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1.
Artigo em Inglês | MEDLINE | ID: mdl-36572783

RESUMO

PURPOSE: SHC014748M is a potent, novel selective PI3Kδ isoform inhibitor and is proposed for the treatment of non-Hodgkin lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma. This study investigated the pharmacokinetics, mass balance, metabolism and excretion of SHC014748M in Chinese male subjects following a single oral dose of 150 mg (100 µCi) [14C] SHC014748M. METHODS: Six healthy Chinese male subjects administrated an oral suspension of 150 mg (100 µCi) [14C] SHC014748M and the samples of blood, urine and feces were collected for measuring. Liquid chromatography-tandem mass spectrometry and liquid scintillation counter were utilized to obtain mass balance and the pharmacokinetic data. RESULTS: The median Tmax for [14C]-radioactivity was 1.6 ± 0.5 h after the oral administration of [14C] SHC014748M and the mean Cmax was 3863 ± 354 ng Eq./mL in plasma, while the mean Cmax, t1/2 values and AUC0-∞ values for total radioactivity in whole blood were 2466 ± 518 ng Eq./mL, 32.2 ± 30.5 h and 66,236 ± 44,232 h * ng Eq./mL, respectively. Fecal excretion was proposed as the predominant elimination route, accounting for a mean of 90.68 ± 11.38% of the administered dose, whereas the mean urine excretion was 6.00 ± 1.48% within 336 h post-dose. The proposed major metabolic pathway of [14C] SHC014748M in the human body were as follows: (I) monooxidation, (II) glucuronide acid conjugation, and (III) monoxide-hydrogenation. CONCLUSIONS: SHC014748M was absorbed, metabolized and excreted with unchanged SHC014748M as its main circulating component in plasma following oral administration. In addition, it was speculated that fecal excretion was the principal excretion pathway; meanwhile, monohydroxy, glucuronide conjugation, oxygen, and hydrogenation were the major clearance pathways of SHC014748M through urine and/or feces. TRIAL REGISTRATION: The trial registration number: CTR20202505.

2.
Int Wound J ; 2022 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-36575064

RESUMO

Pressure injury often seriously affects the life quality of aged patients, especially the long-term bedridden casualties. Widely adopted by different disciplines, negative pressure suction has its role in pressure injury. Microskin implantation has been demonstrated powerful in increasing the expansion ratio of donor area-derived skin and accelerating wound healing by forming "skin islands". The study was designed to evaluate the efficacy and safety of additional use of bedside microskin implantation in the palliative care of pressure injury of aged patients who cannot tolerate surgical treatment as a supplement for standard negative pressure suction. An open-label within-patient RCT was conducted in aged patients with pressure injury. Sixteen patients were enrolled. After granulation tissues formed, half of a pressure injury was randomised to receive the negative pressure suction as the control group, and the other half exposed to additional bedside microskin implantation as the experimental group. Efficacy was evaluated within 1 month after treatment, and the primary endpoints included the wound healing rate and pressure ulcer scale for healing (PUSH) scores. The secondary outcomes included survival rate of implanted microskin, pain intensity assessment, satisfaction surveys from patients or their family, and pressure ulcer healing complications. Sixteen patients completed the study. After 14 days of operation, 5.63 ± 1.78 out of 10 pieces of implanted microskin survived and formed neonatal epithelium. The wound healing rates of the control group and the experimental group at 1 month were (26.17 ± 9.03%) and (35.95 ± 16.02%), respectively (P < .01). The mean PUSH score before the surgery was 12.38 ± 2.23. At 1 month after surgery, the mean difference of PUSH score from baseline was 2.13 ± 0.96 in the control group and 2.81 ± 0.83 in the experimental group (P < .01). The treatment of microskin implantation did not cause additional pain or complications to the patients. Accompanied by a better ulcer status, the majority of patients or their guardians have a high degree of acceptance towards the microskin implantation. Bedside microskin implantation could accelerate wound healing with lower PUSH scores. As a complementary palliative treatment, supplementary microskin implantation is effective and well tolerated.

