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1.
Microorganisms ; 12(7)2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-39065039

RESUMO

Vandammella animalimorsus is a Gram-negative and non-motile bacterium typically transmitted to humans through direct contact with the saliva of infected animals, primarily through biting, scratches, or licks on fractured skin. The absence of a confirmed post-exposure treatment of V. animalimorsus bacterium highlights the imperative for developing an effective vaccine. We intended to determine potential vaccine candidates and paradigm a chimeric vaccine against V. animalimorsus by accessible public data analysis of the strain by utilizing reverse vaccinology. By subtractive genomics, five outer membranes were prioritized as potential vaccine candidates out of 2590 proteins. Based on the instability index and transmembrane helices, a multidrug transporter protein with locus ID A0A2A2AHJ4 was designated as a potential candidate for vaccine construct. Sixteen immunodominant epitopes were retrieved by utilizing the Immune Epitope Database. The epitope encodes the strong binding affinity, nonallergenic properties, non-toxicity, high antigenicity scores, and high solubility revealing the more appropriate vaccine construct. By utilizing appropriate linkers and adjuvants alongside a suitable adjuvant molecule, the epitopes were integrated into a chimeric vaccine to enhance immunogenicity, successfully eliciting both adaptive and innate immune responses. Moreover, the promising physicochemical features, the binding confirmation of the vaccine to the major innate immune receptor TLR-4, and molecular dynamics simulations of the designed vaccine have revealed the promising potential of the selected candidate. The integration of computational methods and omics data has demonstrated significant advantages in discovering novel vaccine targets and mitigating vaccine failure rates during clinical trials in recent years.

3.
Comput Biol Med ; 178: 108738, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38870724

RESUMO

Neisseria meningitidis, commonly known as the meningococcus, leads to substantial illness and death among children and young adults globally, revealing as either epidemic or sporadic meningitis and/or septicemia. In this study, we have designed a novel peptide-based chimeric vaccine candidate against the N. meningitidis strain 331,401 serogroup X. Through rigorous analysis of subtractive genomics, two essential cytoplasmic proteins, namely UPI000012E8E0(UDP-3-O-acyl-GlcNAc deacetylase) and UPI0000ECF4A9(UDP-N-acetylglucosamine acyltransferase) emerged as potential drug targets. Additionally, using reverse vaccinology, the outer membrane protein UPI0001F4D537 (Membrane fusion protein MtrC) identified by subcellular localization and recognized for its known indispensable role in bacterial survival was identified as a novel chimeric vaccine target. Following a careful comparison of MHC-I, MHC-II, T-cell, and B-cell epitopes, three epitopes derived from UPI0001F4D537 were linked with three types of linkers-GGGS, EAAAK, and the essential PADRE-for vaccine construction. This resulted in eight distinct vaccine models (V1-V8). Among them V1 model was selected as the final vaccine construct. It exhibits exceptional immunogenicity, safety, and enhanced antigenicity, with 97.7 % of its residues in the Ramachandran plot's most favored region. Subsequently, the vaccine structure was docked with the TLR4/MD2 complex and six different HLA allele receptors using the HADDOCK server. The docking resulted in the lowest HADDOCK score of 39.3 ± 9.0 for TLR/MD2. Immune stimulation showed a strong immune response, including antibodies creation and the activation of B-cells, T Cytotoxic cells, T Helper cells, Natural Killer cells, and interleukins. Furthermore, the vaccine construct was successfully expressed in the Escherichia coli system by reverse transcription, optimization, and ligation in the pET-28a (+) vector for the expression study. The current study proposes V1 construct has the potential to elicit both cellular and humoral responses, crucial for the developing an epitope-based vaccine against N. meningitidis strain 331,401 serogroup X.


Assuntos
Vacinas Meningocócicas , Neisseria meningitidis , Neisseria meningitidis/imunologia , Neisseria meningitidis/genética , Humanos , Vacinas Meningocócicas/imunologia , Vacinologia/métodos , Genômica , Simulação por Computador , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/química , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito B/química , Epitopos de Linfócito B/genética
4.
Heliyon ; 10(9): e30393, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38711668

RESUMO

Hydroxychloroquine (HCQ) has gained significant attention as a therapeutic option for systemic lupus erythematosus (SLE) because of its multifaceted mechanism of action. It is a lipophilic, lysosomotropic drug, that easily traverses cell membranes and accumulates in lysosomes. Once accumulated, HCQ alkalizes lysosomes within the cytoplasm, thereby disrupting their function and interfering with processes like antigen presentation. Additionally, HCQ has shown potential in modulating T-cell responses, inhibiting cytokine production, and influencing Toll-like receptor signaling. Its immunomodulatory effects have generated interest in its application for autoimmune disorders. Despite its established efficacy, uncertainties persist regarding the optimal therapeutic concentrations and their correlation with adverse effects such as retinal toxicity. Therefore, standardized dosing and monitoring guidelines are crucial. In this study, we provide a comprehensive review of the mechanisms, efficacy, dosing variations, and retinal toxicity profiles of HCQ, which are essential to optimize SLE treatment protocols and ensure patient safety.

