Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 19 de 19
Filter
1.
J Biomed Res ; 38(1): 76-86, 2023 Dec 04.
Article in English | MEDLINE | ID: mdl-38044669

ABSTRACT

The present study aimed to dynamically observe the segmental and global myocardial movements of the left ventricle during coronary artery bypass grafting by transesophageal speckle-tracking echocardiography, and to assess the effect of sevoflurane on cardiac function. Sixty-four patients scheduled for the off-pump coronary artery bypass grafting were randomly divided into a sevoflurane-based anesthesia (AS) group and a propofol-based total intravenous anesthesia (AA) group. The AS group demonstrated a higher absolute value of left ventricular global longitudinal strain than that of the AA group at both T 1 (after harvesting all grafts and before coronary anastomosis) and T 2 (30 min after completing all coronary anastomoses) ( P < 0.05). Moreover, strain improvement in the segment with the highest preoperative strain was significantly reduced in the AS group, compared with the AA group at both T 1 and T 2 ( P < 0.01). The flow of the left internal mammary artery-left anterior descending artery graft was superior, and the postoperative concentration of troponin T decreased rapidly in the AS group, compared with the AA group ( P < 0.05). Compared with total intravenous anesthesia, sevoflurane resulted in a significantly higher global longitudinal strain, stroke volume, and cardiac output. Sevoflurane also led to an amelioration in the condition of the arterial graft. Furthermore, sevoflurane significantly reduced strain improvement in the segmental myocardium with a high preoperative strain value. The findings need to be replicated in larger studies.

2.
Heliyon ; 9(10): e20405, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37780755

ABSTRACT

Anesthesiologists are often faced with patients combined with a series of organ injuries, such as acute lung injury, myocardial ischemia-reperfusion injury, and neurodegenerative diseases. With the in-depth study of these diseases, we are more aware of the choice and rational use of anesthetics for the prognosis of these patients. Ferroptosis is a new type of programmed cell death. This unique pattern of cell death, driven by an imbalance between oxides and antioxidants, is regulated by multiple cellular metabolic events, including redox homeostasis, iron handling, mitochondrial activity, and lipids peroxidation. Numerous studies confirmed that anesthetics modulate ferroptosis by interfering its machineries such as cystine-import-glutathione-glutathione peroxidase 4 axis, Heme oxygenase 1, nuclear factor erythroid 2-related factor 2, and iron homeostasis system. In this literature review, we systemically illustrated possible involvement of ferroptosis in effects of anesthetics and adjuvant drugs on multiple organ diseases, hoping our work may serve as a basis for further studies on regulating ferroptosis through anesthetics related pharmacological modulation and promoting the rational use of anesthetics.

3.
J Sci Food Agric ; 103(10): 5145-5155, 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-36988338

ABSTRACT

BACKGROUND: Tea polysaccharide conjugate (TPC) is a naturally occurring active substance that is extracted from tea. Owing to its benefits in enhancing human immunity and antioxidant effects, TPC is widely used in culinary products. The binding mode of polysaccharides and proteins in TPC, however, has not been well studied; it may be closely related to their functional properties, especially emulsification. RESULTS: The molecular weights and monosaccharide compositions of TPC were determined by ion chromatography and high-performance gel permeation chromatography. Although the functional groups of polysaccharides and proteins were confirmed by infrared spectroscopy, the presence of proteins could not be detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis and ultraviolet spectroscopy. It was hypothesized that the hydrophobic groups of the proteins in TPC were wrapped by polysaccharide chains, thus making the proteins undetectable. The rheology and interfacial protein adsorption results show that TPC forms a viscoelastic film at the oil-water interface to prevent the aggregation of oil droplets, thereby enhancing the stability of the emulsion. Based on these structural and emulsifying properties of TPC, the binding mode of polysaccharides and proteins along with their phase behavior at the oil-water interface of the emulsion was speculated. CONCLUSION: In TPC, the hydrophilic groups of the proteins are linked to polysaccharides by covalent interactions, where the hydrophobic groups are wrapped with the polysaccharide chains with the help of hydrophobic forces to form a hydrophobic core. The unique binding of polysaccharides and proteins in TPC enhances its amphiphilic properties, which can be effectively distributed at the oil-water interface and form stable emulsions. © 2023 Society of Chemical Industry.