3.
Front Pharmacol ; 13: 957660, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36210838

RESUMO

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of systemic autoimmune diseases, which is typified by inflammatory necrosis predominantly affecting the small vessels and often accompanied by positive ANCA. Clinically, AAV primarily includes microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA). It has been found that in AAV pathogenesis, both innate and adaptive immunity are related to neutrophil function mutually. Many proteins, such as myeloperoxidase (MPO) and proteinase 3 (PR3), in neutrophil cytoplasm lead to the production of proteins such as MPO-ANCA and PR3-ANCA by activating adaptive immunity. In addition, through the process of neutrophil extracellular trap (NET) formation, activation of an alternative complement pathway and the respiratory burst can stimulate the neutrophils close to vascular endothelial cells and will participate the vessel inflammation. This review aims to reveal the potential mechanisms regulating the association between the neutrophils and various types of AAVs and to emphasize the results of recent findings on these interactions. Moreover, multiple underlying signaling pathways involved in the regulation of neutrophils during AAV processes have also been discussed. The ultimate goal of this review is to identify novel biomarkers and therapeutic targets for AAV management in the future.

4.
Front Genet ; 13: 878554, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35846114

RESUMO

The WUSCHEL-related homeobox (WOX) proteins are widely distributed in plants and play important regulatory roles in growth and development processes such as embryonic development and organ development. Here, series of bioinformatics methods were utilized to unravel the structural basis and genetic hierarchy of WOX genes, followed by regulation of the WOX genes in four Euphorbiaceae species. A genome-wide survey identified 59 WOX genes in Hevea brasiliensis (H. brasiliensis: 20 genes), Jatropha curcas (J. curcas: 10 genes), Manihot esculenta (M. esculenta: 18 genes), and Ricinus communis (R. communis: 11 genes). The phylogenetic analysis revealed that these WOX members could be clustered into three close proximal clades, such as namely ancient, intermediate and modern/WUS clades. In addition, gene structures and conserved motif analyses further validated that the WOX genes were conserved within each phylogenetic clade. These results suggested the relationships among WOX members in the four Euphorbiaceae species. We found that WOX genes in H. brasiliensis and M. esculenta exhibit close genetic relationship with J. curcas and R. communis. Additionally, the presence of various cis-acting regulatory elements in the promoter of J. curcas WOX genes (JcWOXs) reflected distinct functions. These speculations were further validated with the differential expression profiles of various JcWOXs in seeds, reflecting the importance of two JcWOX genes (JcWOX6 and JcWOX13) during plant growth and development. Our quantitative real-time PCR (qRT-PCR) analysis demonstrated that the JcWOX11 gene plays an indispensable role in regulating plant callus. Taken together, the present study reports the comprehensive characteristics and relationships of WOX genes in four Euphorbiaceae species, providing new insights into their characterization.

5.
Dis Markers ; 2022: 8942985, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35774850

RESUMO

Objectives: The study is aimed at exploring the effect of the controlled release of the glial-derived neurotrophic factor (GDNF) on nerve regeneration. Methods: The PLGA/chitosan composite nerve conduit was used to bridge the dissected trunk of the rat facial nerve. GDNF microcapsules were loaded into the nerve conduit. Nine weeks after surgery, the facial nerve zygomatic and buccal branches were labeled with fluorescent indicators. The incorrectly grown facial neurons were reversed and counted. The facial nerve functional recovery was assessed by measuring the maximum evoked potential. Results: The nerve conduit was filled with different regenerating factors, such as the GDNF, GDNF microcapsules, or saline (control). The number of incorrectly regenerated neurons was lower with the nerve conduits filled with GDNF microcapsules than with those supplied with just the GDNF. However, neither the GDNF nor GDNF microcapsules affected the number of regenerated neurons. The functional recovery of the facial nerve was the best, with the nerve conduit filled with GDNF microcapsules closest to the healthy uncut facial nerve. Conclusion: The stable slow-release GNDF microcapsule inside the biodegradable nerve conduit can reduce the extent of incorrect growth of the facial nerve neuron when bridging the dissected rat facial nerve trunk. The technique has a good effect on functional nerve recovery.


