1.Mechanism of treatment of Tibet yak-origin Salmonella infections by Tibetan medicine Terminalia Chebula via Bax/Bcl-2 and PTGS2/SLC3A2 pathway was analyzed based on network pharmacology and experimental validation
Dengyu LI ; Kaiqin ZHANG ; Xiaofeng XUE ; Zhanchun BAI ; La YANG ; Shaohui WANG ; Jingjing QI ; Sizhu SUOLANG
Chinese Journal of Veterinary Science 2024;44(9):2040-2049
In order to understand the potential target and related mechanism of action of Termina-lia Chebula treatment,network pharmacology and molecular docking methods were used in this experiment,and the challenge test of Salmonella from yak was performed.The active ingredients and potential targets of Terminalia Chebula were screened through HERB cluster identification database,TCMSP database and SwissTargetPrediction web page tool,and"gastroenteritis"was searched through OMIM and GeneCards database.Cytoscape and STRING databases were used to construct the Terminalia Chebula PPI network to screen out key targets,the intersection targets between Terminalia Chebula and enteritis were obtained through Venny platform,and gene ontol-ogy(GO)and Kyoto encyclopedia database of genes and genomics(KEGG)were enriched through DAVID database.The core target of screening was verified by molecular docking.After that,the gastrointestinal inflammation model of mice was established,the pathological changes of gastroin-testinal tract were observed,and the effect of Terminalia Chebula on the target protein was veri-fied by Western blot test.The results showed that:after analyzing and sorting out 8 main active in-gredients of Terminalia Chebula,118 targets of Terminalia Chebula were screened,11 161 targets of gastroenteritis and 100 targets of intersection were obtained;the core targets of PTGS2,CASP3,SLC3A2,Bax,Bcl-2 and TP53 of Terminalia Chebula and enteritis were obtained through PPI network.GO and KEGG enrichment analysis collected 337 items and 138 items,respectively,mainly related to chemokine pathway,PI3K-Akt signaling pathway,apoptosis related pathway,i-ron ion transport related pathway,NF-κB signaling pathway,etc.The results of molecular docking showed that chebulidic acid,the first active component of chebulidic acid,can bind to Bax,Bcl-2,PTGS2 and SLC3A2 through hydrogen bonding,hydrophobic action,π-π packing force and other intermolecular forces.The pathological tissue sections showed that Terminalia Chebula could sig-nificantly recover gastrointestinal tissue injury.Western blot test results showed that Terminalia Chebula can regulate the process of apoptosis and iron death through Bax/Bcl-2 and PTGS2/SLC3A2 pathways to achieve the effect of treating intestinal inflammatory damage.The results showed that Terminalia Chebula can regulate the occurrence and development of enteritis by regu-lating apoptosis and iron death through Bax/Bcl-2 and PTGS2/SLC3A2 pathways.Terminalia Chebula has the characteristics of multi-target and multi-pathway in the treatment of enteritis.
2.Immunomodulatory effect of pachymaran on cyclosporine A (CsA)-induced lung injury in mice
CHEN Kaiqin ; WEI Ke ; YE Chun ; ZHAO Tianhao ; ZHANG Bo ; XIAO Rong ; LU Fangguo
Digital Chinese Medicine 2022;5(2):222-232
Objective To investigate the immunomodulatory effect of pachymaran on cyclosporine A (CsA)-induced lung injury in mice. Methods (i) Fifty male BALB/c mice were randomly divided into five groups (10 mice in each group): normal control (NC) group, 30, 45, and 60 mg/kg CsA groups, and lipopolysaccharide (LPS) group. Except for the NC group, other groups underwent CsA modeling. The NC group was treated with phosphate-buffered saline (PBS), the LPS group with 10 mg/kg LPS eight hours before mice euthanized, and the 30, 45, and 60 mg/kg CsA groups with corresponding doses of CsA for seven consecutive days. After treatment, the body and organ mass of each group were weighed, and the lung, thymus, and spleen indexes were calculated. Hematoxylin-Eosin (HE) staining was performed to observe histopathological changes in the lungs of the mice. The protein expression