Subject(s)
Polysaccharides , Tea , Humans , Emulsions/chemistry , Polysaccharides/chemistry , Adsorption , Tea/chemistry , Water/chemistry
4.
J Vasc Access ; 24(3): 436-442, 2023 May.
Article in English | MEDLINE | ID: mdl-34387514

ABSTRACT

BACKGROUND: Ultrasound-guided axillary vein (AxV) cannulation has been described as an effective alternative to internal jugular vein cannulation in adult cardiac surgical patients. However, the learning curve for this technique has not yet been addressed. This study aimed to determine the number of cases required to achieve proficiency in performing AxV cannulation among novice anesthesiologists. METHODS: This prospective study included the first 60 patients who underwent ultrasound-guided AxV cannulation performed by a single third-year resident who was trained in adult cardiac anesthesia. This study investigated the number of cases required to gain technical proficiency by applying cumulative sum analysis on the learning curve (LC-CUSUM) of ultrasound-guided AxV cannulation. RESULTS: Based on the assessment of the CUSUM plots, a descending inflection point for decreasing the overall procedural time for AxV cannulation was observed after patient 29. Regarding the procedural outcomes, comparing the early-experience group with the late-experience group (29 vs 31 cases), the former group had longer operating time (1526 s vs 1120 s, p < 0.001) and identification time (110 s vs 92 s, p < 0.001) and lower first-attempt success rate (8, 27.6% vs 30, 96.8%, p < 0.001) than the latter group. CONCLUSIONS: CUSUM demonstrated that at least 29 successful cases are required to achieve an expertized manipulation in ultrasound-guided AxV cannulation for inexperienced novices. The learning curve for ultrasound-guided AxV cannulation was observed in 29 cases. After adequate training, the overall procedural time and the first-attempt success rate, and puncture-related complications for AxV cannulation improved with increased experience.


Subject(s)
Axillary Vein , Catheterization, Central Venous , Adult , Humans , Axillary Vein/diagnostic imaging , Catheterization, Central Venous/adverse effects , Catheterization, Central Venous/methods , Prospective Studies , Ultrasonography, Interventional/methods , Ultrasonography , Jugular Veins/diagnostic imaging
5.
Minerva Anestesiol ; 88(9): 660-667, 2022 09.
Article in English | MEDLINE | ID: mdl-35416464

ABSTRACT

BACKGROUND: Distinguishing light-echoed nerves from surrounding structures is challenging but may be important in nerve block administration. We evaluated the effect of patient characteristics on the echogenicity or visibility of the popliteal sciatic nerve (PSN). METHODS: This study included adult patients who presented to the operating room as volunteers. The primary outcome was the success rate of nerve identification by ultrasound using different PSN access paths. The secondary outcome included the PSN visibility score (VIS), scan time, and PSN depth. Logistic regression analysis was used to identify factors associated with the PSN identification success rate. The Body Mass Index (BMI) proximal-based cut-off was used to compare the PSN identification success rate through different access paths. RESULTS: The PSN was successfully identified in 89.7% of the volunteers. The access paths (P<0.01) and BMI (P=0.01) were identified as independent predictors of successful PSN identification. A higher PSN identification success rate (P=0.01), a higher VIS (P<0.01), a more superficial PSN depth (P<0.01), and a shorter scan time (P<0.01) were observed in the above-knee lateral approach. Among volunteers with BMI≥26.77 kg/m2, the PSN identification success rate through the above-knee lateral approach was significantly higher (P<0.01), and PSN depth was shallower (P<0.01) than through the medial approach. CONCLUSIONS: The ultrasound-guided above-knee lateral approach for PSN block improved the PSN identification success rate, ensured a more superficial nerve location, and provided a clearer image.


Subject(s)
Nerve Block , Sciatic Nerve , Adult , Humans , Knee , Nerve Block/methods , Sciatic Nerve/diagnostic imaging , Ultrasonography , Ultrasonography, Interventional/methods , Volunteers
6.
Ann Palliat Med ; 10(5): 5188-5197, 2021 May.
Article in English | MEDLINE | ID: mdl-33977744

ABSTRACT

BACKGROUND: Ultrasound guidance has become a standard method for detection of nerve structures in regional anesthesia. During ultrasound-guided blockade, to identify anatomical structures is crucial but can be challenging. In clinical practice, we find a wide difference in the visibility score of the sciatic nerve (SN) through different approaches. This study aimed to compare SNB through the anterior and above-knee lateral approach in terms of identification ease, performance efficacy, and safety. METHODS: Patients scheduled for below-knee surgery were randomized to either receive SNB using the above-knee lateral approach (Group L, n=27) or the anterior approach (Group A, n=26). The primary outcome was the visibility score of SN. Secondary outcomes included the time taken to identify the SN, nerve depth, success rate of SN identification, number of needle passes, time to elicit foot flexion, needle depth, and occurrence of SNB complications. Additionally, the sensory block onset and analgesia duration were assessed. RESULTS: We included 53 adult patients. Compared with Group A, Group L showed a higher SN visibility score [3.25 (3.17, 3.67) vs. 2.50 (1.86, 2.68), P<0.001]. The scan time was significantly shorter in Group L [8.70 (6.01) s vs. 31.54 (11.87) s, P<0.001]. The depth of the SN was 3.20 (0.56) cm in Group L and 5.53 (0.84) cm in Group A (P<0.001), and the needle insertion depth was 7.15 (0.90) cm in group L and 8.32 (1.13) cm in Group A (P<0.001). The number of needle passes was less in Group L, as well as the time to elicit foot flexion, and the time taken to perform the SN block (all P<0.001). The success rate of SN identification was non-significantly higher in Group L. There was no significant between-group difference in the onset of sensory block, as well as postoperative analgesia duration. None of the approaches involved acute systemic toxicity and hematoma occurrence. CONCLUSIONS: Based on the visibility score, the above-knee lateral approach allowed easy SN identification and safe SNB. Using the ultrasound-guided above-knee lateral approach for SNB in below-knee surgeries could be a reliable choice.


