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1.
Ear Nose Throat J ; : 1455613241256520, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38808678

ABSTRACT

Malignant melanoma originating from the sphenoid sinus is an extremely rare but aggressive tumor of the head and neck. A 57-year-old man had a 1 month history of headache, right trigeminal paresthesias, and upper lid ptosis. Magnetic resonance imaging showed a large mass in the right sphenoid sinus and an invasion of the right cavernous sinus and clivus. The patient underwent endoscopic endonasal transsphenoidal surgery, and pathologically revealed malignant melanoma. One month after the operation, the patient was treated with radiation therapy. Unfortunately, the patient died of distant metastasis 2 years later. Due to its rarity, there is still no effective treatment strategy and no way to assess the progression of malignant melanoma.

2.
PLoS One ; 18(6): e0287147, 2023.
Article in English | MEDLINE | ID: mdl-37310979

ABSTRACT

OBJECTIVE: To identify the most effective fraction of Nanocnide lobata in the treatment of burn and scald injuries and determine its bioactive constituents. METHODS: Chemical identification methods were used to analyze solutions extracted from Nanocnide lobata using petroleum ether, ethyl acetate, n-butanol using a variety of color reactions. The chemical constituents of the extracts were identified by ultra-performance liquid chromatography (UPLC)-mass spectrometry (MS). A total of 60 female mice were randomly divided into the following 6 groups: the petroleum ether extract-treated group; the ethyl acetate extract-treated group; the n-butanol extract-treated group; the model group; the control group; and the positive drug group. The burn/scald model was established using Stevenson's method. At 24 hours after modeling, 0.1 g of the corresponding ointment was evenly applied to the wound in each group. Mice in the model group did not undergo treatment, while those in the control group received 0.1 g of Vaseline. Wound characteristics, including color, secretions, hardness, and swelling, were observed and recorded. Photos were taken and the wound area calculated on the 1st, 5th, 8th, 12th, 15th, 18th and 21st days. Hematoxylin-eosin (HE) staining was utilized to observe the wound tissue of mice on the 7th, 14th, and 21st days. An enzyme-linked immunosorbent assay (ELISA) kit was used to measure the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-10, vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-ß1. RESULTS: The chemical constituents of Nanocnide lobata mainly include volatile oils, coumarins, and lactones. UPLC-MS analysis revealed 39 main compounds in the Nanocnide lobata extract. Among them, ferulic acid, kaempferitrin, caffeic acid, and salicylic acid have been confirmed to exhibit anti-inflammatory and antioxidant activity related to the treatment of burns and scalds. HE staining revealed a gradual decrease in the number of inflammatory cells and healing of the wounds with increasing time after Nanocnide lobata extract administration. Compared with the model group, the petroleum ether extract-treated group showed significant differences in the levels of TNF-α (161.67±4.93, 106.33±3.21, 77.67±4.04 pg/mL) and IL-10 (291.77±4.93, 185.09±9.54, 141.33±1.53 pg/mL) on the 7th, 14th, and 21st days; a significant difference in the content of TGF-ß1 (75.68±3.06 pg/mL) on the 21st day; and a significant difference in the level of VEGF (266.67±4.73, 311.33±10.50 pg/mL) on the 7th and 14th days respectively. CONCLUSION: Petroleum ether Nanocnide lobata extract and the volatile oil compounds of Nanocnide lobata might be effective drugs in the treatment of burn and scald injuries, as they exhibited a protective effect on burns and scalds by reducing the expression of TNF-α, IL-10 and TGF-ß1 and increasing the expression of VEGF. In addition, these compounds may also exert pharmacological effects that promote wound tissue repair, accelerate wound healing, and reduce scar tissue proliferation, inflammation and pain.


Subject(s)
Burns , Interleukin-10 , Female , Animals , Mice , Transforming Growth Factor beta1 , Vascular Endothelial Growth Factor A , 1-Butanol , Chromatography, Liquid , Tumor Necrosis Factor-alpha , Tandem Mass Spectrometry , Burns/drug therapy
3.
Exp Ther Med ; 25(5): 215, 2023 May.
Article in English | MEDLINE | ID: mdl-37123210