Assuntos
Nervo Facial , Fator Neurotrófico Derivado de Linhagem de Célula Glial , Animais , Cápsulas/farmacologia , Preparações de Ação Retardada/farmacologia , Nervo Facial/cirurgia , Fator Neurotrófico Derivado de Linhagem de Célula Glial/farmacologia , Regeneração Nervosa , Ratos
6.
Clin Pharmacol Drug Dev ; 11(11): 1273-1283, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35844038

RESUMO

Telitacicept, an injectable recombinant human B-lymphocyte stimulating factor receptor-antibody fusion protein, is a new dual B lymphocyte stimulator (BLyS)/APRIL (a proliferation-inducing ligand) inhibitor that effectively blocks proliferation of B lymphocytes. This study evaluates the pharmacokinetic characteristics, tolerability, and safety of a single subcutaneous injection of various doses (80, 160, and 240 mg) of telitacicept in healthy Chinese subjects. This trial is a single-center, randomized, open-label phase I clinical study that includes three dose groups (80, 160, and 240 mg) with 12 subjects in each dose group. The subjects were randomly assigned to different dose groups in a 1:1:1 ratio for a single subcutaneous administration trial. After a single dose, the maximum serum concentration (Cmax ) of total and free telitacicept was reached within 0.5-1 days. The elimination half-lives of total and free telitacicept at doses of 80-240 mg were 10.9-11.9 days and 11-12.5 days, respectively. The formation and elimination of the BLyS-telitacicept complex were much slower; the median time to Cmax was 15-57 days and was significantly prolonged with increasing dose. Only two of the 36 healthy subjects had positive antidrug antibodies with antibody titers of 1:15. The severity of adverse events was mild or moderate, and no higher treatment-emergent adverse events were reported. In conclusion, total telitacicept within a dose range of 80-240 mg and free telitacicept within a dose range of 160-240 mg had linear pharmacokinetic characteristics.


Assuntos
Linfócitos B , Imunossupressores , Humanos , Proteínas Recombinantes de Fusão/efeitos adversos , Voluntários Saudáveis , Relação Dose-Resposta a Droga , China
7.
ACS Omega ; 7(23): 19412-19419, 2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35721997

RESUMO

Miscanthus floridulus fibers obtained from the seed floss of M. floridulus (a perinneal plant of Gramineae native to Africa and Asia and widely distributed in tropical and subtropical regions) have potential application value in textile and other fields. At present, the biological characteristics and ecological benefits of Miscanthus floridus have been extensively studied by researchers, but there have been no literature on M. floridus fibers. In order to make reasonable use of M. floridus fibers, their morphological structure, physical properties, chemical composition, thermal insulation properties, and surface absorption properties were explored in detail in this study. The results showed that the M. floridus fiber is fine and short and has a hollow structure with a density of 0.67 g cm-3. Chemical analyses revealed that the main constituents of the fiber are cellulose (66.98%), hemicelluloses (13.86%), lignin (6.97%), pectin (1.99%), and wax (4.38%). The fill power and warmth retention performance of the fiber are similar to those of wool. In particular, the M. floridus fiber surface has hydrophobic and lipophilic properties with a static contact angle of 123.7° for water droplets in equilibrium. Therefore, the M. floridus fiber has a promising application prospect in bulk textile thermal insulation and oil-water separation fields.

