OBJECTIVETo study the effects of the divided functional recipes of Dahuang Zhechong pill( DHZCP) on atherosclerosis in rabbits.

METHODThe atherosclerotic model was established by the combination of hypercholesterol feeding and immune-injured endothelium in rabbits. Male New Zealand rabbits were randomly divided into nine groups: normal group, model group, Danshen group (0. 5 g x kg(-1) ), the low-dose(0. 5 g x kg(-1) ) and high-dose( 1.0 g - kg(-1) ) groups of the first divided recipe, the low-dose(0. 75 g x kg-' ) and high-dose(1. 5 g x kg(-1)) groups of the second divided recipe, the low-dose(0. 8 g x kg(-1) ) and high-dose( 1.6 g x kg(-1) ) groups of the third divided recipe. The effects of the divided functional recipes of DHZCP were observed in macropathology, histopathology and ultrastructure. Image analyzing system was used to determine atherosclerotic plaque area, intima thickness(IT) and intima-media thickness(IMT) in rabbit aorta.

RESULTThe divided functional recipes of DHZCP could significantly decreased the deposit of lipid and the atherosclerotic plaque area in aorta intima, relieve the histopathological changes of atherosclerosis, and inhibited the proliferation of vascular smooth muscle cells and collagen to reduce pachynsis of vascular intima. The divided functional recipes of DHZCP also reduced IT, IMT and IT/MT and reversed the contractive vascular remodeling.

CONCLUSIONThe divided functional recipes of DHZCP produce the different anti-atherosclerotic action, among which the first divided functional recipe exhibits more effective action.

Animals ; Aorta ; drug effects ; pathology ; ultrastructure ; Atherosclerosis ; pathology ; prevention & control ; Cell Proliferation ; drug effects ; Cockroaches ; chemistry ; Dose-Response Relationship, Drug ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; therapeutic use ; Male ; Medicine, Chinese Traditional ; Microscopy, Electron ; Myocytes, Smooth Muscle ; drug effects ; pathology ; ultrastructure ; Plants, Medicinal ; chemistry ; Rabbits ; Random Allocation ; Rheum ; chemistry ; Tunica Intima ; drug effects ; pathology

AIM To prepare Scutellariae Radix total flavonoids-loaded liposomes and to evaluate their in vitro anti-tumor activity.METHODS Liposomes were prepared by reverse evaporating method.Taking phospholipid concentration,ratio of phospholipid to cholesterol,ratio of organic phase to aqueous phase and total flavonoids concentration as influencing factors,together with encapsulation efficiency as an evaluation index,Box-Behnken design was applied to optimizing the preparation,after which MTT was employed to detect the obtained liposomes' inhibitory effect on human hepatocellular carcinoma cells HepG2.RESULTS The optimal conditions were determined to be 30 mg/mL for phospholipid concentration,3 ∶ 1 for ratio of phospholipid to cholesterol,2 ∶ 1 for ratio of organic phase to aqueous phase,and 5 mg/mL for total flavonoids concentration.The obtained round and uniform liposomes demonstrated an average particle size of (160.7 ± 12.0) nm,Zeta potential of (-41.4 ±2.3) mV,encapsulation efficiency of (86.19 ±0.44)％,drug loading of (5.32 ± 0.04)％,and accumulative release rate of (80.77 ± 2.53) ％ at 24 h.Compared with total flavonoids,liposomes exhibited stronger inhibitory effect on HepG2 cells with the IC50 of 48.853 μg/mL at 48 h in a time-and dose-dependent manner.CONCLUSION Scutellariae Radix total flavonoids-loaded liposomes stored at low temperature (4 ℃) display sustained-release effect and in vitro anti-tumor activity.

