177-3184
AIM To establish the quantitative models for gallic acid,mononucleoside,loganin,resveratrol,and rhein in Yishen Xiezhuo Mixture.METHODS HPLC was adopted in the content determination of various effective components,after which the near-infrared spectroscopy(NIRS)data were collected in 128 batches of samples and pretreatment was conducted,competitive adaptive reweighting sampling(CARS)algorithm was used for screening wavelength,partial least square method(PLS)regression analysis was performed.RESULTS There were no significant differences between the predicted values obtained by PLS models and measured values obtained by HPLC for various effective components(P>0.05).CONCLUSION The quantitative models established by NIRS combined with chemometrics display good predictive performance,which can be used for the rapid determination of effective components in Yishen Xiezhuo Mixture,and provide a reference for the rapid monitoring of other traditional Chinese medicine preparations in production processes.
8.Effects of Yiqi Jiedu Tongluo Formula on renal injury in a rat model of type 2 diabetes mellitus via TGF-β/SMAD and VEGF pathways
Wen-xuan XU ; Lei-lei MA ; Ming-yu SHEN ; Xiao-jin LA ; Bi-wei ZHANG ; Shuo WANG ; Chao LI ; Peng CUI ; Zhen CHEN ; Ji-an LI
Chinese Traditional Patent Medicine 2025;47(2):421-429
AIM To observe the effects of Yiqi Jiedu Tongluo Formula(YQJDTL)on renal microvascular endothelial function and prevention of renal injury in a rat model of type 2 diabetes mellitus(T2DM).METHODS The SD rats were randomly divided into a normal group and a model group.The model group was administered with high-fat diet combined with a single intraperitoneal injection of STZ to establish the T2DM model.The successfully modeled rats were randomly divided into the model group,the canagliflozin group(9 mg/kg),and the low-dose and high-dose YQJDTL groups(4.77,9.45 g/kg).The corresponding doses of the drug were administered by gavage for a total of 12 weeks,during which the rats underwent observation of their general condition and blood glucose changes.After the end of administration,the rats had their levels of renal index,24-hour UP,serum SCr,BUN,TC,TG,HDL-C,LDL-C,ET-1 and NOS measured;their changes in renal microvasculature and the degree of renal fibrosis observed using HE staining,Masson staining,PAS staining,and PASM staining;their ultrastructure of the glomeruli observed using transmission electron microscopy;their renal protein expressions of TGF-β,SMAD2,SMAD3,Col-1,VEGFA and PKC detected by immunohistochemical staining and Western blot;and their renal mRNA expressions of VEGFA,TGF-β,SMAD2 determined by RT-qPCR.RESULTS Compared with the model group,the high-dose YQJDTL group showed decreased levels of renal index,blood glucose,TG,TC,HDL,24 h UP,BUN,SCr and ET-1(P<0.05,P<0.01);increased LDL and NOS levels(P<0.05,P<0.01);reduced renal inflammatory infiltration and fibrosis degree,inhibited fusion of foot processes and thickening of basement membrane;decreased renal protein expressions of TGF-β,SMAD2,SMAD3,VEGFA,PKC and Col-1(P<0.05,P<0.01);and decreased mRNA expressions of VEGFA,TGF-β and SMAD2(P<0.01).CONCLUSION In the rat models of T2DM,YQJDTL can reduce their levels of blood glucose and lipids by improving the renal indices levels and the renal microvascular endothelial functions to alleviate renal fibrosis and microangiopathy as well,and the mechanism may be associated with the down-regulated expressions of TGF-β/SMAD and VEGF pathway-related proteins.
9.Enhancement of Ca2+ Signal Strength in Astrocytes in the Lateral Septum Improves Cognitive Disorders in Mice After Hemorrhagic Shock and Resuscitation.
Wen-Guang LI ; Lan-Xin LI ; Rong-Xin SONG ; Xu-Peng WANG ; Shi-Yan JIA ; Xiao-Yi MA ; Jing-Yu ZHANG ; Gang-Feng YIN ; Xiao-Ming LI ; Li-Min ZHANG
Neuroscience Bulletin 2025;41(8):1403-1417
Hemorrhagic shock is a common clinical emergency that can aggravate cell injury after resuscitation. Astrocytes are crucial for the survival of neurons because they regulate the surrounding ionic microenvironment of neurons. Although hemorrhagic shock and resuscitation (HSR) injury can impair cognition, it remains unclear how this insult directly affects astrocytes. In this study, we established an HSR model by bleeding and re-transfusion in mice. The social interaction test and new object recognition test were applied to evaluate post-operative cognitive changes, and the results suggest that mice experience cognitive impairment following exposure to HSR. In the HSR group, the power spectral density of β and γ oscillations decreased, and the coupling of the θ oscillation phase and γ oscillation amplitude was abnormal, which indicated abnormal neuronal oscillation and cognitive impairment after HSR exposure. In brief, cognitive impairment in mice is strongly correlated with Ca2+ signal strength in lateral septum astrocytes following HSR.