5.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-1010311

RESUMO

OBJECTIVE@#To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective.@*METHODS@#Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ+TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction.@*RESULTS@#TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45+ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01).@*CONCLUSIONS@#TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.


Assuntos
Masculino , Animais , Camundongos , Tripterygium , Psoríase/tratamento farmacológico , Queratinócitos , Dermatopatias/metabolismo , Citocinas/metabolismo , Imiquimode/metabolismo , Dermatite/patologia , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Pele/metabolismo
6.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1016377

RESUMO

@#The sternum is the pivotal component of the thoracic cavity. It is connected with the clavicle and ribs on the upper part and both sides respectively, and plays an important role in protecting the stability of the chest wall. Sternal resection usually results in a large segmental chest wall defect that causes the chest wall to float and requires sternal reconstruction. This paper reports a 62 years male patient with thymic squamous cell carcinoma with sternal metastasis, who underwent thymotomy, sternal tumor resection and autologous lilum graft combined with sternal reconstruction by titanium plate after relevant examination was completed and surgical contraindications were eliminated. The patient was followed up for 6 months, the respiratory and motor functions were normal and the thoracic appearance was good.

7.
Chinese Medical Ethics ; (6): 724-729, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1012969

RESUMO

With the rapid development of modern biomedicine, subjective factors such as human emotion and disease experience are diluted. Accurate data, programmed diagnosis and treatment process and other objective factors cut off the effective communication between doctors and patients, aggravating the already tense doctor-patient relationship and intensifying various conflicts in the clinic. In order to improve clinical humanistic care, medical and nursing workers have launched reflections and explorations. Narrative medicine is a new form of medical humanistic practice, while parallel chart, as an important way of its practice, records patients’ subjective experiences and painful feelings. It is of great theoretical significance and clinical value to sinicize narrative medicine and construct and promote parallel chart in Traditional Chinese Medicine (TCM) by studying the research progress of parallel chart in China and its application in TCM.

8.
Chinese Journal of School Health ; (12): 253-257, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1012515

RESUMO

Objective@#To investigate the effects of after school exercise service (referred to as the "after school ES") on physical health, so as to provide evidence for possible beneficial effect of after school ES.@*Methods@#Students in the fourth grade of primary school were recruited from September 2021 to July 2022 in Changsha City and divided into the control group ( n =220) and the after school ES group ( n =220). The control group only participated in the regular physical education activities of the school. The after school ES group received after school ES for one academic year, 4 times a week, 40-50 minutes per time, for a total of 32 weeks. Body shape indicators such as height, weight and percentage of body fat, as well as physical fitness indicators such as 50 meter running, grip strength and progressive aerobic cardiovascular endurance run (PACER) were measured in September to October 2021 and June to July 2022, respectively. Independent sample t-test, Chi square test and two factors repeated measurement analysis of variance were used for statistical analysis of the data.@*Results@#After one academic year, compared with the control group [(13.52±2.30)kg], muscle mass of primary school students in the after school ES group [(13.76±2.32)kg] significantly increased, while waist to hip ratio [(0.95±0.16)] and percentage of body fat [(20.17±7.43)%] significantly decreased compared to the control group [(1.01±0.21), (22.02±12.34)%]( F=330.70, 6.85, 4.33, P <0.05). The proportion of overweight and obesity in after school ES group decreased significantly from 19.5% to 12.3% ( χ 2=4.35, P <0.05). Compared with the control group, the scores of 50 meter running [(10.00±1.06, 10.21±0.83)s], 1 minute sit up [(33.25±8.24, 30.76±9.34)times], sitting and flexion [(14.53±7.50, 8.59±6.32)cm], 1 minute rope skipping [(125.01±30.50, 115.97±32.09)times], eyes closed and single legged standing [(30.00±34.72, 25.72±23.82)s], selective response time [(635.66±91.72, 652.79±120.42)ms] and VO 2max [(45.31± 1.02 , 43.67±0.85)mL/(kg〖 ·min)] in the after school ES group were significantly improved, with statistical significance ( F= 5.32 , 443.14, 97.23, 814.07, 36.49, 6.11, 396.91, P <0.05).@*Conclusions@#After school ES can improve body shape of primary school students, reduce the risk of overweight and obesity and enhance physical fitness. It is recommended that schools should appropriately increase after school ES to promote physical fitness of students.