The prevalence of cardiovascular disease in our country is increasing, and it has been a big problem affecting the social and economic development. It has been demonstrated that early intervention of cardiovascular risk factors can effectively reduce cardiovascular disease-caused mortality. Therefore, extensive implementation of cardiovascular testing and risk factor screening in the general population is the key to the prevention and treatment of cardiovascular disease. However, the categories of devices available for quick cardiovascular testing are limited, and in particular, many existing devices suffer from various technical problems, such as complex operation, unclear working principle, or large inter-individual variability in measurement accuracy, which lead to an overall low popularity and reliability of cardiovascular testing. In this study, we introduce the non-invasive measurement mechanisms and relevant technical progresses for several typical cardiovascular indices (e.g., peripheral/central arterial blood pressure, and arterial stiffness), with emphasis on describing the applications of biomechanical modeling and simulation in mechanism verification, analysis of influential factors, and technical improvement/innovation.
Arterial Pressure ; Biomechanical Phenomena ; Blood Pressure ; Blood Pressure Determination ; Humans ; Reproducibility of Results ; Risk Factors

OBJECTIVESTo evaluate the expression profile of myoD microRNA-29 (miR-29) family in L6 myoblast differentiated to myotube of L6 myotube treated by glucose and insulin, and to further probe the molecular mechanism of myoD regulating the expression of miR-29 clusters.

METHODSThe expression of myoD and miR-29 family was detected by using real-time PCR and Western blot analysis. The potential promoter and transcription factors binding sites of miR-29 clusters were predicted by Promoter scan and transcriptional factor search. The promoter sequence of miR-29b1-a and miR-29b2-c cluster was cloned into a luciferase reporter plasmid and the regulatory effect of myoD was analyzed by using dual luciferase reporter assay. Electrophoretic mobility shift assay was further conducted to indicate the binding of myoD on specific sequence. Moreover, overexpression of myoD was achieved by a recombinant adenovirus system (Ad-myoD). L6 cells were infected with Ad-myoD and real-time PCR was conducted to analyze the expression of miR-29b and miR-29c.

RESULTSThe expression levels of myoD, miR-29a, miR-29b, and miR-29c were increased in L6 myoblast differentiated to myotube. The expression of myoD, miR-29b, and miR-29c was up-regulated in L6 myotube treated with glucose and insulin, but miR-29a depicted no significant change. Dual luciferase reporter gene assay showed that myoD functioned as a positive regulator of miR-29b2-c expression and myoD could bind to the specific sequence located at the promoter region of miR-29b2-c cluster. Enforced expression of myoD led to a marked increase of miR-29b and miR-29c levels in L6 cells.

CONCLUSIONMyoD might act as a crucial regulator of myogenesis and glucose metabolism in muscle through regulating the expression of miR-29b2-c.

Animals ; Cell Differentiation ; drug effects ; physiology ; Cell Line ; Gene Expression Regulation ; drug effects ; physiology ; Glucose ; pharmacology ; Hypoglycemic Agents ; pharmacology ; Insulin ; pharmacology ; Mice ; MicroRNAs ; biosynthesis ; genetics ; Multigene Family ; physiology ; Muscle Fibers, Skeletal ; cytology ; metabolism ; MyoD Protein ; genetics ; metabolism ; Myoblasts ; cytology ; metabolism ; Sweetening Agents ; pharmacology

The goal of this work was to establish a population pharmacokinetics (PPK) model of tacrolimus in idiopathic membranous nephropathy (IMN) patients and to identify potential covariates that influence pharmacokinetic of tacrolimus. A total of 610 data points on the blood concentration of tacrolimus were collected from 96 IMN patients in routine clinical settings. Nonlinear mixed-effect modeling (NONMEM) was used to investigate the effects of CYP3A5 genotype, age, gender, weight, laboratory tests and co-therapy medications on the pharmacokinetic of tacrolimus. The PPK model was evaluated by the goodness-of-fit (GOT), bootstrap and prediction corrected visual predictive check (pc-VPC). The pharmacokinetic of tacrolimus was described by a one-compartment model. The apparent clearance (CL/F) of CYP3A5*1/*3 and *1/*1 were 1.57 and 1.86 times of that of *3/*3, respectively. The CL/F of tacrolimus was 73.6% in patients undergoing co-therapy with Wuzhi capsules, and 1.2 times than that of the patients undergoing co-therapy with Jinshuibao capsules. The evaluation of the model shows that the model is stable and has satisfactory predictive performance. The clinical trial was approved by the Society of Ethics and conducted in Binzhou Medical University Hospital. The established PPK model can describe the pharmacokinetic characteristics of tacrolimus in Chinese patients with IMN, and can facilitate individualized therapy with tacrolimus.