ABSTRACT

The endoscope-assisted supraorbital keyhole approach and extended transsphenoidal approach have been widely used in the treatment of tuberculum sellae meningiomas (TSMs). The purpose of the present study was to retrospectively analyze and compare the characteristics and efficacy of the two surgical approaches under the endoscope in the resection of TSMs. In the present study, 36 patients with TSMs who underwent surgical resection are presented, including one group of 17 cases with an endoscopic supraorbital keyhole approach and the other group of 19 cases with an endoscopic extended transsphenoidal approach. The clinical characteristics, diagnosis, treatment process and treatment effect of the two groups were analyzed retrospectively, and the two surgical approaches were also compared. The gross total resection rates of the two groups were similar, reaching 94.5 and 94.7%, respectively. The postoperative visual acuity recovery showed that in the endoscopic supraorbital keyhole approach group, 23 eyes were improved, 8 eyes were maintained and 3 eyes deteriorated, and the visual recovery was 67.6%. In the endoscopic extended transsphenoidal approach group, 32 eyes were improved, 4 eyes were maintained and 2 eyes deteriorated, and the visual recovery was 84.2%. In the supraorbital keyhole approach group, there was no cerebrospinal fluid leakage, while in the extended transsphenoidal approach group, cerebrospinal fluid leakage occurred in 3 cases (15.8%). In these two groups, no tumor recurrence was revealed during the follow-up of ~5 years. Both the endoscope-assisted supraorbital keyhole approach and the extended transsphenoidal approach were effective and safe. The endoscopic supraorbital keyhole approach treated TSMs with lateral extension, but it was not enough to protect the optic nerve. The endoscopic extended transsphenoidal approach protected the optic nerve, but the risk of cerebrospinal fluid leakage was increased. In conclusion, these two surgical methods have their own advantages and limitations.

5.
Front Neurol ; 14: 1109388, 2023.
Article in English | MEDLINE | ID: mdl-37051052

ABSTRACT

Background: Pituitary neuroendocrinology tumors (PitNETs) with pseudocapsule can be effectively removed by the pseudocapsule-based extracapsular resection technique. In the areas without pseudocapsule, the tumor cells can spread into the adjacent tissues at the cellular level, which brings a great challenge to achieving total tumor resection. Methods: Our surgical strategy for PitNETs with an incomplete pseudocapsule is to combine the pseudocapsule-based extracapsular resection technique with the intensive excision technique for the removal of the tumor. Specifically, the pseudocapsule-based extracapsular resection technique is applied in the areas with pseudocapsule, while in the areas without pseudocapsule, the intensive excision technique bounded by adjacent normal structures is adopted. Moreover, a pathological examination was performed to determine the situations of pseudocapsule and tumor cell remnant. Results: All growth hormone-secreting PitNETs achieved biochemical remission after surgery. There was no deterioration of pituitary functions postoperatively, and the preoperative hypopituitarism had improved in all patients postoperatively. In total, two cases suffered a transient diabetes insipidus, and intraoperative cerebrospinal fluid leakage was observed in two cases but no postoperative cerebrospinal fluid leakage in all cases. There was no recurrence during the follow-up. The fragmental pseudocapsule and small tumor remnants were found in the majority of suspicious tissues by histological staining. Conclusion: The effectiveness and safety of the surgical strategy were preliminarily explored for removing PitNETs without incomplete pseudocapsules. In overview, the pseudocapsule-based extracapsular resection technique is applied in areas with pseudocapsule, while the intensive excision bounded by adjacent normal structures is adopted in other areas.

6.
World J Clin Cases ; 11(7): 1498-1505, 2023 Mar 06.
Article in English | MEDLINE | ID: mdl-36926405

ABSTRACT

BACKGROUND: Liver metastasis is the most common form of distant metastasis in colorectal cancer, and the only possible curative treatment for patients with colorectal liver metastases (CRLM) is hepatectomy. However, approximately 25% of patients with CRLM have indications for liver resection at the initial diagnosis. Strategies aimed at downstaging large or multifocal tumors to enable curative resection are appealing. CASE SUMMARY: A 42-year-old man was diagnosed with ascending colon cancer and liver metastases. Due to the huge lesion size and compression of the right portal vein, the liver metastases were initially diagnosed as unresectable lesions. The patient was treated with preoperative transcatheter arterial chemoembolization (TACE) consisting of 5-fluorouracil/Leucovorin/oxaliplatin/Endostar®. After four courses, radical right-sided colectomy and ileum transverse colon anastomosis were performed. Postoperatively, the pathological analysis revealed moderately differentiated adenocarcinoma with necrosis and negative margins. Thereafter, S7/S8 partial hepatectomy was performed after two courses of neoadjuvant chemotherapy. Pathological examination of the resected specimen revealed a pathologically complete response (pCR). Intrahepatic recurrence was detected more than two months after the operation, and the patient was then treated with TACE consisting of irinotecan/Leucovorin/fluorouracil therapy plus Endostar®. Subsequently, the patient was treated with a γ-knife to enhance local control. Notably, a pCR was reached, and the patient's overall survival time was > 9 years. CONCLUSION: Multidisciplinary treatment can promote the conversion of initially unresectable colorectal liver metastasis and facilitate complete pathological remission of liver lesions.