Subject(s)
Anesthesia, Conduction , Nerve Block , Adult , Humans , Sciatic Nerve/diagnostic imaging , Ultrasonography , Ultrasonography, Interventional
7.
Ann Palliat Med ; 10(3): 2439-2447, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33440972

ABSTRACT

BACKGROUND: In balanced anesthesia, protocol during the last 30 min is very important to guarantee rapid emergence and smooth extubation. In clinical practice, sevoflurane and propofol are often used in combination to achieve a better anesthetic effect and less adverse reaction. Approximately 30 min before surgical completion, sevoflurane inhalation is often discontinued and propofol is adjusted to keep sufficient depth of anesthesia. However, propofol-based anesthesia may delay time to emergence due to its unpredictable interindividual variability. In contrast, sevoflurane can be rapidly excreted unchanged from the respiratory tract, and more importantly, with minimal variability. This study aimed to investigate the effect of a novel balanced anesthesia protocol, that is propofol-based intravenous induction, propofol-sevoflurane combined maintenance, and total sevoflurane inhalation during the last 30 min of the surgery, on the time to emergence/extubation. METHODS: In our study, a total of 100 female patients undergoing modified radical mastectomy were enrolled. All patients received propofol-based intravenous anesthesia for induction followed by propofolsevoflurane combined maintenance. Approximately 30 min before the end of surgery, sevoflurane was continually inhaled without propofol infusion in group Sev (n=50), while propofol was only infused in group Pro (n=50). The primary outcome was the time to emergence/extubation. The second outcomes included time to respiratory recovery, and duration of post-anesthesia care unit (PACU) stay. The hemodynamic parameters and incidences of postoperative adverse events such as hypoxemia, nausea, vomiting, dizziness, and emergence agitation (EA) were also assessed. RESULTS: The time to emergence/extubation in group Sev was shorter than that in group Pro (12.74±4.31 vs. 17.74±4.27 min, P<0.0001). Similarly, time to respiratory recovery, and duration of PACU stay were significantly shortened in group Sev (all P<0.0001). Most of the patients in group Sev were extubated under a totally waking state of consciousness. The hemodynamic parameters and incidences of postoperative hypoxemia, nausea, vomiting, dizziness, and EA during the PACU stay were similar between the two groups. CONCLUSIONS: In patients undergoing modified radical mastectomy, this novel balanced anesthesia method could shorten the time to emergence/extubation and better waking state without increasing the incidence of adverse events.


Subject(s)
Anesthetics, Inhalation , Balanced Anesthesia , Breast Neoplasms , Methyl Ethers , Anesthesia Recovery Period , Anesthesia, Inhalation , Anesthetics, Inhalation/adverse effects , Anesthetics, Intravenous , Breast Neoplasms/surgery , Female , Humans , Mastectomy , Mastectomy, Modified Radical , Prospective Studies
8.
Ann Palliat Med ; 10(2): 1207-1215, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33040561

ABSTRACT

BACKGROUND: To guarantee efficient operating room (OR) activity, tracheal extubation is often performed in the postanesthesia care unit (PACU). Therefore, the ability of PACU to accommodate postoperative patients is crucial. Optimizing extubation management may speed up the turnover of PACU beds. The aim of the present study was to investigate the effect of remifentanil, which is used during analepsia, on the length of PACU stay in patients undergoing laparoscopic surgery for endometrial cancer. METHODS: In this prospective trial, we recruited a total of 99 patients, who were scheduled for laparoscopic surgery for endometrial cancer. At the end of the surgery, all patients were immediately transferred to the PACU and continued mechanical ventilation. Upon PACU admission, sputum aspiration was routinely performed. If the hemodynamic parameters fluctuated >30% of the baseline level, or patients moved unconsciously without reaching the criteria of extubation, a bolus injection of either 1 µg/kg remifentanil (Rem group, n=51) or propofol 1.0 mg/kg (Pro group, n=48) was randomly administered. The primary outcome was the duration of PACU stay. The secondary outcomes included time to respiratory breath recovery and time to extubation, along with bispectral index (BIS) values and hemodynamic status after remifentanil or propofol intervention. Times of repeated intervention, rescue administration of vasoactive drugs, and the incidence of adverse events were recorded. Visual analog scale and satisfaction scores at the time of PACU discharge were also evaluated. RESULTS: The duration of PACU stay was shorter in the Rem group than in the Pro group [49 (46.47-51.06 minutes) vs. 62 minutes (60.75-69.29 minutes), P<0.0001]. Compared with the Pro group, the time to spontaneous breathing recovery, the time to extubation, and the incidence of hypoxemia after extubation were reduced in the Rem group (P<0.0001, P<0.0001, P=0.03, respectively). After anesthetic administration, the BIS value decreased less in the Rem group (P<0.0001); blood pressure and heart rate (HR) declined, but were comparable in both groups. CONCLUSIONS: Remifentanil, which is injected during analepsia, significantly shortens the duration of PACU stay without increasing adverse events in the peri-extubation period.