9.
Cell Death Dis ; 13(4): 327, 2022 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-35397613

RESUMO

Bortezomib, a proteasome inhibitor, proved potent in the treatment of recurrent multiple myeloma or mantle cell lymphoma. However, slow progress was made when it was applied to treat solid tumors. We discovered that different head and neck squamous cell carcinoma (HNSCC) cell lines had significantly different sensitivities to bortezomib, and also demonstrated that individual relatively sensitive HNSCC cell lines had fewer ΔNp63α expressions. Based on these findings, we speculated that ΔNp63α may be a key factor in the resistance of HNSCC cells to bortezomib. ΔNp63α knockdown made HNSCC more sensitive to bortezomib, while ΔNp63α overexpression made it more resistant. RNA sequencing (RNA-seq) analysis of ΔNp63α-knockdown cells revealed clear alterations in the subset of genes that were associated with oxidative stress and antioxidant defense. The gene CYGB was downregulated significantly. CHIP-seq detection showed that CYGB was the transcriptional regulatory site of ΔNp63α. CHIP-PCR showed evidence of ΔNp63α binding. The detection of the dual-luciferase reporter gene demonstrated that ΔNp63α significantly enhanced the CYGB promoter activity. Furthermore, we confirmed that CYGB plays a role in clearing excess ROS induced by bortezomib to inhibit HNSCC apoptosis. Consequently, ΔNp63α regulated the expression of CYGB in HNSCC. CYGB was the target of transcription regulation of ΔNp63α. It reduced apoptosis by clearing excess ROS produced by bortezomib, and thus exerted drug resistance.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Adulto , Bortezomib/farmacologia , Bortezomib/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/genética , Humanos , Recidiva Local de Neoplasia/genética , Espécies Reativas de Oxigênio/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética
10.
Artigo em Inglês | MEDLINE | ID: mdl-35301171

RESUMO

BACKGROUND: The long-term sleep state has an important influence on one's physical and mental health. Melatonin (MEL) and cortisol with circadian rhythm are deemed to be potential sleep biomarkers. Considering the rapid metabolism of MEL and cortisol, their main metabolites could be alternative indicators showing higher stability and reliability. However, there is short of research developing the method for simultaneous quantification of MEL, cortisol and their metabolites in hair. OBJECTIVES: This study aimed to develop a method for the simultaneous quantification of F, MEL and their main metabolites (cortisone; N-acetyl-serotonin, NAS; 6-hydroxymelatonin, 6-O-MEL and 6-sulfatoxymelatonin, S-O-MEL) in human hair based on high-performance liquid chromatography tandem mass spectrometry method, and then explore the relationship between the biomarkers' contents and sleep state. METHODS: Analytes were extracted from 20-mg hair in 1 mL methanol at about 27°C, and then analyzed in a mobile phase of 95% methanol and 5% 5 mM ammonium acetate, and identified with an electrospray ionization source in positive ion mode. Hair samples closest to the scalp were collected from 65 undergraduates. Sleep state was measured based on participants' scores of the Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale and the Morningness/Eveningness Questionnaire. RESULTS: The method showed good linearity with the square of correlation coefficient > 0.99 at the ranges of 0.1-1000 pg/mg for MEL, 0.4-1000 pg/mg for NAS, 1.0-1000 pg/mg for 6-O-MEL, 1.0-1000 pg/mg for S-O-MEL, 0.5-1000 pg/mg for cortisol and 1.0-1000 pg/mg for cortisone. It showed the limit of detection ranged from 0.05 to 0.3 pg/mg and the limit of quantification ranged between 0.1 and 1.0 pg/mg for the six analytes. The inter- and intra-day coefficients of variation were < 20%. The compounds could be detected in natural hair samples except for S-O-MEL. The average concentration was 0.18 pg/mg for MEL, 3.5 pg/mg for NAS, 3.8 pg/mg for 6-O-MEL, 20.0 pg/mg for cortisone and 2.8 pg/mg for cortisol. The population analysis revealed that there was positive association between hair cortisone and sleep quality. CONCLUSIONS: This study had developed an LC-MS/MS method for simultaneous quantification of MEL, NAS, 6-O-MEL, cortisone and cortisol in human hair. Hair cortisone might be a promising biomarker of long-term sleep state.