7.
Exp Ther Med ; 25(3): 137, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36845956

ABSTRACT

Minimally invasive spinal surgery (MISS) for intradural extramedullary (IDEM) spinal tumors is a safe and effective surgical strategy. Currently, various tubular retractors are widely used in the MISS of IDEM spinal tumors, primarily relying on microscopic visualization. To the best of the authors' knowledge, there is no report of pure endoscopic surgery with parallel non-expandable tubular retractors for IDEM spinal lesions. The present study reports a case series of IDEM spinal tumors that were treated via pure endoscopic MISS with a parallel non-expandable tubular retractor. The extent of tumor resection was evaluated by comparing preoperative and postoperative magnetic resonance imaging (MRI). The initial and follow-up clinical conditions were assessed according to the visual analog scale for pain and the modified McCormick scale for neurological status. Postoperative MRI demonstrated that all cases had achieved a gross total resection. After the operation, the clinical symptoms of all patients were significantly improved and there were no serious postoperative complications. At the initial follow-up, the pain experienced by the patients was significantly reduced or had even disappeared, and the neurological deficit was improved by at least one grade on the modified McCormick scale. The present report indicates that pure endoscopic MISS with a parallel non-expandable tubular retractor may be an effective and safe surgical strategy for IDEM spinal tumor resection.

8.
Rep Pract Oncol Radiother ; 28(6): 809-822, 2023.
Article in English | MEDLINE | ID: mdl-38515813

ABSTRACT

Background: This article aimed to compile and summarize clinically relevant literature in radiation therapy, and to discuss the potential in radioresistant and radiosensitive head and neck cancer. Study Design: Narrative review. Materials and methods: Google Scholar, PubMed and the Cochrane Library were retrieved using combined key words such as "radiotherapy" and "head and neck cancer". Search strings additionally queried were "radioresistant", "radiosensitive", "head and neck region", "squamous cell carcinoma", in combination with Boolean Operators 'AND' and 'OR'. Subsequently, the resulting publications were included for review of the full text. Results: Radiotherapeutic response currently in clinical observation referred to HNSCC scoping were selected into this review. The compiled mechanisms were then detailed concerning on the clinical significance, biological characteristics, and molecular function. Conclusions: Brachytherapy or/and external-beam radiotherapy are crucial for treating HNSCC, especially the early stage patients, but in patients with locally advanced tumors, their outcome with radiation therapy is poor due to obvious radioresistance. The curative effects mainly depend on the response of radiation therapy, so an updated review is needed to optimize further applications in HNSCC radiotherapy.

9.
J Pharm Anal ; 12(4): 645-652, 2022 Aug.
Article in English | MEDLINE | ID: mdl-36105165

ABSTRACT

Antibody-drug conjugates (ADCs) are commonly heterogeneous and require extensive assessment of exposure-efficacy and exposure-safety relationships in preclinical and clinical studies. In this study, we report the generation of a monoclonal antibody against monomethyl auristatin E (MMAE) and the development, validation, and application of sensitive and high-throughput enzyme-linked immunosorbent assays (ELISA) to measure the concentrations of MMAE-conjugated ADCs and total antibodies (tAb, antibodies in ADC plus unconjugated antibodies) in cynomolgus monkey sera. These assays were successfully applied to in vitro plasma stability and pharmacokinetic (PK) studies of SMADC001, an MMAE-conjugated ADC against trophoblast cell surface antigen 2 (TROP-2). The plasma stability of SMADC001 was better than that of similar ADCs coupled with PEG4-Val-Cit, Lys (m-dPEG24)-Cit, and Val-Cit linkers. The developed ELISA methods for the calibration standards of ADC and tAb revealed a correlation between serum concentrations and the OD450 values, with R 2 at 1.000, and the dynamic range was 0.3-35.0 ng/mL and 0.2-22.0 ng/mL, respectively; the intra- and inter-assay accuracy bias% ranged from -12.2% to -5.2%, precision ranged from -12.4% to -1.4%, and the relative standard deviation (RSD) was less than 6.6% and 8.7%, respectively. The total error was less than 20.4%. The development and validation steps of these two assays met the acceptance criteria for all addressed validation parameters, which suggested that these can be applied to quantify MMAE-conjugated ADCs, as well as in PK studies. Furthermore, these assays can be easily adopted for development of other similar immunoassays.

