1. A network pharmacology-based approach to explore mechanism of kaempferol-7 -O -neohesperidoside against prostate cancer
Qiu-Ping ZHANG ; Zhi-Ping CHENG ; Wei XUE ; Qiao-Feng LI ; Hong-Wei GUO ; Qiu-Ping ZHANG ; Jie-Jun FU ; Hong-Wei GUO
Chinese Pharmacological Bulletin 2024;40(1):146-154
Aim To explore the effect of kaempferol-7- 0-neohesperidoside (K70N) against prostate cancer (PCa) and the underlying mechanism. Methods The effect of K70N on the proliferation of PCa cell lines PC3, DU145, C4-2 and LNCaP was detected using CCK8 assay. The effect of K70N on migration ability of DU145 cells was determined by wound healing assay. The targets of K70N and PCa were screened from SuperPred and other databases. The common targets both related to K70N and PCa were obtained from the Venny online platform, a protein-protein interaction network (PPI) was constructed by the String and Cyto- scape. Meanwhile, the GO and KEGG functional enrichment were analyzed by David database. Then, a "drug-target-disease-pathway" network model was constructed. Cell cycle of PCa cells treated with K70N was analyzed by flow cytometry. The expressions of cycle-associated proteins including Skp2, p27 and p21 protein were detected by Western blot. Molecular docking between Skp2 and K70N was conducted by Sybyl X2. 0. Results K70N significantly inhibited the proliferation and migration of PCa cells. A total number of 34 drug-disease intersection targets were screened. The String results showed that Skp2 and p27, among the common targets, were the key targets of K70N for PCa treatment. Furthermore, GO and KEGG functional en-richment indicated that the mechanism was mainly related to the cell cycle. Flow cytometry showed that K70N treatment induced cell cycle arrest at the S phase. Compared with the control group, the protein expression level of Skp2 was significantly down-regulated, while the protein expression levels of p27 and p21 were up-regulated. The network molecular docking indicated that the ligand K70N had a good binding ability with the receptor Skp2. Conclusions K70N could inhibit the proliferation and migration of PCa cells, block the cell cycle in the S phase, which may be related to the regulation of cell cycle through the Skp2- p27/p21 signaling pathway.
2.Biological Basis of Premature Ejaculation Based on Theory of "Brain-heart-kidney-semen Chamber" Axis
Dongyue MA ; Anmin WANG ; Jiutian YANG ; Dicheng LUO ; Ziwei ZHAO ; Jun GUO ; Fu WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):203-209
The theory of "brain-heart-kidney-semen chamber" axis is proposed based on the basic theories of traditional Chinese medicine, the modern physiological characteristics of men's diseases, and clinical practice. According to this theory, dysfunctions of the brain, heart, kidney, and semen chamber are the core mechanisms for the occurrence of premature ejaculation, and the loss of control of the opening and closing of the seminal orifices due to the dysfunction of the semen chamber is the final link in the occurrence of premature ejaculation. The treatment of premature ejaculation based on the theory of "brain-heart-kidney-essence chamber" axis highlights the overall regulation of the Zang-fu organs involved in the disease, while focusing on the simultaneous treatment of the mind and body. By exploring the biological basis of the "brain-heart-kidney-essence chamber" axis and premature ejaculation, we propose that the biological basis of premature ejaculation and the axis is mainly related to the function decline of the local brain area, neuromodulation malfunction, central neurotransmitter imbalance, endocrine disorders, and enhanced sensory afferents of the penis. This study aims at providing a new approach for the prevention and treatment of premature ejaculation by traditional Chinese medicine and a scientific basis for the development of more effective therapeutic methods.
3.Stability study of umbilical cord mesenchymal stem cells formulation in large-scale production
Wang-long CHU ; Tong-jing LI ; Yan SHANGGUAN ; Fang-tao HE ; Jian-fu WU ; Xiu-ping ZENG ; Tao GUO ; Qing-fang WANG ; Fen ZHANG ; Zhen-zhong ZHONG ; Xiao LIANG ; Jun-yuan HU ; Mu-yun LIU
Acta Pharmaceutica Sinica 2024;59(3):743-750
Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.