Subject(s)
Endometrial Neoplasms , Laparoscopy , Anesthetics, Intravenous , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/surgery , Female , Humans , Piperidines/therapeutic use , Prospective Studies , Remifentanil/therapeutic use
9.
Drug Deliv Transl Res ; 11(5): 1969-1982, 2021 10.
Article in English | MEDLINE | ID: mdl-33006741

ABSTRACT

Balancing the antitumor activity and systemic toxicity of tripterine still faces a big challenge due to the narrow therapeutic window. To address this issue, we report a microemulsion system based on tripterine, brucea oil, and glycyrrhizin, and dual modified with both transferrin and cell-penetrating peptide SA-R6H4 (Tf/SA-R6H4-TBG-MEs) for combinational and tumor-targeted cancer therapy. Such a microemulsion exhibited a spherical shape with a size of ~50 nm and a mildly-negative charge. The half-maximal inhibitory concentration (IC50) of Tf/SA-R6H4-TBG-MEs against ovarian cancer SKOV3 cells was 0.27 ± 0.43 µg tripterine/mL, which was 5.85 times lower than that of free tripterine. The cellular uptake of tripterine after treatment with Tf/SA-R6H4-TBG-MEs was 1.56 times higher than that of TBG-MEs (non-modified microemulsion). In pharmacokinetics studies, the area under the curve of Tf/SA-R6H4-TBG-MEs increased by 1.97 times compared with that of the physical mixture group. The tumoral accumulation of tripterine was significantly improved in Tf/SA-R6H4-TBG-MEs group than TBG-MEs-treated group. In antitumor efficacy in vivo, Tf/SA-R6H4-TBG-MEs exhibited the strongest inhibition of tumor growth and the longest survival period among all the groups, which is associated with the rational combination, microemulsion system, and dual modification with tumor-targeted ligands. Importantly, Tf/SA-R6H4-TBG-MEs significantly reduced the toxicity of tripterine against the liver and kidney. Our design provides a new approach for efficient and safe ovarian cancer therapy based on a multicomponent combination.


Subject(s)
Cell-Penetrating Peptides , Coix , Ovarian Neoplasms , Cell Line, Tumor , Emulsions , Humans , Ovarian Neoplasms/drug therapy , Transferrin
10.
Drug Des Devel Ther ; 14: 5155-5166, 2020.
Article in English | MEDLINE | ID: mdl-33262576

ABSTRACT

BACKGROUND: Lung resection and one lung ventilation (OLV) during video-assisted thoracoscopic surgery (VATS) may lead to acute lung injury. Dexmedetomidine (DEX), a highly selective α2 adrenergic receptor agonist, improves arterial oxygenation in adult patients undergoing thoracic surgery. The aim of this pilot study was to explore possible mechanism related to lung protection of DEX in patients undergoing VATS. PATIENTS AND METHODS: Seventy-four patients scheduled for VATS were enrolled in this study. Three timepoints (before anesthesia induction (T0), 40 min after OLV (T1), and 10 min after two-lung ventilation (T2)) of arterial blood gas were obtained. Meanwhile, lung histopathologic examination, immunohistochemistry analysis (occludin and ZO-1), levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in lung tissue and plasma, and activation of phosphoinositide-3-kinase (PI3K)/AKT/hypoxia-inducible factor (HIF)-1α signaling were detected. Postoperative outcomes including duration of withdrawing the pleural drainage tube, length of hospital stay, hospitalization expenses, and postoperative pulmonary complications (PPCs) were also recorded. RESULTS: Sixty-seven patients were randomly divided into DEX group (group D, n=33) and control group (group N, n=34). DEX improved oxygenation at T1 and T2 (group D vs group N; T1: 191.8 ± 49.8 mmHg vs 159.6 ± 48.1 mmHg, P = 0.009; T2: 406.0 mmHg [392.2-423.7] vs 374.5 mmHg [340.2-378.2], P = 0.001). DEX alleviated the alveolar capillary epithelial structure damage, increased protein expression of ZO-1 and occludin, inhibited elevation of the expression of TNF-α and IL-6 in lung tissue and plasma, and increased protein expression of p-PI3K, p-AKT and HIF-1α. Dex administered had better postoperative outcomes with less risk of PPCs and hospitalization expenses as well as shorter duration of withdrawing the pleural drainage tube and length of hospital stay. CONCLUSION: Activation of PI3K/Akt/HIF-1α signaling might be involved in lung protection of DEX in patients undergoing VATS.