9.
Cyberpsychol Behav Soc Netw ; 26(12): 924-929, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37883183

RESUMO

Amblyopia affects development of children's monocular vision and binocular function and becomes a largely intractable problem with increasing aging. This study is to investigate the binocular function and evaluate efficacy of digital therapy in children 8-13 years of age with anisometropic amblyopia. The patients in the digital therapy group performed the training with the digital amblyopia therapeutic software. The visual acuity and binocular function (perceptual eye position [PEP], suppression, and stereopsis) were examined at the first visit and 3-month post-treatment. Twenty-three cases in the control group and 25 cases in the digital therapy group were enrolled. The results revealed that 3-month digital therapy can effectively improve corrected distance visual acuity (CDVA) and improve the binocular function, including PEP, suppression, and second-order stereopsis in children with anisometropic amblyopia, 8-13 years of age. Digital therapy for amblyopia can effectively improve monocular CDVA of amblyopic eyes and binocular function in older children with anisometropic amblyopia.


Assuntos
Ambliopia , Criança , Humanos , Ambliopia/terapia , Visão Binocular , Acuidade Visual , Software
10.
Front Bioeng Biotechnol ; 11: 1209652, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37744250

RESUMO

The effects of the menstrual cycle and sex hormones on knee kinematics remain unclear. The purpose of the study was to investigate the effects of the menstrual cycle and serum sex hormone concentrations on knee kinematic parameters of the 90°cutting in female college soccer athletes. Three female college soccer teams (53 subjects) participated in the study. During the first menstrual cycle, a three-step method was used to exclude subjects with anovulatory and luteal phase-deficient (LPD) (12 subjects). The subjects' menstrual cycle was divided into the menstrual phase, late-follicular phase, ovulatory phase, and mid-luteal phase (group 1, 2, 3, 4). In each phase of the second menstrual cycle, we used a portable motion analysis system to enter the teams and tested the sex hormones concentrations and knee kinematics parameters in three universities in turn. We found that subjects had a lower maximum knee valgus in group 4 compared with other groups. This meant that subjects had a lower biomechanical risk of non-contact anterior cruciate ligament (ACL) injury in the mid-luteal phase. There was no significant correlation between serum estrogen, progesterone concentration, and knee kinematic parameters. This meant that sex hormones did not have a protective effect. Future studies need to incorporate more factors (such as neuromuscular control, etc.) to investigate.

11.
Biosci Biotechnol Biochem ; 87(8): 898-906, 2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-37363872

RESUMO

Epigallocatechin gallate (EGCG) and caffeine are inevitable to be ingested together in the process of drinking green tea. This study used Caenorhabditis elegans as an organism model to examine whether the binding of EGCG and caffeine could influence the fat-reduction effect. The results revealed that EGCG significantly reduced the Nile Red fluorescence intensity and the triglyceride/protein ratio of the C. elegans obesity model by 14.7% and 16.5%, respectively, while the effect of caffeine was not significant. Moreover, the degree of reduction in fluorescence intensity and triglyceride/protein ratio by EGCG + caffeine was comparable to that of EGCG. In the exploration of underlying mechanism, we found that EGCG and EGCG + caffeine treatments had no influence on food intake and energy expenditure of C. elegans. Their fat-reduction effects were dependent on the regulation of lipogenesis, as shown by the decreased expression of the sbp-1, fat-7, and daf-16 genes.