11.
Front Neurol ; 13: 1090478, 2022.
Article in English | MEDLINE | ID: mdl-36712457

ABSTRACT

Microvascular decompression is safe, effective, and micro-invasive. Due to these advantages, it has become the mainstream treatment for trigeminal neuralgia, glossopharyngeal neuralgia, and hemifacial spasm. Initially, microvascular decompression was performed under a microscope, which limited the light source and visualization capabilities. With the development of endoscopic technology, the endoscope has been used in microvascular decompression, which further improved the visualization range and light source properties. The purpose of the present study was to investigate the efficacy of fully endoscopic microvascular decompression for the treatment of trigeminal neuralgia. In total, three patients with trigeminal neuralgia who underwent fully endoscopic microvascular decompression were evaluated. After surgery, the facial pain of all patients was significantly relieved. In addition, there were no obvious postoperative complications and no recurrence after 6 months of follow-up. These excellent surgical outcomes indicate that fully endoscopic microvascular decompression is an effective and safe method for the treatment of trigeminal neuralgia. Furthermore, it also shows that the endoscope presents advantages for use in microvascular decompression.

12.
Front Surg ; 9: 1089632, 2022.
Article in English | MEDLINE | ID: mdl-36684351

ABSTRACT

With the advances in endoscopic technology, endoscopy is widely used in many neurosurgical procedures, such as microvascular decompression, which is an effective method to treat glossopharyngeal neuralgia, trigeminal neuralgia, and facial spasm. The purpose of this study was to determine the efficacy of fully endoscopic microvascular decompression in the treatment of glossopharyngeal neuralgia. We managed a patient with glossopharyngeal neuralgia in our department, whose main clinical manifestation was recurrent left ear and facial pain for 3 years. The patient underwent a fully endoscopic microvascular decompression. The pain in the left ear and face was significantly relieved postoperatively, and there was no recurrence at the 6-month follow-up evaluation. We describe a case of glossopharyngeal neuralgia that was successfully treated by fully endoscopic microvascular decompression, which showed that endoscopy has advantages in microvascular decompression, and fully endoscopic microvascular decompression is an effective method for glossopharyngeal neuralgia.

13.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-955477

ABSTRACT

Antibody-drug conjugates(ADCs)are commonly heterogeneous and require extensive assessment of exposure-efficacy and exposure-safety relationships in preclinical and clinical studies.In this study,we report the generation of a monoclonal antibody against monomethyl auristatin E(MMAE)and the development,validation,and application of sensitive and high-throughput enzyme-linked immunosor-bent assays(ELISA)to measure the concentrations of MMAE-conjugated ADCs and total antibodies(tAb,antibodies in ADC plus unconjugated antibodies)in cynomolgus monkey sera.These assays were suc-cessfully applied to in vitro plasma stability and pharmacokinetic(PK)studies of SMADC001,an MMAE-conjugated ADC against trophoblast cell surface antigen 2(TROP-2).The plasma stability of SMADC001 was better than that of similar ADCs coupled with PEG4-Val-Cit,Lys(m-dPEG24)-Cit,and Val-Cit linkers.The developed ELISA methods for the calibration standards of ADC and tAb revealed a correlation be-tween serum concentrations and the OD450 values,with R2 at 1.000,and the dynamic range was 0.3-35.0 ng/mL and 0.2-22.0 ng/mL,respectively;the intra-and inter-assay accuracy bias%ranged from-12.2%to-5.2%,precision ranged from-12.4%to-1.4%,and the relative standard deviation(RSD)was less than 6.6%and 8.7%,respectively.The total error was less than 20.4%.The development and validation steps of these two assays met the acceptance criteria for all addressed validation parameters,which suggested that these can be applied to quantify MMAE-conjugated ADCs,as well as in PK studies.Furthermore,these assays can be easily adopted for development of other similar immunoassays.