ObjectiveTo analyze the clinical characteristics and the use of traditional Chinese medicine （TCM） therapy in cancer patients with COVID-19， and to provide reference for making TCM prevention and treatment strategies and determining diagnosis and treatment priorities for patients with malignant tumors in the COVID-19 epidemic. MethodsThe medical records of 225 malignant tumor cases with COVID-19 who were admitted to 7 national research centers from January 1st to 20th， 2023 were retrospectively collected， and the main symptoms and duration after infection， nucleic acid negative conversion time， use of TCM therapy， and changes in adverse reactions after resuming anti-tumor treatment were analyzed. ResultsA total of 222 malignant tumor patients with COVID-19 were included in the analysis， involving 205 mild cases and 17 moderate cases. The top four most frequently reported clinical symptoms were fever （165 cases）， expectoration or dry cough （99 cases）， decreased appetite （95 cases） and fatigue （85 cases）， of which 40 expectoration or dry cough cases ， 37 fatigue cases and 29 decreased appetite cases lasted for more than 14 days. One hundred and five patients with nucleic acid detection report had a median negative conversion time of 14 days. The nucleic acid negative conversion time was significantly longer in patients with lung cancer compared to those with digestive system malignant tumors， and in those with myelosuppression than those without （P＜0.01）. During the infection period， 47.30% （105/222） of the patients used Chinese patent medicine， and 21.17% （47/222） were treated with herbal decoctions. The use of TCM in patients during the prevention and rehabilitation period， was 1.80%（4/222） and 7.21%（16/222）， respectively. Fifty-five patients resumed anti-tumor treatment after nucleic acid negative conversion， and received TCM simultaneously. Observed adverse reactions， including gastrointestinal reactions， bone marrow suppression， and neurotoxicity， were all grade 1 to 2， and no new adverse events occurred during follow-up. ConclusionCertain malignant tumor patients with COVID-19 had prolonged symptoms and nucleic acid negative conversion time Rational use of TCM can help to promote the rehabilitation of the patients and ensure the smooth process of anti-tumor treatment after infection.

Objective To investigate the correlation between MEX3A and differentiation characteristics of gastric cancer and intestinal metaplasia,and its combination with caudal-related homeobox transcription factor 2(CDX2)and mucin 2(MUC2)and mucin 5AC(MUC5AC)to determine the role of carcinogenic intestinal metaplasia.Methods From January 2010 to December 2014,a total of 410 cases of gastric cancer and paracarcinoma paraffin-embedded tissue samples were selected from the Central Hospital Affiliated to Shenyang Medical College and the Second Hospital Affiliated to Shenyang Medical College.According to pathological diagnosis,they were divided into control group(mild superficial gastritis,79 cases),intestinal metaplasia group(149 cases)and gastric cancer group(182 cases).The expressions of MEX3A,CDX2,MUC2 and MUC5AC were detected by immunohistochemistry.Results MEX3A was highly expressed in gastric cancer group and intestinal metaplasia group,especially diffuse gastric cancer,poorly differentiated gastric cancer and type Ⅲ intestinal metaplasia(P<0.05).CDX2 and MUC2 were highly expressed in gastric cancer group and intestinal metaplasia group,especially intestinal type gastric cancer,highly and moderately differentiated gastric cancer,type Ⅰ and type Ⅱ intestinal metaplasia(P<0.05).The expression of MUC5AC was high in control group and low in gastric cancer group and intestinal metaplasia group,especially in intestinal type gastric cancer,type Ⅰ and type Ⅲ intestinal metaplasia(P<0.05).Gastric cancer and intestinal metaplasia differentiation were negatively correlated with MEX3A and MUC5AC expression,but positively correlated with CDX2 and MUC2 expression(P<0.05).MEX3A was negatively correlated with the expression of CDX2 and MUC2,and positively correlated with the expression of MUC5AC in gastric cancer(P<0.05).MEX3A was negatively correlated with the expression of CDX2 and MUC2 in intestinal metaplasia(P<0.05),while CDX2 was positively correlated with the expression of MUC2(P<0.05).Conclusion MEX3A is negatively correlated with gastric cancer and intestinal metaplasia differentiation.Gastric cancer is characterized by high MEX3A expression and low CDX2 and MUC2 expression.