Assuntos
Cafeína , Catequina , Animais , Cafeína/farmacologia , Caenorhabditis elegans , Dieta , Chá/química , Catequina/farmacologia , Catequina/análise , Triglicerídeos , Glucose
12.
Heliyon ; 9(2): e13529, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36873162

RESUMO

The mechanical structure topology design based on substructure always adopts the traditional substructure design method, which often comes from the experience and is limited by the inherent or stereotyped design thinking. A substructure design method based on biological unit cell (UC) is proposed, which draws inspiration from the biological efficient load-bearing topology structure. Especially, the thought of the formalized problem-solving of extension matter-element is introduced. Through the matter-element definition of UC substructure, the process model for the structure bionic topology design method based on biological UC is formed, which avoids the random or wild mental stimulation of the structure topology design method based on traditional substructure. In particular, in this proposed method, aiming at the problem about how to achieve the integration of high-efficiency load-bearing advantage of different organisms, furthermore, a biological UC hybridization method based on the principle of inventive problem solving theory (TRIZ) is proposed. The typical case is used to illustrate the process of this method in detail. The results from simulations and experiments both show that: the load-bearing capacity of structure design based on biology UC is improved than the initial design; on this basis, the load-bearing capacity of structure design is improved further through UC hybridization. All these show the feasibility and correctness of the proposed method.

13.
Food Chem ; 412: 135417, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-36753940

RESUMO

Stable isotope and multi-element analytical techniques with chemometrics were developed to trace the origin authenticity of rice in China market. In the long-term study from 2017 to 2020, a total of 115 batches of rice samples from 8 main producing areas of 7 Asian countries were determined 5 stable isotope ratios and 18 elemental contents. One-way analysis of variance (ANOVA) and various multivariate modeling methods were performed for the origin discrimination. Supervised multivariate modeling including partial least squares discriminant analysis (PLS-DA) and linear discriminant analysis (LDA) can realize more satisfactory identification of 8 rice origins than ANOVA comparison and unsupervised methods, their leave-one-out cross-validation accuracies approach 85.0 % and 90.9 %, respectively. δ2H, δ13C, Ba, Al, Mg, δ34S, Pb and δ18O were screened as the most important variables for rice origin traceability (VIP > 1 or AUC > 0.5). This analytical strategy combining maybe promising to ensure the origin authenticity and combat illegal mislabeling in rice trade.


Assuntos
Oryza , Isótopos/análise , Ásia , China , Análise Discriminante
14.
Nat Prod Res ; 37(15): 2517-2524, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35319322

RESUMO

A new oleanane-type triterpene, ardisiapunine A (1), together with eight known compounds were isolated from the roots of Ardisia lindleyana D.Dietr. Their chemical structures were determined by means of spectroscopic methods including HR-ESI-MS and (1 D, 2 D) NMR data. The absolute configuration of compound 1 was established by a single-crystal X-ray diffraction experiment. The new compound is an unusual oleanane-type triterpene bearing an acetal and a C-13-C-18 double bond. The cytotoxicity of all isolated compounds were evaluated using four human cancer cell lines, including A549, HepG2, HeLa and U87. The new compound 1 and compound 2 were weakly active but the known compound 6 exhibited a high cytotoxicity compared to cisplatin.


Assuntos
Antineoplásicos Fitogênicos , Antineoplásicos , Ardisia , Saponinas , Triterpenos , Humanos , Ardisia/química , Triterpenos/farmacologia , Triterpenos/química , Estrutura Molecular , Células HeLa , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Saponinas/química
15.
Prep Biochem Biotechnol ; 53(3): 308-316, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35670651

RESUMO

Purification of total flavonoids from Ginkgo biloba flowers (GBF) extracts were studied using six resins. Adsorption-desorption experiments indicated that polyamide resin is the most suitable resin. The optimal purification process of total flavonoids of GBF was as follows: a loading concentration of 5.85 mg/mL, a loading volume of 1 bed volume (BV), a loading flow rate of 2 BV/h, a water volume of 2.67 BV, and a desorption solution of 40% ethanol. Under these conditions, the maximum purity of total flavonoids was 37.1 ± 1.1%. The antioxidant activity of purified flavonoids was further evaluated in vitro. It showed that the 40% ethanol purified fraction (Fr. B) group had the strongest antioxidant activity of the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity concentration for 50% of maximal effect (EC50, 145.4 ± 13.8 µg/mL) and ferric reducing ability (2.5 ± 0.2 mM FeSO4 equivalent mg-1 Fr. B). In addition, at the concentration of 160 µg/mL, the Fr. B strikingly increased the viability rate of hydrogen peroxide stimulated PC-12 cells to normal levels (***p < 0.001). This method provides a basis for the application and development of GBF resources. It indicated that the purified GBF flavonoids can be used as a source of potential antioxidant.