14.
Appl Opt ; 60(24): 7504-7510, 2021 Aug 20.
Article in English | MEDLINE | ID: mdl-34613041

ABSTRACT

In this paper, an optical fiber time transmission technology based on a double-fiber round-trip method is provided. In the system, the one-way transmission delay from the master station to the slave station can be calculated directly through the measurement of three time interval counters and their ratio relationship. The method eliminates the influence of fiber length expansion and round-trip transmission delay fluctuation, which is caused by ambient temperature change. The master and slave stations are connected by 100 km and 80 km optical fibers, respectively, and the temperature of the optical fiber link varies from -20∘C to 40°C. Compared with the single-fiber round-trip method, the time interval error of a double-fiber round-trip method is reduced from 1.4 ns to 80 ps when the wavelength is 1310-1550 nm, and from 320 to 80 ps when the wavelength is 1490-1550 nm.

15.
J Microbiol Biotechnol ; 30(12): 1876-1884, 2020 Dec 28.
Article in English | MEDLINE | ID: mdl-33046676

ABSTRACT

Ethanol often accumulates during the process of wine fermentation, and mitophagy has critical role in ethanol output. However, the relationship between mitophagy and ethanol stress is still unclear. In this study, the expression of ATG11 and ATG32 genes exposed to ethanol stress was accessed by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The result indicated that ethanol stress induced expression of the ATG11 and ATG32 genes. The colony sizes and the alcohol yield of atg11 and atg32 were also smaller and lower than those of wild type strain under ethanol whereas the mortality of mutants is higher. Furthermore, compared with wild type, the membrane integrity and the mitochondrial membrane potential of atg11 and atg32 exhibited greater damage following ethanol stress. In addition, a greater proportion of mutant cells were arrested at the G1/G0 cell cycle. There was more aggregation of peroxide hydrogen (H2O2) and superoxide anion (O2•-) in mutants. These changes in H2O2 and O2•- in yeasts were altered by reductants or inhibitors of scavenging enzyme by means of regulating the expression of ATG11 and ATG32 genes. Inhibitors of the mitochondrial electron transport chain (mtETC) also increased production of H2O2 and O2•- by enhancing expression of the ATG11 and ATG32 genes. Further results showed that activator or inhibitor of autophagy also activated or inhibited mitophagy by altering production of H2O2 and O2•. Therefore, ethanol stress induces mitophagy which improves yeast the tolerance to ethanol and the level of mitophagy during ethanol stress is regulated by ROS derived from mtETC.


Subject(s)
Ethanol/adverse effects , Mitochondria/metabolism , Mitophagy/physiology , Reactive Oxygen Species/metabolism , Saccharomyces cerevisiae/drug effects , Saccharomyces cerevisiae/metabolism , Autophagy/physiology , Autophagy-Related Proteins/metabolism , Cell Cycle , Cell Membrane/metabolism , Ethanol/metabolism , Fermentation , Hydrogen Peroxide/metabolism , Mitochondrial Membranes , Receptors, Cytoplasmic and Nuclear/metabolism , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae Proteins/metabolism , Superoxides/metabolism , Vesicular Transport Proteins/metabolism , Wine
16.
Am J Hypertens ; 33(1): 31-42, 2020 01 01.
Article in English | MEDLINE | ID: mdl-31328772