Assuntos
Glucocorticoides , Melatonina , Cromatografia Líquida/métodos , Glucocorticoides/análise , Cabelo/química , Humanos , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos
11.
J Otolaryngol Head Neck Surg ; 51(1): 8, 2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35216636

RESUMO

BACKGROUND: This study investigated the role of lncRNA CASC15 in laryngeal squamous cell carcinoma (LSCC). METHODS: This study included 58 LSCC patients. Both tumor (LSCC) and adjacent (within 3 cm around tumors) non-tumor tissues from 3 different sites of each patient were collected. CCK-8 assay was used to determine cell proliferation. The expression levels of proteins and mRNAs were determined by Western blotting analysis and qRT-PCRs, respectively. RESULTS: CASC15 was upregulated in LSCC and high expression levels of CASC15 predicted poor survival. In LSCC tissues, CASC15 was negatively correlated with miR-365 but positively correlated with cyclin D1. In LSCC cells, overexpression of CASC15 resulted in downregulation of miR-365 and upregulation of cyclin D1. Overexpression of miR-365 did not affect the expression of CASC15 but downregulated cyclin D1. Overexpression of Cyclin D1 did not affect the expression of miR-365 and CASC15. Overexpression of CASC15 and cyclin D1 led to promoted, while overexpression of miR-365 led to inhibited LSCC cell proliferation. In addition, overexpression of miR-365 reduced the effects of overexpression of CASC15. CONCLUSION: Therefore, CASC15 upregulates cyclin D1 by downregulating miR-365 in LSCC to promote cell proliferation.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Laríngeas , MicroRNAs , RNA Longo não Codificante , Carcinoma de Células Escamosas/patologia , Proliferação de Células/genética , Ciclina D1/genética , Ciclina D1/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Humanos , Neoplasias Laríngeas/patologia , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Regulação para Cima
12.
Wounds ; 34(12): 283-287, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36622378

RESUMO

INTRODUCTION: New techniques are needed to manage chronic wounds in patients with contraindications to standard of care treatment. OBJECTIVE: This case series investigated the viability and proliferative activity of split skin cells harvested from the discarded rolled edge of PIs for use in promoting reepithelialization in chronic wounds. MATERIALS AND METHODS: The harvested skin was minced into particles with a scalpel. The structure of the skin particle was shown with hematoxylin-eosin staining. The viability of cells, isolated from skin particles, was identified with MTT. Skin particles were transferred to PIs. The size of PI was recorded before grafting and 1 month after grafting. RESULTS: From January 2018 to January 2019, 5 patients (1 female, 4 males; mean age, 72.6 years ± 6.1) were enrolled in this study. The mean ulcer size was 27.8 cm2 ± 17.7. The cells from particles could survive and be amplified in vitro. One month after grafting, the average ulcer size was 16.2 cm2 ± 7.3. CONCLUSION: The split skin particles harvested from the rolled edge of the wound consisted of keratinocytes and keratinized tissues and were found to be viable and proliferative. These particles had the capacity to survive and expand on the granulation tissue surface of PIs, which indicates this procedure could accelerate reepithelization in chronic wounds.


Assuntos
Lesão por Pressão , Transplante de Pele , Idoso , Feminino , Humanos , Masculino , Estudos de Viabilidade , Pele/lesões , Transplante de Pele/métodos , Cicatrização
13.
Crit Rev Eukaryot Gene Expr ; 31(6): 17-22, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34936289