4.Characteristics of myocardial injury in patients with acute myocardial infarction complicated with pleural effusion and its influence on long-term prognosis
Guangren GAO ; Lianrong FENG ; Jinguo FU ; Run GUO ; Heping NIU ; Fengpeng LI ; Qianyu ZHANG ; Jun ZHANG
Tianjin Medical Journal 2024;52(2):197-201
Objective To explore the characteristics of myocardial injury in patients with acute myocardial infarction(AMI)complicated by pleural effusion and its effect on long-term prognosis.Methods It was a prospective single-center study.Patients with AMI who were admitted to hospital within 15 days from symptom onset and performed echocardiography and cardiac magnetic resonance imaging(CMR)during hospitalization were consecutively enrolled and assigned to the with-pleural effusion group and the without-pleural effusion group according to the echocardiography result.Baseline data,cardiac magnetic resonance myocardial injury index and echocardiography characteristics were compared between the two groups.The occurrence of major adverse cardiovascular and cerebrovascular events(MACCE)was recorded through outpatient follow-up and telephone follow-up,including all-cause death,re-infarction,revascularization,rehospitalization for congestive heart failure and stroke.Cox regression analysis was performed to analyze influencing factors of all-cause death.Results Among 211 patients,31(14.7%)patients had pleural effusion and 180(85.3%)had no pleural effusion.Compared with the group without pleural effusion,the left ventricular end-diastolic diameter was larger,and left ventricular ejection fraction assessed by echocardiography was lower in the group with pleural effusion(P<0.05).There were no significant differences in infarct size,left ventricular end-diastolic volume,left ventricular end-systolic volume,left ventricular ejection fraction and the presence of microvascular obstruction and intramyocardial hemorrhage between the two groups in CMR(all P>0.05).At a median follow-up of 31 months,MACCE occurred in 43(20.4%)patients,and there was no significant difference between the two groups(χ2=3.160,P=0.075).Six cases(2.8%)had all-cause death.The incidence of all-cause death was higher in the group with pleural effusion than that in the group without pleural effusion(9.7%vs.1.7%,P<0.05).There was no significant difference in the incidence of other adverse events between the two groups(P>0.05).Multivariate Cox regression analysis showed that advanced age and presence of pleural effusion were independent risk factors of all-cause death during follow-up.Conclusion Patients with AMI combined with pleural effusion have more severe myocardial injury and higher all-cause mortality.
5.Current status and prospects of postoperative adjuvant therapy for hepatocellular carcinoma
Yongyi ZENG ; Jun FU ; Kongying LIN ; Luobin GUO
Chinese Journal of Digestive Surgery 2024;23(2):221-227
The high recurrence and metastasis rate of hepatocellular carcinoma (HCC) in patients after hepatectomy significantly impact the prognosis. Exploring effective strategies and indications of postoperative adjuvant therapy for HCC is of great clinical significance in reducing postoperative recurrence rate and improving long-term survival. Traditional local treatment modalities, including transcatheter arterial chemoembolization, hepatic artery infusion chemotherapy, and radiotherapy, continue to play a crucial role in postoperative adjuvant therapy. Recently, the emergence of novel systemic therapy agents, including molecular targeted drugs and immune checkpoint inhibitors, has transformed the landscape of postoperative adjuvant therapy, making the selection of adjuvant therapy more intricate and diverse. The author combines the latest progress in adjuvant therapy to explore the strategies and challenges of postoperative adjuvant therapy for HCC.
6.Exploring the treatment based on syndrome differentiation of male lower urinary tract symptoms based on the theory of "zang-fu extraordinary connection"
Jiutian YANG ; Jun GUO ; Qinghe GAO ; Ming ZHAO ; Shuang WU ; Dongyue MA ; Anmin WANG ; Fu WANG
Journal of Beijing University of Traditional Chinese Medicine 2024;47(3):302-306
Male lower urinary tract symptoms is a collective term for a group of symptoms associated with lower urinary tract disorders characterized by frequent urination, urgent urination, and difficulty of urination, of which the common causes are benign prostatic hyperplasia or overactive bladder. With the aging of the global population, the incidence of male lower urinary tract symptoms is increasing year by year. Based on the theoretical connotation of " zang-fu extraordinary connection", the relationship between the lungs and the bladder, the spleen and the small intestine, and the kidneys and the sanjiao with the formation of male lower urinary tract symptoms is explained from three perspectives. It is believed that lung qi depression and closure, disturbance of qi transformation in bladder, and insufficient spleen transport occur, the small intestine is dysfunctional, kidney yang is exhausted, and obstruction of the sanjiao waterway are the basic pathogenesis of male lower urinary tract symptoms. It is emphasized that the location of the disease should be identified. If it is related to the lungs and the bladder, then the disease should be treated by lifting the pot to lift the lid and diffusing the lung qi to benefit the bladder with Wuling Powder plus perilla leaf and bitter apricot seed; if it is related to the spleen and the small intestines, then the disease should be treated by raising the clear and directing the turbid downward and improving the spleen qi in order to support the small intestines with Shenling Baizhu Powder; if it is related to the kidneys and the sanjiao, then the disease should be treated by seeking the yang within the yin and warming and tonifying the kidney qi in order to dredge up the sanjiao with Bawei Shenqi Pill. According to the patient's condition, treatment can be combined with acupuncture, exercise, and other therapies. This paper can provide reference for clinical treatment of male lower urinary tract symptoms.