Assuntos
Flavonoides , Ginkgo biloba , Flavonoides/farmacologia , Flavonoides/química , Ginkgo biloba/química , Antioxidantes/farmacologia , Antioxidantes/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Cromatografia , Flores
16.
Brain Imaging Behav ; 17(1): 90-99, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36417126

RESUMO

To explore the relationship between cognitive function and blood-brain barrier leakage in non-brain metastasis lung cancer and healthy controls. 75 lung cancers without brain metastasis and 29 healthy controls matched with age, sex, and education were evaluated by cognitive assessment, and the Patlak pharmacokinetic model was used to calculate the average leakage in each brain region according to the automated anatomical labeling atlas. After that, the relationships between cognitive and blood-brain barrier leakage were evaluated. Compared with healthy controls, the leakage of bilateral temporal gyrus and whole brain gyrus were higher in patients with lung cancers (P < 0.05), mainly in patients with advanced lung cancer (P < 0.05), but not in patients with early lung cancer (P > 0.05). The cognitive impairment of advanced lung cancers was mainly reflected in the damage of visuospatial/executive, and delayed recall. The left temporal gyrus with increased blood-brain barrier leakage showed negative correlations with delayed recall (r = -0.201, P = 0.042). An increase in blood-brain barrier leakage was found in non-brain metastases advanced lung cancers that corresponded to decreased delayed recall. With progression in lung cancer staging, blood-brain barrier shows higher leakage and may lead to brain metastases and lower cognitive development.


Assuntos
Disfunção Cognitiva , Neoplasias Pulmonares , Humanos , Barreira Hematoencefálica , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/patologia , Cognição , Neoplasias Pulmonares/diagnóstico por imagem
17.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-981380

RESUMO

The chemical compositions of Rodgersia aesculifolia were isolated and purified using a combination of silica gel, reverse phase silica gel, Sephadex LH-20 column chromatography, and semi-preparative HPLC. The structures were determined according to the physicochemical properties and spectroscopic data. The MTT method and the ABTS kit were used to measure the cytotoxicity and antioxidant capacity of all isolates, respectively. Thirty-four compounds were isolated from R. aesculifolia and elucidated as stigmastane-6β-methoxy-3β,5α-diol(1), stigmastane-3β,5α,6β triol(2), β-sitosterol(3), β-daucosterol(4), stigmast-4-en-3-one(5), bergenin(6), 11-β-D-glucopyranosyl-bergenin(7), 11-O-galloybergenin(8), 1,4,6-tri-O-galloyl-β-D-glucose(9), gallic acid(10), 3,4-dihydroxybenzoic acid methyl ester(11), ethyl gallate(12), ethyl 3,4-dihydroxybenzoate(13), caffeic acid ethyl ester(14), p-hydroxybenzeneacetic acid(15), 4-hydroxybenzoic acid(16), 2,3-dihydroxy-1-(4-hydroxy-3-methoxyphenyl)-propan-1-one(17), 3,7-dimethyl-2-octene-1,7-diol(18), crocusatin-B(19), neroplomacrol(20), geniposide(21), 3-hydroxyurs-12-en-27-oic acid(22), 3β-trans-p-coumaroyloxy-olean-12-en-27-oic acid(23), aceriphyllic acid G(24), isolariciresinol(25), trans-rodgersinine B(26), cis-rodgersinine A(27), neo-olivil(28),(7S,8R)-dihydro-3'-hydroxy-8-hydroxy-methyl-7-(4-hydroxy-3-methoxy phenyl)-1'-benzofuranpropanol(29), 5,3',4'-trihydroxy-7-methoxyflavanone(30), quercetin 3-rutinoside(31), catechin-[8,7-e]-4β-(3,4-dihydroxy-phenyl)-dihydro-2(3H)-pyranone(32), ethyl α-L-arabino-furanoside(33), and l-linoleoylglycerol(34). One new compound was discovered(compound 1), 25 compounds were first isolated from R. aesculifolia, and 22 compounds were first isolated from the Rodgersia plant. The results indicated that compounds 22-24 possessed cytotoxicity for HepG2, MCF-7, HCT-116, BGC-823, and RAFLS cell lines(IC_(50) ranged from 5.89 μmol·L~(-1) to 20.5 μmol·L~(-1)). Compounds 8-14 and 30-32 showed good antioxidant capacity, and compound 9 showed the strongest antioxidant activity with IC_(50) of(2.00±0.12) μmol·L~(-1).