RESUMO

The oncogenic functions of circRNA circSEPT9 have been characterized in triple-negative breast cancer. We analyzed its role in laryngeal squamous cell carcinoma (LSCC). Quantitative reverse-transcription PCR (RT-qPCR) was used to analyze the expression of circSEPT9 and miR-10a in paired LSCC and nontumor tissues donated by 50 patients with LSCC. Methylation-specific PCR (MSP) was performed to analyze the role of circSEPT9 in miR-10a RNA gene methylation. circSEPT9 or miR-10a were overexpressed in LSCC cells to explore the interaction between them. The regulatory role of circSEPT9 and miR-10a in cell proliferation was studied with cell counting kit-8 (CCK-8) assay. CircSEPT9 was highly expressed in LSCC, whereas miR-10a was expressed at a lower level in LSCC. CircSEPT9 and miR-10a were closely correlated across LSCC tissue samples. In LSCC cells, circSEPT9 overexpression increased the methylation of the miR-10a gene and decreased the expression of miR-10a. CircSEPT9 overexpression increased LSCC cell proliferation, whereas miR-10a overexpression decreased cell proliferation. Co-transfection experiments showed that circSEPT9 overexpression attenuated the effects of miR-10a overexpression on cell proliferation. We conclude that circSEPT9 may increase miR-10a methylation to increase cell proliferation in LSCC.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Laríngeas , MicroRNAs , Carcinoma de Células Escamosas de Cabeça e Pescoço , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Humanos , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patologia , Metilação , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética
14.
Expert Opin Drug Metab Toxicol ; 17(9): 1149-1156, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34372746

RESUMO

PURPOSE: To compare the pharmacokinetics, pharmacodynamics and safety of the new prolonged-release leuprorelin acetate microspheres for injection (3.75 mg) with the reference product Enantone® (3.75 mg). METHOD: 48 healthy male volunteers were enrolled and randomly received a single 3.75 mg dose of the test drug or Enantone®. RESULTS: There were no significant differences in Cmax, AUC0-t and AUC0-48 between the test group and reference group (P > 0.05). The 90% confidence intervals of the two groups were 87.49%~112.74%, 97.15%~154.25%, and 80.85%~109.01%, respectively. Twenty-eight days after administration, both groups reached 100.0% castration level; there was no difference in the time from administration to reaching castration level between the two groups (P > 0.05); However, the difference between the two groups in the duration of castration level was statistically significant (P < 0.05). There were no major or serious adverse events, and the severity was mild to moderate. CONCLUSION: The pharmacokinetic characteristics of leuprorelin in two groups were consistent. The two groups exhibited similar inhibitory effects on testosterone and more subjects in the test group maintained a longer castration time than those in the reference group.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Leuprolida/administração & dosagem , Testosterona/sangue , Adulto , Antineoplásicos Hormonais/farmacocinética , Antineoplásicos Hormonais/farmacologia , Área Sob a Curva , Preparações de Ação Retardada , Humanos , Injeções , Leuprolida/farmacocinética , Leuprolida/farmacologia , Masculino , Microesferas , Método Simples-Cego , Fatores de Tempo , Adulto Jovem
15.
Respir Physiol Neurobiol ; 293: 103720, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34146730

RESUMO

The pathogenesis of obstructive sleep apnea (OSA) remains controversial. The role of anatomic stenosis is indisputable, and neural regulation of the upper airway remains to be elucidated. The upper airway maintains patency through the upper airway reflex. Lesions in any link of the reflex can increase the collapsibility of the upper airway. In this study, we investigated sensorimotor nerve lesions and their possible relationship with OSA. Tissue samples were obtained from the pharyngopalatine arch in 47 patients with OSA and 45 control participants to examine changes in the expression levels of myelin basic protein (MBP) and agrin through immunohistochemistry and western blotting. Downregulation of MBP in the mucosa reflects myelinated degeneration of mucosal sensory nerve axons, whereas upregulation of agrin in the neuromuscular junction reflects synaptic regeneration following denervation. The two neural factors correlate significantly with polysomnographic parameters, such as the apnea hypopnea index and lowest oxygen saturation. Our findings suggest that sensorimotor nerve damage in the upper airway of patients with OSA may be associated closely with the mechanism of OSA.