Subject(s)
Acute Lung Injury/drug therapy , Acute Lung Injury/surgery , Adrenergic alpha-2 Receptor Agonists/pharmacology , Dexmedetomidine/pharmacology , Thoracic Surgery, Video-Assisted , Acute Lung Injury/metabolism , Adrenergic alpha-2 Receptor Agonists/administration & dosage , Adrenergic alpha-2 Receptor Agonists/chemistry , Dexmedetomidine/administration & dosage , Dexmedetomidine/chemistry , Female , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Male , Middle Aged , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Pilot Projects , Prospective Studies , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects
11.
Onco Targets Ther ; 12: 7437-7450, 2019.
Article in English | MEDLINE | ID: mdl-31686849

ABSTRACT

BACKGROUND: The application of gene-loaded microbubbles (MBs) combined with ultrasound that results in increased delivery efficiency may be an excellent method of gene delivery. This study aimed to discuss the effects of ultrasound-MB-mediated microRNA (miR)-449a on lung cancer (LC) development by targeting Notch1. METHODS: Initially, miR-449a expression in LC tissues, paracancerous tissues, LC cell lines, and lung epithelial cells was detected and its association with LC patients' clinical characteristics was analyzed. The gain-of-function studies were performed to probe the roles of miR-449a and ultrasound-MB-mediated miR-449a in LC progression. Then, RT-qPCR combined with Western blot analysis was applied to verify the levels of miR-449a, Notch1, proliferation- and apoptosis-related proteins. Moreover, xenograft tumors in nude mice were also applied for in vivo experiments. RESULTS: Poorly expressed miR-449a was observed in LC, and its expression was associated with clinical staging, differentiation and lymph node metastasis of LC patients. Overexpression of miR-449a suppressed LC cell proliferation and promoted G2/M arrest and apoptosis. Ultrasound-MB-mediated miR-449a strengthened inhibitory effects of miR-449a on cell growth and resistance to apoptosis. miR-449a inhibited H1299 cell activity by targeting Notch1. CONCLUSION: Our data supported that miR-449a overexpression inhibited LC cell growth, and ultrasound-MB-mediated miR-449a reinforced the repressive effects of miR-449a on LC progression. This investigation may offer new insight for LC treatment.

12.
Medicine (Baltimore) ; 97(22): e10907, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29851818

ABSTRACT

RATIONALE: Tracheobronchomalacia (TBM) refers to the weakening trachea or the trachea loss of structural integrity of airway cartilaginous structures. It causes tracheal stenosis, resulting in significantly high rates of mortality. Bronchoplasty by high-pressure balloon dilation under general anesthesia is a simple but effective and safe method to treat tracheobronchial stenosis. However, recurrent postoperative dyspnea after extubation due to tracheal collapse is still a challenge for anesthetists. PATIENT CONCERNS: A 52-year-old man weighing 72 kg was scheduled for balloon dilatation surgery under general anesthesia because of breathing difficulties caused by tracheal stenosis. His previous medical history included rheumatoid arthritis, obstructive sleep apnea syndrome (OSAS), chronic bronchitis and a history of tracheal intubation. Laryngeal computerized tomography confirmed the stenosis at the level of thyroid gland. DIAGNOSIS: The tracheal collapse after balloon dilatation for tracheal stenosis therapy. INTERVENTIONS: Postoperatively, the patient presented with more serious and repetitive symptoms of dyspnea after extubation when compared to that before treatment. So, we had to re-insert the laryngeal mask airway (LMA), and exclude some anesthesia-associated factors, such as laryngospasm, bronchospasm and so on. After a series of treatments, we ultimately found the cause in time (the airway collapsed), and succeeded in tracheal extubation after the stent was inserted. OUTCOMES: The patient recovered well and reported high satisfaction with anesthesia management. LESSONS: In such an emergency even, the anesthesiologist should take valuable treatments to ensure the patient's effective ventilation. If the anesthesia-related factors can be eliminated, tracheomalacia or airway collapse should be considered whenever dyspnea occurs in the patients who unexpectedly fail to be extubated.


Subject(s)
Airway Extubation/adverse effects , Dilatation/adverse effects , Intubation, Intratracheal/adverse effects , Postoperative Complications/etiology , Tracheal Stenosis/therapy , Tracheomalacia/etiology , Airway Extubation/methods , Device Removal , Dilatation/methods , Humans , Male , Middle Aged , Postoperative Complications/pathology , Stents , Trachea/pathology , Trachea/surgery , Tracheal Stenosis/complications , Tracheomalacia/pathology
13.
Biochem Biophys Res Commun ; 501(2): 365-373, 2018 06 22.
Article in English | MEDLINE | ID: mdl-29705706