Assuntos
Antioxidantes/análise , Sílica Gel/análise , Raízes de Plantas/química
18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-981310

RESUMO

This study explored the molecular mechanism of acteoside against hepatoma 22(H22) tumor in mice through c-Jun N-terminal kinase(JNK) signaling pathway. H22 cells were subcutaneously inoculated in 50 male BALB/c mice, and then the model mice were classified into model group, low-dose, medium-dose, and high-dose acteoside groups, and cisplatin group. The administration lasted 2 weeks for each group(5 consecutive days/week). The general conditions of mice in each group, such as mental status, diet intake, water intake, activity, and fur were observed. The body weight, tumor volume, tumor weight, and tumor-inhibiting rate were compared before and after administration. Morphological changes of liver cancer tissues were observed based on hematoxylin and eosin(HE) staining, and the expression of phosphorylated(p)-JNK, JNK, B-cell lymphoma-2(Bcl-2), Beclin-1, and light chain 3(LC3) in each tissue was detected by immunohistochemistry and Western blot. qRT-PCR was performed to detect the mRNA expression of JNK, Bcl-2, Beclin-1, and LC3. The general conditions of mice in model and low-dose acteoside groups were poor, while the general conditions of mice in the remaining three groups were improved. The body weight of mice in medium-dose acteoside group, high-dose acteoside group, and cisplatin group was smaller than that in model group(P<0.01). The tumor volume in model group was insignificantly different from that in low-dose acteoside group, and the volume in cisplatin group showed no significant difference from that in high-dose acteoside group. Tumor volume and weight in medium-dose and high-dose acteoside groups and cisplatin group were lower than those in the model group(P<0.001). The tumor-inhibiting rates were 10.72%, 40.32%, 53.79%, and 56.44% in the low-dose, medium-dose, and high-dose acteoside groups and cisplatin group, respectively. HE staining showed gradual decrease in the count of hepatoma cells and increasing sign of cell necrosis in the acteoside and cisplatin groups, and the necrosis was particularly obvious in the high-dose acteoside group and cisplatin group. Immunohistochemical results suggested that the expression of Beclin-1, LC3, p-JNK, and JNK was up-regulated in acteoside and cisplatin groups(P<0.05). The results of immunohistochemistry, Western blot, and qRT-PCR indicated that the expression of Bcl-2 was down-regulated in the medium-dose and high-dose acteoside groups and cisplatin group(P<0.01). Western blot showed that the expression of Beclin-1, LC3, and p-JNK was up-regulated in acteoside and cisplatin groups(P<0.01), and there was no difference in the expression of JNK among groups. qRT-PCR results showed that the levels of Beclin-1 and LC3 mRNA were up-regulated in the acteoside and cisplatin groups(P<0.05), and the level of JNK mRNA was up-regulated in medium-dose and high-dose acteoside groups and cisplatin group(P<0.001). Acteoside promotes apoptosis and autophagy of H22 cells in mice hepatoma cells by up-regulating the JNK signaling pathway, thus inhibiting tumor growth.


Assuntos
Masculino , Animais , Camundongos , Cisplatino/farmacologia , Carcinoma Hepatocelular/genética , Sistema de Sinalização das MAP Quinases , Proteína Beclina-1 , Apoptose , Neoplasias Hepáticas/genética , Necrose , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Linhagem Celular Tumoral , RNA Mensageiro/metabolismo , Autofagia
19.
Acta Physiologica Sinica ; (6): 255-268, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-981003

RESUMO

Cerebral hypoxia often brings irreversible damage to the central nervous system, which seriously endangers human health. It is of great significance to further explore the mechanism of hypoxia-associated brain injury. As a programmed cell death, ferroptosis mainly manifests as cell death caused by excessive accumulation of iron-dependent lipid peroxides. It is associated with abnormal glutathione metabolism, lipid peroxidation and iron metabolism, and is involved in the occurrence and development of various diseases. Studies have found that ferroptosis plays an important role in hypoxia-associated brain injury. This review summarizes the mechanism of ferroptosis, and describes its research progress in cerebral ischemia reperfusion injury, neonatal hypoxic-ischemic brain damage, obstructive sleep apnea-induced brain injury and high-altitude hypoxic brain injury.


Assuntos
Humanos , Recém-Nascido , Ferroptose , Apoptose , Hipóxia-Isquemia Encefálica , Lesões Encefálicas , Ferro , Traumatismo por Reperfusão
20.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-986930

RESUMO

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.


Assuntos
Feminino , Humanos , Adolescente , SARS-CoV-2 , Olfato , COVID-19/complicações , Estudos Transversais , Vacinas contra COVID-19 , Incidência , Transtornos do Olfato/etiologia , Distúrbios do Paladar/etiologia , Prognóstico
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