levels of interleukin (IL)-2 and IL-1β in the blood were detected using enzyme-linked immunosorbent assay (ELISA), and those of surfactant protein D (SP-D), IL-2, and IL-6 in lung tissues were detected by immunohistochemistry (IHC). The mRNA expression levels of SP-D, IL-1β, IL-6, and myeloperoxidase (MPO) in the lung tissues were detected by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). (ii) Another 60 BALB/c mice were divided into six groups (10 mice in each group) : NC group, model control (MC) group, 50, 100, and 200 mg/kg pachymaran groups, and polyinosinic-polycytidylic acid [poly(I:C)] group. Except for the NC group, other groups underwent 45 mg/kg CsA modeling. The NC and MC groups were treated with distilled water, the pachymaran groups with corresponding doses pachymaran, and the poly(I:C) group with 0.1 mg/kg poly(I:C) for seven days.The mice were euthanized to obtain tissues and serum for detection. Detection methods were identical to those described in (i) above. Results (i) CsA (30 mg/kg) increased the lung index of mice (P < 0.001), and decreased the spleen index (P < 0.01), thymus index (P < 0.05), and the serum level of IL-2 (P < 0.05). CsA (45 mg/kg) decreased the spleen, thymus indexes, and the serum level of IL-2 (P < 0.01) in mice, and increased the serum level of IL-1β (P < 0.05) and the protein level of lung SP-D (P <0.001). CsA (60 mg/kg) increased the lung index of mice (P < 0.01), the serum level of IL-1β (P < 0.05), the protein level of lung SP-D (P < 0.01), and the mRNA levels of lung MPO and SP-D ( P < 0.05), and decreased the thymus index of mice (P < 0.01). HE staining showed that 30, 45, and 60 mg/kg CsA, and LPS caused pathological changes in the lung tissue of mice. (ii) After pachymaran intervention in MC mice, the spleen and thymus indexes (P < 0.05) were increased in the 100 and 200 mg/kg pachymaran groups, and the lung index was decreased (P < 0.05). Moreover, 50 mg/kg pachymaran increased the thymus index (P < 0.05) and decreased the lung index (P < 0.01) in MC group. Pachymaran (50, 100, and 200 mg/kg) improved lung tissue injury, reduced the serum level of IL-1β (P < 0.001), and the mRNA levels of MPO and SP-D in lung tissues (P < 0.05) of mice. Pachymaran (100 mg/kg) increased the protein level of lung IL-2 (P < 0.01), decreased the protein level of lung SP-D (P < 0.01), and the mRNA level of IL-1β (P < 0.001) in the lung tissues of mice. Pachymaran (200 mg/kg) increased the serum level of IL-2 (P < 0.01) and lung IL-6 of mice (P < 0.05). Pachymaran (50 and 200 mg/kg) increased the mRNA level of IL-6 in the lung tissues of mice (P < 0.05). Conclusion While the immune function of mice was suppressed by CsA, the lung tissue was also damaged. Pachymaran can improve the immunosuppression induced by CsA and improve the lung tissue injury in immunosuppressed mice.
3.The status and progress of morning glory syndrome
Kaiqin SHE ; Qi ZHANG ; Peiquan ZHAO
Chinese Journal of Ocular Fundus Diseases 2017;33(5):557-560
Morning glory syndrome (MGS) is a congenital optic disc anomaly. The characteristic ophthalmoscopic findings consist of a generally enlarged, funnel-shaped and excavated optic disc, surrounded by an elevated annulus of chorioretinal pigment disturbance, with a central glial tuft, multiple narrow branches of retina vessels radiating from the disc. There are peripheral non-perfusion retinal areas in most cases. The pathogenesis of MGS remains unclear. MGS might be associated with many ocular and systemic abnormalities, involving facial, central nervous, cerebrovascular and endocrine systems. Persistent hyperplastic primary vitreous and retinal detachments (RD) are the most common ocular complications of MGS. The mechanism RD in MGS is unclear. Vitrectomy with long-acting gas or silicone tamponade and photocoagulation around the breaks or the enlarged disc might be efficient for rhegmatogenous RD of MGS. Early diagnosis is crucial for recognition and treatment of the ocular and systemic complications, and maintenance of the visual function.