ABSTRACT

Activated pancreatic stellate cells (PSCs) play a crucial role in the progression of pancreatic fibrosis. Transforming growth factor-ß (TGF-ß) is one of the strongest stimulator inducing fibrosis. The mitogen-activated protein kinase (MAPK) proteins (including ERK, JNK and p38 MAPK) are known to contribute to PSC activation and pancreatic fibrosis. Previous studies have identified PSC activation induced by TGF-ß1 is related to MAPK pathway, but the respective role of MAPK family members in PSC activation still unclear, and which family member may be the key mediator in mice PSC activation still controversial. In this study, we investigated the influence of different MAPK family member (JNK, ERK, and p38 MAPK) on mice PSC activation using an in vivo and in vitro model. The results showed p-JNK, p-ERK and p-p38 MAPK were all over-expressed in CP group, and p-JNK, p-ERK, and p-p38 MAPK were co-expressed with activated PSC. In vitro, TGF-ß1 induced JNK and ERK over-expression in PSCs. In contrast, p38 MAPK expression in PSC showed only a very weak increase. JNK- and ERK-specific inhibitors inhibited FN and α-SMA mRNA expression in PSCs, and a p38 MAPK inhibitor had no effect on PSC activation. These findings indicate that JNK and ERK were directly involved in the PSCs activation induced by TGF-ß1 and the development of pancreatic fibrosis. p38 MAPK participate in the progression of CP, but it does not respond to TGF-ß1 directly and may not be regarded as the target of TGF-ß1 induced PSC activation.


Subject(s)
Mitogen-Activated Protein Kinases/metabolism , Pancreatic Stellate Cells/metabolism , Pancreatitis, Chronic/pathology , Transforming Growth Factor beta1/pharmacology , Animals , Extracellular Matrix/drug effects , Extracellular Matrix/metabolism , Gene Expression Regulation, Enzymologic/drug effects , MAP Kinase Signaling System/drug effects , Male , Mice , Mitogen-Activated Protein Kinases/antagonists & inhibitors , Mitogen-Activated Protein Kinases/genetics , Pancreatic Stellate Cells/drug effects , Pancreatitis, Chronic/metabolism , Protein Kinase Inhibitors/pharmacology , Receptors, Transforming Growth Factor beta/genetics , Receptors, Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta1/metabolism
14.
World J Gastroenterol ; 23(40): 7242-7252, 2017 Oct 28.
Article in English | MEDLINE | ID: mdl-29142471

ABSTRACT

AIM: To explore the role of macrophages in chronic pancreatitis (CP) and the effect of Dachaihu decoction (DCHD) on pancreatic fibrosis in mice. METHODS: KunMing mice were randomly divided into a control group, CP group, and DCHD group. In the CP and DCHD groups, mice were intraperitoneally injected with 20% L-arginine (3 g/kg twice 1 d/wk for 6 wk). Mice in the DCHD group were administered DCHD intragastrically at a dose of 14 g/kg/d 1 wk after CP induction. At 2 wk, 4 wk and 6 wk post-modeling, the morphology of the pancreas was observed using hematoxylin and eosin, and Masson staining. Interleukin-6 (IL-6) serum levels were assayed using an enzyme-linked immunosorbent assay. Double immunofluorescence staining was performed to observe the co-expression of F4/80 and IL-6 in the pancreas. Inflammatory factors including monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α) and IL-6 were determined using real time-polymerase chain reaction. Western blot analysis was used to detect fibronectin levels in the pancreas. RESULTS: Compared with the control group, mice with 20% L-arginine-induced CP had obvious macrophage infiltration and a higher level of fibrosis. IL-6 serum concentrations were significantly increased. Double immunofluorescence staining showed that IL-6 and F4/80 were co-expressed in the pancreas. With the administration of DCHD, the infiltration of macrophages and degree of fibrosis in the pancreas were significantly attenuated; IL-6, MCP-1 and MIP-1α mRNA, and fibronectin levels were reduced. CONCLUSION: The dominant role of macrophages in the development of CP was mainly related to IL-6 production. DCHD was effective in ameliorating pancreatic fibrosis by inhibiting macrophage infiltration and inflammatory factor secretion in the pancreas.


Subject(s)
Drugs, Chinese Herbal/therapeutic use , Macrophages/drug effects , Pancreas/pathology , Pancreatitis, Chronic/drug therapy , Animals , Arginine/toxicity , Chemokine CCL2/metabolism , Chemokine CCL3/metabolism , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Fibronectins/metabolism , Fibrosis , Humans , Interleukin-6/blood , Interleukin-6/metabolism , Macrophages/immunology , Macrophages/metabolism , Medicine, Chinese Traditional/methods , Mice , Pancreas/drug effects , Pancreatitis, Chronic/blood , Pancreatitis, Chronic/chemically induced , Pancreatitis, Chronic/immunology , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction
15.
World J Gastroenterol ; 22(10): 2960-70, 2016 Mar 14.
Article in English | MEDLINE | ID: mdl-26973392