ABSTRACT

BACKGROUND: Essential hypertension is associated with increased plasma concentrations of extracellular vesicles (EVs). We aimed to determine the role of monocyte miR-27a in EVs on arterial Mas receptor expression, and its involvement in the pathogenesis of hypertension. METHODS: THP-1 cells were transfected with miR-27a mimic and miR-27a inhibitor, and EVs were collected. Mas receptor expression and endothelial nitric oxide synthase (eNOS) phosphorylation were determined by immunoblotting. Sprague-Dawley (SD) rats received EVs via tail-vein injection. Blood pressure (BP) was measured with the tail-cuff method. The vasodilatory response of mesenteric arteries was measured using a small vessel myograph. RESULTS: EVs from THP-1 cells increased rat BP by impairing Ang-(1-7)-mediated vasodilation in mesenteric arteries, which was further exaggerated by EVs from lipopolysaccharides-treated THP-1 cells. As the receptor and key signaling of Ang-(1-7), next experiments found that Mas receptor expression and eNOS phosphorylation were decreased in mesenteric arteries from EVs-treated SD rats. Screening studies found miR-27a in EVs may be involved in this process. Through transfection with miR-27a inhibitor or miR-27a mimic, we found that miR-27a downregulates Mas receptor expression in endothelial cells. Injection of EVs from miR-27a-transfected HEK-293 cells decreased Mas receptor and eNOS phosphorylation in mesenteric arteries, impaired Ang-(1-7)-mediated vasodilation and increased BP. Earlier effects were reversed using cells with downregulation of miR-27 in EVs. CONCLUSIONS: Monocyte miR-27a in EVs decreases Mas receptor expression and eNOS phosphorylation in endothelium, impairs Ang-(1-7)-mediated vasodilation, and causes hypertension. Understanding the contributions of EVs in the pathogenesis of hypertension may facilitate their use as a diagnostic biomarker.


Subject(s)
Blood Pressure , Extracellular Vesicles/metabolism , Hypertension/enzymology , Mesenteric Arteries/enzymology , MicroRNAs/metabolism , Monocytes/metabolism , Nitric Oxide Synthase Type III/metabolism , Proto-Oncogene Proteins/metabolism , Receptors, G-Protein-Coupled/metabolism , Animals , Disease Models, Animal , Extracellular Vesicles/genetics , Extracellular Vesicles/transplantation , HEK293 Cells , Humans , Hypertension/genetics , Hypertension/physiopathology , Male , Mesenteric Arteries/physiopathology , MicroRNAs/genetics , Monocytes/transplantation , Phosphorylation , Proto-Oncogene Mas , Rats, Sprague-Dawley , Signal Transduction , THP-1 Cells , Vasodilation
17.
Clin Case Rep ; 7(10): 1923-1927, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31624610

ABSTRACT

Patients with tongue squamous cell carcinoma (TSCC) and cervical lymph node metastasis are particularly difficult to treat. This is the first report of about anlotinib combined with docetaxel chemotherapy for chemotherapy-refractory TSCC with cervical lymph node metastasis, may provide a new, suitable therapeutic option for these patients.

18.
J Am Heart Assoc ; 8(8): e012192, 2019 04 16.
Article in English | MEDLINE | ID: mdl-30957627

ABSTRACT

Background Dopamine D5 receptor (D5R) plays an important role in the maintenance of blood pressure by regulating renal sodium transport. Our previous study found that human D5R mutant F173L transgenic ( hD 5 R F173L-TG) mice are hypertensive. In the present study, we aimed to investigate the mechanisms causing this renal D5R dysfunction in hD 5 R F173L-TG mice. Methods and Results Compared with wild-type D5R-TG ( hD 5 R WT-TG) mice, hD 5 R F173L-TG mice have higher blood pressure, lower basal urine flow and sodium excretion, and impaired agonist-mediated natriuresis and diuresis. Enhanced reactive oxygen species production in hD 5 R F173L-TG mice is caused, in part, by decreased expression of antioxidant enzymes, including thioredoxin 1 (Trx1). Na+-K+-ATPase activity is increased in mouse renal proximal tubule cells transfected with hD 5 R F173L, but is normalized by treatment with exogenous recombinant human Trx1 protein. Regulation of Trx1 by D5R occurs by the phospholipase C/ protein kinase C (PKC) pathway because upregulation of Trx1 expression by D5R does not occur in renal proximal tubule cells from D1R knockout mice in the presence of a phospholipase C or PKC inhibitor. Fenoldopam, a D1R and D5R agonist, stimulates PKC activity in primary renal proximal tubule cells of hD5R WT -TG mice, but not in those of hD 5 R F173L-TG mice. Hyperphosphorylation of hD5RF173L and its dissociation from Gαs and Gαq are associated with impairment of D5R-mediated inhibition of Na+-K+-ATPase activity in hD 5 R F173L-TG mice. Conclusions These suggest that hD 5 R F173L increases blood pressure, in part, by decreasing renal Trx1 expression and increasing reactive oxygen species production. Hyperphosphorylation of hD5RF173L, with its dissociation from Gαs and Gαq, is the key factor in impaired D5R function of hD 5 R F173L-TG mice.