Inflammatory bowel disease (IBD) is a formidable disease due to its complex pathogenesis. Macrophages, as a major immune cell population in IBD, are crucial for gut homeostasis. However, it is still unveiled how macrophages modulate IBD. Here, we found that LIM domain only 7 (LMO7) was downregulated in pro-inflammatory macrophages, and that LMO7 directly degraded 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) through K48-mediated ubiquitination in macrophages. As an enzyme that regulates glycolysis, PFKFB3 degradation led to the glycolytic process inhibition in macrophages, which in turn inhibited macrophage activation and ultimately attenuated murine colitis. Moreover, we demonstrated that PFKFB3 was required for histone demethylase Jumonji domain-containing protein 3 (JMJD3) expression, thereby inhibiting the protein level of trimethylation of histone H3 on lysine 27 (H3K27me3). Overall, our results indicated the LMO7/PFKFB3/JMJD3 axis is essential for modulating macrophage function and IBD pathogenesis. Targeting LMO7 or macrophage metabolism could potentially be an effective strategy for treating inflammatory diseases.

OBJECTIVE: To investigate the effect of Bmi-1 gene silence on the proliferation ability of K562 cells in vitro and in vivo, and to explore the relation of molecular mechanism between proliferation ability of K562 cells in vitro and in vivo with PTEN/pAKT signaling pathway. METHODS: The Bmi-1 small interference RNA (siRNA) sequences were transfected into K562 cells for decreasing Bmi-1 expression. The effect of Bmi-1 siRNA on the proliferation of K562 cells in vitro and in vivo was detected by MTT method and colony-forming test, the effect of Bmi-1 siRNA on the tumorogenicity of K562 cells was observed by subcutaneous inoculation of K562 cells, LY294002 and Bpv treated K562 cells in nude mice, the expression of Bmi-1, PTEN and pAKT proteins were detected by Western blot. RESULTS: The Bmi-1 siRNA could inhibit the proliferation activity, colony-forming and tumor-forming abilities of K562 cells. After the silence of Bmi-1 gene, the PTEN expression in Bmi-1 gene-silenced group was significantly enhanced. While the pAKT expression in Bmi-1 gene-silenced group was significantly reduced; after the K562 cells were treated with LY294002 (an inhibitor of pAKT), the pAKT expression colony-forming and tumor forming abilities were reduced in comparison with untreated K562 cells; after the K562-S1 cells were treated with Bpv (an inhibitor of PTEN), the PTEN expression decreased, while the pAKT expression, colony forming and tumor-forming abilities were restored. CONCLUSION The Bmi-1 gene possibly involves in regulation of K562 proliferation in vivo and in vitro, the effect of PTEN/pAKT signaling pathway maybe one of molecular mechanisms mediating this regulation.
Animals ; Apoptosis ; Cell Proliferation ; Humans ; K562 Cells ; Leukemia ; Mice ; Mice, Nude ; PTEN Phosphohydrolase ; Polycomb Repressive Complex 1 ; Proto-Oncogene Proteins c-akt ; RNA, Small Interfering ; Signal Transduction