ABSTRACT

AIM: To search for a new chronic pancreatitis model in mice suitable for investigating the pathophysiological processes leading to pancreatic fibrosis. METHODS: The mice were randomly divided into 2 groups (n = 50), control group and model group. The mice in model group were given ethanol (10%) in drinking water after injection of dibutyltin dichloride (DBTC) (8 mg/kg BW) in tail vein. The mice in control group were injected with only solvent into tail vein (60% ethanol, 20% glycerine and 20% normal saline) and drank common water. At days 1, 7, 14, 28, and 56 after application of DBTC or solvent, 10 mice in one group were killed at each time point respectively. Blood was obtained by inferior vena cava puncture. The activity of amylase, concentration of bilirubin and hyaluronic acid in serum were assayed. The pancreas was taken to observe the pancreatic morphology by HE staining, and to characterize the pancreatic fibrosis by Masson staining. The expression of F4/80, CD3 and fibronectin (FN) were assayed by immuno-histochemistry or Immunofluorescence technique. Collagen type I (COL1A1) in pancreas were detected by Western blot. The expression of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA in the pancreas was assessed by real time PCR. RESULTS: DBTC induced an acute edematous pancreatitis within 1 d. The dilated acini, scattered acinar cell necrosis, and inflammatory cells were found at day 7. Extensive infiltration with inflammatory cells following deposition of connective tissue was observed at day 14. At day 28, level of pancreatic fibrosis was aggravated. The pancreatic tissue was replaced by an extended interstitial fibrosis at the end of 2 mo. There was significant difference in the level of amylase, bilirubin and hyaluronic acid in serum between control group and model group (P < 0.05). The level of COL1A1 and FN in pancreas increased. The expression of MMP-1 mRNA in pancreas decreased, but TIMP-1 mRNA increased at model group. CONCLUSION: DBTC joint Ethanol drinking can induce chronic pancreatitis in accordance with the pathophysiological modification of human. DBTC joint Ethanol-induced pancreatitis in mice is an effective and handy experimental method. The model is suitable to study the mechanism of pancreatic fibrosis in chronic pancreatitis.


Subject(s)
Ethanol , Organotin Compounds , Pancreas/physiopathology , Pancreatitis, Chronic/chemically induced , Animals , Biomarkers/blood , Disease Models, Animal , Fibrosis , Gene Expression Regulation , Matrix Metalloproteinase 13/genetics , Matrix Metalloproteinase 13/metabolism , Mice , Pancreas/metabolism , Pancreas/pathology , Pancreatitis, Chronic/blood , Pancreatitis, Chronic/pathology , Pancreatitis, Chronic/physiopathology , Time Factors , Tissue Inhibitor of Metalloproteinase-1/metabolism
16.
J BUON ; 19(3): 692-7, 2014.
Article in English | MEDLINE | ID: mdl-25261654

ABSTRACT

PURPOSE: This study aimed to investigate the efficacy and safety of transcatheter arterial chemoembolization (TACE) in combination with three-dimensional conformal radiotherapy (3D-CRT) in the treatment for locally advanced unresectable hepatocellular carcinoma (HCC). METHODS: From March 2000 to March 2009 a total of 158 patients with unresectable HCC treated and followed at our hospital were divided into TACE group (N=80) and TACE combined with 3D-CRT group (N=78). The TACE group was treated 3-6 times. In the combination group, 2-3 TACE courses were administered and 3D-CRT was performed 2 weeks after the last TACE. Three months after the end of treatment, imaging and serum AFP were carried out to assess the treatment efficacy. RESULTS: The response rates of TACE and the combination groups were 53.7% (43/80) and 71.8% (58/78) (p<0.05). The 1, 2, and 3-year survival rates of patients in the TACE and combination groups were 58.75, 36.25, 16.25%, and 78.48, 55.12 and 25.64% (p<0.05), respectively. Treatment compliance was good, with at least 2 TACE administrations for each case and at least 52 Gy for radiotherapy. In the TACE and the combination group, there were 2 and 3 cases with grade III/IV toxicity, respectively, without treatment-related death. CONCLUSION: 3D-CRT in combination with TACE significantly improve the therapeutic outcome in patients with locally advanced unresectable HCC, without creating severe toxicity.


Subject(s)
Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic/methods , Liver Neoplasms/therapy , Radiotherapy, Conformal/methods , Adolescent , Adult , Aged , Carcinoma, Hepatocellular/mortality , Chemoembolization, Therapeutic/adverse effects , Combined Modality Therapy , Female , Humans , Liver Neoplasms/mortality , Male , Middle Aged , Radiotherapy, Conformal/adverse effects
17.
Asian Pac J Cancer Prev ; 14(6): 3949-53, 2013.
Article in English | MEDLINE | ID: mdl-23886213

ABSTRACT

AIM: To investigate the effectiveness and adverse effects of gemcitabine by fixed-dose rate infusion plus oxaliplatin (GEMOX regimen) as second-line therapy for advanced ovarian cancer. METHODS: 64 patients with advanced ovarian cancer were divided into an experimental group (44 cases) and a control group (20 cases). The experimental group was treated with continuous intravenous infusion of gemcitabine at 1000 mg/m(2) with a fixed-dose rate of 10 mg/m(2)/min, on days 1 and 8 and oxaliplatin at 100 mg/m(2) on day 1, IVGTT, repeated every 3 weeks. The control group was treated with intravenous infusion of gemcitabine at 1000 mg/m(2) within 30 min on days 1 and and oxaliplatin at 100 mg/m(2) on day 1, IVGTT, again repeated every 3 weeks. CT scans or MRI were used for review every 1-2 cycles. RESULTS: The effective rate in the experimental group was significantly high than control group (43.2% vs 35.0%; P < 0.05), with no obvious difference of hematologic or non-hematologic toxicity between the two groups (P > 0.05). CONCLUSION: GEMOX regimen is very effective to treat advanced ovarian cancer, with low toxicity, good tolerance and improved life quality in patients.