Assuntos
Agrina/metabolismo , Axônios/patologia , Proteína Básica da Mielina/metabolismo , Junção Neuromuscular/patologia , Mucosa Respiratória/inervação , Células Receptoras Sensoriais/patologia , Apneia Obstrutiva do Sono , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Polissonografia , Apneia Obstrutiva do Sono/metabolismo , Apneia Obstrutiva do Sono/patologia , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/cirurgia , Adulto Jovem
16.
J Asian Nat Prod Res ; 23(12): 1135-1139, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33463380

RESUMO

Two new benzo[de]isoquinoline derivatives, 4-phenyl-benzo[de]isoquinoline-1,3-dione (1) and 4-(4-hydroxyphenyl)-benzo[de]isoquinoline-1,3-dione (2), were isolated from 70% ethanol extract of the rhizomes of Musa basjoo. Their chemical structures were elucidated by HRESIMS, 1 D and 2 D spectra.


Assuntos
Musa , Rizoma , Estrutura Molecular
17.
Front Pharmacol ; 12: 798735, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35058782

RESUMO

Objective: To clarify the molecular mechanism of TMEM88 regulating lipid synthesis and metabolism cytokine in NAFLD. Methods: In vivo, NAFLD model mice were fed by a Methionine and Choline-Deficient (MCD) diet. H&E staining and immunohistochemistry experiments were used to analyze the mice liver tissue. RT-qPCR and Western blotting were used to detect the lipid synthesis and metabolism cytokine. In vitro, pEGFP-C1-TMEM88 and TMEM88 siRNA were transfected respectively in free fat acid (FFA) induced AML-12 cells, and the expression level of SREBP-1c, PPAR-α, FASN, and ACOX-1 were evaluated by RT-qPCR and Western blotting. Results: The study found that the secretion of PPAR-α and its downstream target ACOX-1 were upregulated, and the secretion of SREBP-1c and its downstream target FASN were downregulated after transfecting with pEGFP-C1-TMEM88. But when TMEM88 was inhibited, the experimental results were opposite to the aforementioned conclusions. The data suggested that it may be related to the occurrence, development, and end of NAFLD. Additionally, the study proved that TMEM88 can inhibit Wnt/ß-catenin signaling pathway. Meanwhile, TMEM88 can accelerate the apoptotic rate of FFA-induced AML-12 cells. Conclusion: Overall, the study proved that TMEM88 takes part in regulating the secretion of lipid synthesis and metabolism cytokine through the Wnt/ß-catenin signaling pathway in AML-12 cells. Therefore, TMEM88 may be involved in the progress of NAFLD. Further research will bring new ideas for the study of NAFLD.

18.
Adv Sci (Weinh) ; 8(22): e2102666, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34523247

RESUMO

Necrosis induces strong inflammation with undesirable implications in clinics compared with apoptosis. Fortunately, the switch between necrosis and apoptosis could be realized by tailoring the appropriate structural properties of gold nano rods (GNRs) that could precisely modulate cell death pathways. Herein, the intracellular interaction between GNRs and organelles is monitored and it is found that lysosomes dominates necrosis/apoptosis evoking. Then the surface molecule density of GNRs, which is first defined as ρsurf. molecule (Nsurf. molecules /(a × π × Diameter × Length)), mediates lysosome activities as the membrane permeabilization (LMP), the Cathepsin B and D release, the cross-talk between lysosome and different organelles, which selectively evokes apoptosis or necrosis and the production of TNF-α from macrophages. GNRs with small ρsurf. molecule mainly induce apoptosis, while with large ρsurf. molecule they greatly contribute to necrosis. Interestingly, necrosis can be suppressed by GNRs with higher ρsurf. molecule due to the overexpression of key protease caspase 8, which cleaves the RIP1-RIP3 complex and activates caspase 3 followed by necrosis to apoptosis transition. This investigation indicates that the ρsurf. molecule greatly affects the utility of nanomaterials and different structural properties of nanomaterials have different implications in clinics.