4.Effects of UGT146 and UGT1A9 Gene Polymorphisms on Blood Concentration of Valproic Acid in Han Epileptic Patients
Xueyu LIN ; Yanqing ZHANG ; Pengfeng LIN ; Kaiqin ZHOU ; Hui HONG ; Yan FEI
China Pharmacy 2017;28(8):1013-1017
OBJECTIVE:To investigate the effects of UGT1A6 and UGT1A9 gene polymorphisms on blood concentration of valproic acid in Han epileptic patients.METHODS:Totally 107 Chinese Han epileptic patients were selected from outpatient department of our hospital during Jan.2014-Apr.2015.They were given valproic acid monotherapy treatment for 3 months to 6 years.The steady state concentration ofvalproic acid was detected by EMIT.UGT1A6 (rs2070959,rs6759892) and UGT1A9 (rs13418420,rs2741045,rs2741049,rs6731242,rs72551330) genotypes were detected by MALDI-TOF-MS.The correlation of gene polymorphism with con centration dose ratios (CDR) of valproic acid was investigated.RESULTS:UGT1A9 rs72551330 mutation had not been detected,and the frequency of genotypes in other 6 sites were all in line with Hardy-Weinberg balance (P>0.05).The CDR of valproic acid in pa tients with UGT1A6 rs2070959,rs6759892 mutation (AG+GG or TG+GG type) were significantly lower than those with wild homozy gote (AA or TT type),with statistical significance (P< 0.05).There was no statistical significance in CDR of valproic acid among patients with UGT1A9 rs13418420,rs2741045,rs2741049 and rs6731242 wild homozygote and mutation (P>0.05).CONCLUSIONS:UGT1A6 rs2070959,rs6759892 gene polymorphisms of Han epileptic patients are associated with blood concentration of valproic acid,and the patients with UGT1A6 rs2070959,rs6759892 mutation need more dose ofvalproic acid.
5.The effect of the interval between neoadjuvant therapy and surgery on downstaging for rectal cancer
Kaiqin PENG ; Yongsheng SHAO ; Yingtian ZHANG ; Chiding HU ; Yang YU ; Wenliang WU
International Journal of Surgery 2011;38(8):511-514
Objective To discuss the effect of the interval between neoadjuvant therapy and surgery on downstaging for local advanced rectal cancer.Method s From May 2003 to December 2008 as earlier period,32 patients with clinical stage T3 or T4 rectal cancer received neoadjuvant therapy followed by surgery after 4 -6 weeks.From January 2009 to December 2010 as later period,21 patients with clinical stage T3 or T4 rectal cancer received neoadjuvant therapy followed by surgery after 8 weeks.Dworak classification,TNM stage and clinical outcome after surgery were compared between two group paitents.Results All patients with local advanced rectal cancer received R0 resection.No surgical complications and mortality were observed in all cases.Pathological results showed that 0 and 2 cases were Dworak classification Ⅳ,5 cases were Dworak classification Ⅲ,3 and 6 cases were Dworak classification Ⅱ and 24 and 8 cases were Dworak classification Ⅰ in earlier period and later period,respectively (x2 = 9.109,P = 0.028).The postoperative staging showed that 6 and 13 cases were ypT1N0M0,22 and 6 cases were ypT2N0M0,1 case was ypT3 N0M0,3 and 1 cases were ypT3N1 M0,respectively (x2 = 10.909,P = 0.012).There were 65.6% or 81.0% cases reserved anus in earlier period and later period,respectively(x2 = 1.468,P = 0.226).Conclusions The neoadjuvant therapy followed by surgery after 8 weeks is associated with a more significant downstaging effect for local advanced rectal cancer.However,the effect of an extended interval between neoadjuvant therapy and surgery on clinical outcome still needs further investigation.
6.Advances of the Relationship Between Tumor Suppressor Gene DPC4 and Pancreatic Carcinoma
Chinese Journal of Bases and Clinics in General Surgery 2003;0(04):-
Objective To investigate the relationship between tumor suppressor gene DPC4 and the development and prognosis of pancreatic carcinoma. Methods Relevant literatures of recent years were reviewed. Results DPC4 was located on chromosome 18. Its product was Smad 4 protein. Smad 4 protein was the central component of the transforming growth factor-beta signaling pathway, and all the biological effect was the results of interaction of Smad 4 and different Smads. The gene was deleted or inactive in about 50% of pancreatic carcinomas. The deletion of DPC4 had a great relation to the development and prognosis of pancreatic carcinoma. Conclusion The alteration of tumor suppressor gene DPC4 is connected with the development and prognosis of pancreatic carcinoma. However, this research should be further studied.