Subject(s)
Adenocarcinoma, Clear Cell/mortality , Adenocarcinoma, Mucinous/mortality , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cystadenocarcinoma, Serous/mortality , Deoxycytidine/analogs & derivatives , Endometrial Neoplasms/mortality , Ovarian Neoplasms/mortality , Adenocarcinoma, Clear Cell/drug therapy , Adenocarcinoma, Clear Cell/pathology , Adenocarcinoma, Mucinous/drug therapy , Adenocarcinoma, Mucinous/pathology , Adult , Aged , Case-Control Studies , Cystadenocarcinoma, Serous/drug therapy , Cystadenocarcinoma, Serous/pathology , Deoxycytidine/therapeutic use , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/pathology , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Staging , Organoplatinum Compounds/therapeutic use , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Prognosis , Quality of Life , Survival Rate
18.
Asian Pac J Cancer Prev ; 13(6): 2967-71, 2012.
Article in English | MEDLINE | ID: mdl-22938491

ABSTRACT

OBJECTIVE: To explore whether monoclonal antibodies against stathmin and the chemotherapuetic agent paclitaxel have synergenic effects in inhibiting growth and inducing apoptosis in human QG-56 cells. METHODS: QG-56 cells were treated with monoclonal antibodies against stathmin or paclitaxel alone or in combination, with untreated cells used as controls. After 24, 48, 72 and 96 hours the cell growth condition was observed under an inverted microscope and inhibition was studied by MTT assay; apoptosis was analyzed by flow cytometry. RESULTS: The populations decreased and cell shape and size changed after the various treatments. Monoclonal antibodies against stathmin and paclitaxel used alone or incombination inhibited the proliferation of QG-56 cells, especially in combination with synergism (P<0.05). Combined treatment also resulted in a significantly higher apoptosis rate than in the other groups (P<0.05). CONCLUSIONS: Monoclonal antibodies against stathmin and paclitaxel used alone or in combination can inhibit proliferation of QG-56 cells and induce apoptosis when applied together, The observed synergistic effects may have important implications for clinical application.


Subject(s)
Adenocarcinoma/drug therapy , Antibodies, Monoclonal/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Lung Neoplasms/drug therapy , Paclitaxel/pharmacology , Stathmin/immunology , Adenocarcinoma/pathology , Adenocarcinoma of Lung , Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents, Phytogenic/therapeutic use , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Combined Modality Therapy , Drug Synergism , Humans , Lung Neoplasms/pathology , Paclitaxel/therapeutic use
19.
Asian Pac J Cancer Prev ; 13(1): 361-5, 2012.
Article in English | MEDLINE | ID: mdl-22502701

ABSTRACT

AIMS: To investigate the relationship between the expression of ß-tubulin III and survivin in advanced breast cancers and chemotherapeutic effects of docetaxel. METHODS: Clinical pathological data of 74 patients with advanced breast cancer were retrospectively analyzed after docetaxel chemotherapy. Expression of ß-tubulin III and survivin was assessed by immunohistochemistry and analyzed with reference to therapeutical and adverse effects of docetaxel. RESULTS: The positive expression rate of ß-tubulin III was 38.1% (32/84), while that of survivin was 76.2% (64/84). The effective rate (complete response + partial response) was 52.4%. That for patients with the positive expression of ß-tubulin III or/and survivin was significantly lower than for those with negative expression (P<0.05). There were significant differences in the non-progression of median diseases, 1-year and 2-year survival rates of between the patients with positive and negative expression (P<0.05). The main side effects were myelosuppression, alimentary canal response and alopecia, no differences being observed between groups. CONCLUSIONS: The combined detection of ß-tubulin III and survivin is a predictive index for chemotherapy effects of docetaxel in metastatic breast cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/metabolism , Breast Neoplasms/metabolism , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Lobular/metabolism , Drug Resistance, Neoplasm , Inhibitor of Apoptosis Proteins/metabolism , Tubulin/metabolism , Adult , Aged , Breast Neoplasms/drug therapy , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Ductal, Breast/mortality , Carcinoma, Ductal, Breast/secondary , Carcinoma, Lobular/drug therapy , Carcinoma, Lobular/mortality , Carcinoma, Lobular/secondary , Cyclophosphamide/administration & dosage , Docetaxel , Doxorubicin/administration & dosage , Female , Humans , Middle Aged , Prognosis , Remission Induction , Retrospective Studies , Survival Rate , Survivin , Taxoids/administration & dosage
SELECTION OF CITATIONS
SEARCH DETAIL
...