Subject(s)
Blood Pressure/genetics , Hypertension/genetics , Natriuresis/genetics , Reactive Oxygen Species/metabolism , Receptors, Dopamine D5/genetics , Thioredoxins/genetics , Animals , Blood Pressure/drug effects , Chromogranins/metabolism , Diuresis/drug effects , Diuresis/genetics , Dopamine Agonists/pharmacology , Fenoldopam/pharmacology , GTP-Binding Protein alpha Subunits, Gq-G11/metabolism , GTP-Binding Protein alpha Subunits, Gs/metabolism , Gene Expression Regulation , Humans , Hypertension/metabolism , Kidney Tubules, Proximal/drug effects , Kidney Tubules, Proximal/metabolism , Mice , Mice, Knockout , Mice, Transgenic , Natriuresis/drug effects , Protein Kinase C/metabolism , Receptors, Dopamine D1/genetics , Receptors, Dopamine D5/metabolism , Signal Transduction , Thioredoxins/metabolism , Thioredoxins/pharmacology , Type C Phospholipases/metabolism
19.
RSC Adv ; 9(63): 37067-37078, 2019 Nov 11.
Article in English | MEDLINE | ID: mdl-35539080

ABSTRACT

For mitochondria-targeted nano-drug delivery systems against cancer, effectively targeting and releasing the drug into mitochondria are the keys to improve the therapeutic effect. In this study, mitochondria-targeted and reduction-sensitive micelles were developed to co-deliver doxorubicin (DOX) and evodiamine (EVO) for the treatment of metastatic breast cancer. After entering cancer cells, the micelles first targeted mitochondria through triphenylphosphonium cations. Then, the disulfide bonds of the micelles were cleaved by GSH, and both DOX and EVO were released near the mitochondria. The released EVO subsequently destroyed the mitochondrial membrane, resulting in a large amount of DOX entering the mitochondria and improving the anti-tumor effect of DOX. These mitochondria-targeted and reduction-sensitive micelles loaded with doxorubicin and evodiamine showed significant inhibition of the tumor cell growth both in vitro and in vivo.

20.
J Microbiol Biotechnol ; 28(12): 1982-1991, 2018 Dec 28.
Article in English | MEDLINE | ID: mdl-30394045

ABSTRACT

Ethanol accumulation inhibited the growth of Saccharomyces cerevisiae during wine fermentation. Autophagy and the release of reactive oxygen species (ROSs) were also induced under ethanol stress. However, the relation between autophagy and ethanol stress was still unclear. In this study, expression of the autophagy genes ATG1 and ATG8 and production of ROS under ethanol treatment in yeast were measured. The results showed that ethanol stress very significantly induced expression of ATG1 and ATG8 genes and the production of peroxide hydrogen (H2O2) and superoxide anion (O2·-). Moreover, the atg1 and atg8 mutants aggregated more H2O2 and O2·- than the wild-type yeast. In addition, inhibitors of the ROS scavenging enzyme induced expression of the ATG1 and ATG8 genes by increasing the levels of H2O2 and O2·-. In contrast, glutathione (GSH) and N-acetylcystine (NAC) decreased the ATG1 and ATG8 expression by reducing H2O2 and O2·- production. Rapamycin and 3-methyladenine also caused an obvious change in autophagy levels and simultaneously altered the release of H2O2 and O2·-. Finally, inhibitors of mitochondrial electron transport chain (mtETC) increased the production of H2O2 and O2·- and also promoted expression levels of the ATG1 and ATG8 genes. In conclusion, ethanol stress induced autophagy which was regulated by H2O2 and O2·- derived from mtETC, and in turn, the autophagy contributed to the elimination H2O2 and O2·-.


Subject(s)
Autophagy/drug effects , Ethanol/pharmacology , Gene Expression Regulation, Fungal/drug effects , Mitochondria/metabolism , Reactive Oxygen Species/metabolism , Saccharomyces cerevisiae/drug effects , Saccharomyces cerevisiae/metabolism , Autophagy/genetics , Autophagy-Related Protein 8 Family/genetics , Autophagy-Related Proteins/genetics , Cystine/analogs & derivatives , Cystine/metabolism , Fermentation , Glutathione/metabolism , Hydrogen Peroxide/metabolism , Mitochondrial Membranes , Mutation , Oxygen/metabolism , Protein Kinases/genetics , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae Proteins/genetics , Stress, Psychological , Superoxides/metabolism , Transcriptome , Wine
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