7.Exploring the traditional Chinese medicine differentiation and treatment of male infertility based on the theory of"maintaining with the sweet and restoring the body fluids"
Hongyuan CHANG ; Hao WANG ; Anmin WANG ; Dongyue MA ; Ziwei ZHAO ; Dicheng LUO ; Jun GUO ; Fu WANG
Journal of Beijing University of Traditional Chinese Medicine 2024;47(7):948-952
Male infertility,a common condition in andrology,falls under the category of"no son"in traditional Chinese medicine(TCM).Unhealthy eating habits and excessive sexual activity,prevalent due to improved living standards,have contributed to the increasing incidence of male infertility.YE Tianshi proposed the theory of"maintaining with the sweet and restoring the body fluids",which emphasizes the importance of ample body fluid for the nourishment of the male essence chamber.Sufficient body fluid is crucial for normal sperm generation.In TCM,the primary pathogenesis of male infertility involves the loss of body fluids and insufficiency of yin essence.Sweet Chinese herbal medicinal is recommended as it nourishes yin,enriches essence,and replenishes male reproductive essence without producing phlegm and dampness.Therefore,when treating male infertility,attention should be given to the use of sweet Chinese herbal medicinal,adhering to the principle of"abundant body fluids nourish kidney yin,and abundant kidney yin supports semen production".Therapies such as purging fire to preserve body fluids with Zengye Decoction,nourishing yin to enrich essence with Guilu Erxian Decoction,benefiting qi to promote fluid production with Buzhong Yiqi Decoction,and warming yang and transporting fluids with Xianfu Shezi Decoction should be considered.Medication and dosage adjustments should be made based on the specific etiology,pathology,and related symptoms to improve the quality of male sperm and enhance the chances of conception.
8.Clinical trial of Morinda officinalis oligosaccharides in the continuation treatment of adults with mild and moderate depression
Shu-Zhe ZHOU ; Zu-Cheng HAN ; Xiu-Zhen WANG ; Yan-Qing CHEN ; Ya-Ling HU ; Xue-Qin YU ; Bin-Hong WANG ; Guo-Zhen FAN ; Hong SANG ; Ying HAI ; Zhi-Jie JIA ; Zhan-Min WANG ; Yan WEI ; Jian-Guo ZHU ; Xue-Qin SONG ; Zhi-Dong LIU ; Li KUANG ; Hong-Ming WANG ; Feng TIAN ; Yu-Xin LI ; Ling ZHANG ; Hai LIN ; Bin WU ; Chao-Ying WANG ; Chang LIU ; Jia-Fan SUN ; Shao-Xiao YAN ; Jun LIU ; Shou-Fu XIE ; Mao-Sheng FANG ; Wei-Feng MI ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(6):815-819
Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P<0.05).After continuation treatment,the remission rate was 54.59%(202 cases/370 cases),and the recurrence rate was 6.49%(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35%(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.
9.Development of a High-throughput Sequencing Platform for Detection of Viral Encephalitis Pathogens Based on Amplicon Sequencing
Li Ya ZHANG ; Zhe Wen SU ; Chen Rui WANG ; Yan LI ; Feng Jun ZHANG ; Hui Sheng LIU ; He Dan HU ; Xiao Chong XU ; Yu Jia YIN ; Kai Qi YIN ; Ying HE ; Fan LI ; Hong Shi FU ; Kai NIE ; Dong Guo LIANG ; Yong TAO ; Tao Song XU ; Feng Chao MA ; Yu Huan WANG
Biomedical and Environmental Sciences 2024;37(3):294-302
Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.
10.A Prognostic Model Based on Colony Stimulating Factors-related Genes in Triple-negative Breast Cancer
Yu-Xuan GUO ; Zhi-Yu WANG ; Pei-Yao XIAO ; Chan-Juan ZHENG ; Shu-Jun FU ; Guang-Chun HE ; Jun LONG ; Jie WANG ; Xi-Yun DENG ; Yi-An WANG
Progress in Biochemistry and Biophysics 2024;51(10):2741-2756
ObjectiveTriple-negative breast cancer (TNBC) is the breast cancer subtype with the worst prognosis, and lacks effective therapeutic targets. Colony stimulating factors (CSFs) are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells, playing an important role in the malignant progression of TNBC. This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes (CRGs), and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy. MethodsWe downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database. Through LASSO Cox regression analysis, we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score (CRRS). We further analyzed the correlation between CRRS and patient prognosis, clinical features, tumor microenvironment (TME) in both high-risk and low-risk groups, and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy. ResultsWe identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model. Kaplan-Meier survival curves, time-dependent receiver operating characteristic curves, and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival, and the predictive ability of CRRS prognostic model was further validated using the GEO dataset. Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients. Moreover, patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil, ipatasertib, and paclitaxel. ConclusionWe have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs, which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment. Moreover, the key genes within this model may represent potential molecular targets for future therapies of TNBC.

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