7.Prognostic significance of the number of lymph nodes removed surgically in patients with colorectal cancer
Rong LI ; Shaomin GONG ; Kaiqin PENG ; Lijiang LIU ; Yingtian ZHANG
Chinese Journal of General Surgery 2001;0(10):-
or ≤50 in each patient. 5-year survival curves were estimated with the Kaplan-Meier method and compared by the log-rank test. ResultsWT5”BZ Analysis revealed that among node-negative patients, the 5-yerar's survival rate was 23% higher in patients with more than 50 nodes removed than those with less than 50. For node-positive patients, the difference of 5-year′s survival rate between the related two subgroups reached 36%.WT5”HZConclusion The number of lymph node resected has great impact on the long term survival of patients with colorectal cancer.
8.Intracavitary irradiation therapy for unresectable advanced for hilar cholangiocarcinoma
Zhuoyong QYAN ; Kaiqin PENG ; Yingtian ZHANG
Journal of Clinical Surgery 2001;0(04):-
Objective In this study we reported our experiences for patients with unresectable advanced hilar cholangiocarcinoma by intracavitary irradiation therapy and discussed some problemsin practice.Method 15 cases with unresectable advanced hilar cholangiocarcinoma were treated with laparotomy and operative dilatation of malignant stenosis and cathetenizing and then followed by intracavitary irradiation therapy.Result 15 cases treated by intracavitary irradiation therapy diedfrom liver function failure with biliary cirrhosis 3~18 months (average 8 months) later. None of the case died from cancer dissemination. Conclusion The patients with advanced holar cholangiocarcinoma could well tolerant of the intracavitary irradiation therapy, but they deteriolated from biliary cirrhosis about 8 months later,not from tumor dissemination.
9.Effects of 7.5% hypertonic saline on fluid balance after elective major abdominal surgery
Yongsheng SHAO ; Yingtian ZHANG ; Kaiqin PENG ; Zhuoyong QUAN ; Shaomin GONG ;
Chinese Journal of General Surgery 2000;0(12):-
Objective To investigate the effects of 7 5% hypertonic saline (HS) on fluid balance after elective major abdominal surgery Methods Twenty two patients undergoing elective major abdominal surgery were assigned to receive either Ringer lactate solution followed by 4 ml/kg of 7 5% HS (study group, n =11) or Ringer lactate solution (control group, n =11) during the early postoperative period in ICU We compared fluid infusion volumes and urine outputs, fluid balance, and body weight change between the 2 groups Results Urine outputs in the operative day and the first postoperative day in study group were significantly more than in control group [(2?650?531)ml vs (2?046?572)ml, t =2 551?7, P
10.The relationship between the resection extent and number of lymph node dissection and the effect of metastatic lymph node number on the prognosis of proximal gastric cancer
Wen LIU ; Kaiqin PENG ; Shaomin GONG ; Lijiang LIU ; Yingtian ZHANG
Chinese Journal of General Surgery 2000;0(12):-
Objective To study the relation between the surgical extent and number of lymph node dissection and the effect of metastatic lymph node number on the prognosis of proximal gastric cancer. Method Thirty-one patients with proximal gastric cancer underwent D_2 or D_3 operation, and lymph node were harvested from specimen. The number of lymph node dissection in proximal gastrectomy was compared with that in total gastrectomy. Results A total of 1971 lymph nodes were obtained from the 31 specimens, the mean was 63 per case. There were 57 lymph nodes per case for patients with proximal gastrectomy and 71 per case with total gastrectomy,64 per case with left half pancreaticosplenectomy and 63 per case with splenectomy. According to the new 5th N stage system, the 5 year survival of N_1,N_2,N_3 were 36%, 11%, and 0 respectively. Conclusion Along with the wide invasion of the carcinoma wide resection with extended lymph node dissection is mandatory, reserved left half of the pancreas has no influence on the number of harvested lymphnode, the new quantitative N staging is superior to the old in predicting the prognosis.

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