Animals
;
Astrocytes/metabolism*
;
Shock, Hemorrhagic/metabolism*
;
Resuscitation/adverse effects*
;
Male
;
Mice
;
Calcium Signaling/physiology*
;
Mice, Inbred C57BL
;
Septal Nuclei/metabolism*
;
Cognitive Dysfunction/etiology*
;
Disease Models, Animal
;
Cognition Disorders/etiology*
10.Xinyang Tablets ameliorate ventricular remodeling in heart failure via FTO/m6A signaling pathway.
Dong-Hua LIU ; Zi-Ru LI ; Si-Jing LI ; Xing-Ling HE ; Xiao-Jiao ZHANG ; Shi-Hao NI ; Wen-Jie LONG ; Hui-Li LIAO ; Zhong-Qi YANG ; Xiao-Ming DONG
China Journal of Chinese Materia Medica 2025;50(4):1075-1086
The study was conducted to investigate the mechanism of Xinyang Tablets( XYP) in modulating the fat mass and obesity-associated protein(FTO)/N6-methyladenosine(m6A) signaling pathway to ameliorate ventricular remodeling in heart failure(HF). A mouse model of HF was established by transverse aortic constriction(TAC). Mice were randomized into sham, model, XYP(low, medium, and high doses), and positive control( perindopril) groups(n= 10). From day 3 post-surgery, mice were administrated with corresponding drugs by gavage for 6 consecutive weeks. Following the treatment, echocardiography was employed to evaluate the cardiac function, and RT-qPCR was employed to determine the relative m RNA levels of key markers, including atrial natriuretic peptide( ANP), B-type natriuretic peptide( BNP), β-myosin heavy chain(β-MHC), collagen type I alpha chain(Col1α), collagen type Ⅲ alpha chain(Col3α), alpha smooth muscle actin(α-SMA), and FTO. The cardiac tissue was stained with Masson's trichrome and wheat germ agglutinin(WGA) to reveal the pathological changes. Immunohistochemistry was employed to detect the expression levels of Col1α, Col3α, α-SMA, and FTO in the myocardial tissue. The m6A modification level in the myocardial tissue was measured by the m6A assay kit. An H9c2 cell model of cardiomyocyte injury was induced by angiotensin Ⅱ(AngⅡ), and small interfering RNA(siRNA) was employed to knock down FTO expression. RT-qPCR was conducted to assess the relative m RNA levels of FTO and other genes associated with cardiac remodeling. The m6A modification level was measured by the m6A assay kit, and Western blot was employed to determine the phosphorylated phosphatidylinositol 3-kinase(p-PI3K)/phosphatidylinositol 3-kinase(PI3K) and phosphorylated serine/threonine kinase(p-Akt)/serine/threonine kinase(Akt) ratios in cardiomyocytes. The results of animal experiments showed that the XYP treatment significantly improved the cardiac function, reduced fibrosis, up-regulated the m RNA and protein levels of FTO, and lowered the m6A modification level compared with the model group. The results of cell experiments showed that the XYP-containing serum markedly up-regulated the m RNA level of FTO while decreasing the m6A modification level and the p-PI3K/PI3K and p-Akt/Akt ratios in cardiomyocytes. Furthermore, FTO knockdown reversed the protective effects of XYP-containing serum on Ang Ⅱ-induced cardiomyocyte hypertrophy. In conclusion, XYP may ameliorate ventricular remodeling by regulating the FTO/m6A axis, thereby inhibiting the activation of the PI3K/Akt signaling pathway.
Animals
;
Ventricular Remodeling/drug effects*
;
Heart Failure/physiopathology*
;
Signal Transduction/drug effects*
;
Mice
;
Male
;
Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics*
;
Drugs, Chinese Herbal/administration & dosage*
;
Mice, Inbred C57BL
;
Humans
;
Adenosine/analogs & derivatives*
;
Myocytes, Cardiac/metabolism*
;
Disease Models, Animal

Result Analysis
Print
Save
E-mail