Assuntos
Apoptose , Ouro/química , Nanotubos/química , Neoplasias/metabolismo , Neoplasias/patologia , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Nus , Necrose
19.
Artigo em Chinês | MEDLINE | ID: mdl-33254295

RESUMO

Objective:To analyze the therapeutic effect of internal carotid artery resection and one-stage revascularization in advanced cervical metastatic carcinoma. Method:Twenty-one patients with advanced head and neck malignant tumors who underwent internal carotid artery resection and one-stage revascularization were analyzed retrospectively. Among those, 11 patients suffered from hypo-pharyngeal carcinomas, 5 laryngeal carcinomas, 2 external auditory carcinomas, 1 middle ear carcinoma, and 2 parotid gland carcinomas. All patients received CT, MRI, DSA and other examinations before operation. It was found that all the internal carotid artery walls had been invaded by tumors, and there were different degrees of lumen stenosis. Autogenous saphenous vein grafts were used in 18 cases; artificial vessels were used in 3 cases. After revascularization, pedicled or free flaps were used to protect the anastomotic areas. All patients were treated with radiotherapy and chemotherapy according to different situations. Result:Among the 21 cases, 16 cases underwent reconstruction of cervical segment internal carotid and 5 cases were the skull base segment internal carotid. Twenty patients were successfully reconstructed in the first stage, and no vascular reconstruction-related nervous system complications occurred after operations. Postoperative imaging showed that the reconstructed blood vessels were well recanalized, with a success rate of 95.2%(20/21). Only 1 case received ligation of internal carotid artery after the failure of vascular reconstruction. Among all the cases, the 1-year survival rate and 3-year survival rate were 90.5% and 40.4%, respectively. Conclusion:In patients with advanced head and neck malignant tumors with cervical metastatic cancer invading the internal carotid artery, one-stage revascularization after radical resection of the tumor and the internal carotid can achieve good therapeutic effect. Careful preoperative evaluation, proficient vascular anastomosis technology, adequate risk assessment and prevention are the key to the success of the operations.


Assuntos
Artéria Carótida Interna , Neoplasias de Cabeça e Pescoço , Artéria Carótida Interna/cirurgia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Estudos Retrospectivos , Base do Crânio , Procedimentos Cirúrgicos Vasculares
20.
Adv Healthc Mater ; 9(20): e2001032, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32902190

RESUMO

Systemic antibiotic therapy is the main treatment for acute bacterial rhinosinusitis (ABRS). However, this treatment often causes side effects of dizziness, diarrhea, and drug resistance. In this study, a new polyethylene glycol hydrogel (PEG-H) treatment model is developed to achieve sustained release of drugs at the locality while avoiding those adverse effects. The PEG-H is composed of 4-arm-PEG-SH and silver ions through a high affinity and dynamic reversible coordination bond between the thiol and silver ion. In the initial test, PEG-H is loaded with Clarithromycin (CAM-Lips@Hydrogel) or Clarithromycin and Budesonide liposomes (CAM+BUD-Lips@Hydrogel). The results show that PEG-H maintains the characteristics of self-healing, biodegradability, moderate swelling rate, injectibility and sustained drug release. In in vivo studies, the hydrogel is injected into the maxillary sinus of ABRS rabbit models. In both a single or combined load, the hydrogel not only plays an effective role as an anti-bacterial, but also inhibits inflammatory response of local sinus mucosa. In addition, no other side effects are observed in the ABRS rabbit model through behavioral observation and drug sensitivity tests. Therefore, the injectable self-healing hydrogel with anti-bacterial and anti-inflammatory properties provides a new micro invasive therapeutic method for the clinical treatment of ABRS.


Assuntos
Hidrogéis , Polietilenoglicóis , Animais , Anti-Inflamatórios/farmacologia , Materiais Biocompatíveis , Liberação Controlada de Fármacos , Coelhos
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