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1.
Am J Case Rep ; 25: e943777, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38973145

RESUMO

BACKGROUND Amlodipine, a calcium channel blocker, and atenolol, a beta blocker, are commonly used as a fixed drug combination (FDC) to treat hypertension. Intentional or non-intentional overdose of amlodipine-atenolol results in hypotension and myocardial depression with a high risk of mortality. This report describes a 64-year-old man with an overdose of amlodipine-atenolol, presenting as an emergency with hypotension, bradycardia, and severe metabolic acidosis. He was successfully treated with intravenous calcium chloride infusion, hyperinsulinemia euglycemia therapy (HIE), and continuous veno-venous hemodialysis (CVVHD). CASE REPORT A 64-year-old man was diagnosed with essential hypertension 1 week prior to the admission. He had been prescribed 1 FDC tablet of amlodipine and atenolol (5+50 mg) per day; however, he took 1 table of the FDC per day for 3 days and then took 3-4 tablets each day during the next 4 days. He was brought to the hospital with hypotension, bradycardia, and severe metabolic acidosis and was diagnosed with amlodipine-atenolol overdose. He was treated with intravenous calcium chloride infusion, HIE, and CVVHD. His hemodynamics started to improve after administering these therapies for 6 h. Inotropes were gradually tapered off and stopped. He was extubated on day 5 and recovered completely. CONCLUSIONS This report shows the serious effects amlodipine-atenolol overdose and the challenges of emergency patient management. An overdose of FDC of amlodipine and atenolol can cause cardiovascular collapse and severe metabolic acidosis. Timely and aggressive management with intravenous calcium infusion, HIE, and CVVHD is essential.


Assuntos
Anlodipino , Atenolol , Bloqueadores dos Canais de Cálcio , Overdose de Drogas , Humanos , Masculino , Anlodipino/intoxicação , Pessoa de Meia-Idade , Overdose de Drogas/terapia , Atenolol/intoxicação , Bloqueadores dos Canais de Cálcio/intoxicação , Terapia de Substituição Renal Contínua , Infusões Intravenosas , Cloreto de Cálcio/intoxicação , Cloreto de Cálcio/administração & dosagem , Anti-Hipertensivos/intoxicação , Anti-Hipertensivos/uso terapêutico , Combinação de Medicamentos
2.
Artigo em Inglês | MEDLINE | ID: mdl-38980897

RESUMO

Despite the remarkable advances of dermal fillers that reduce wrinkles caused by dermis thickness reduction, they still lack effective hydrogel systems that stimulate collagen generation along with injection convenience. Here, we develop a stem cell-derived extracellular vesicle (EV)-bearing thermosensitive hydrogel (EVTS-Gel) for effective in vivo collagen generation. The TS-Gel undergoes sol-gel transition at 32.6 °C, as demonstrated by the storage and loss moduli crossover. Moreover, the TS-Gel and the EVTS-Gel have comparable rheological properties. Both hydrogels are injected in a sol state; hence, they require lower injection forces than conventional hydrogel-based dermal fillers. When locally administered to mouse skin, the TS-Gel extends the retention time of EVs by 2.23 times. Based on the nature of the controlled EV release, the EVTS-Gel significantly inhibits the dermis thickness reduction caused by aging compared to the bare EV treatment for 24 weeks. After a single treatment, the collagen layer thickness of the EVTS-Gel-treated dermis becomes 2.64-fold thicker than that of the bare EV-treated dermis. Notably, the collagen generation efficacy of the bare EV is poorer than that of the EVTS-Gel of a 10× lesser dose. Overall, the EVTS-Gel shows potential as an antiaging dermal filler for in vivo collagen generation.

3.
J Invertebr Pathol ; 206: 108164, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38960029

RESUMO

This study aims to investigate how bioactivities of the coral surface mucus layer (SML) respond to changes in mucus-associated bacterial communities between bleached and healthy Porites lobata corals in Nha Trang Bay, Vietnam. The findings suggested that significant shifts in the mucus-associated bacterial communities were related to changes in coral health states from bleached to healthy P. lobata colonies (p < 0.05), while bacterial compositions were not significantly different across seasons and locations (p > 0.05). Of which 8 genera, Shewanella, Fusibacter, Halodesulfovibrio, Marinifilum, Endozoicomonas, Litoribacillus, Algicola, and Vibrio were present only in the SML of bleached coral while absent in the SML of the healthy one. As compared with the bleached SML, the healthy SML demonstrated stronger antibacterial activity against a coral bleaching pathogen, V. coralliilyticus, higher antitumor activity against HCT116 cell accompanied with increased induction of cleaved PARP and accelerated cell nucleic apoptosis and cycle arrest at S and G2/M phases exhibiting several typical characteristics, cell shrinkage, lost cell contact, and apoptotic body formation. Moreover, putative compounds detected at 280 nm in the healthy SML were obviously higher than those in the bleached one, probably they could be bioactive molecules responsible for competitively exclusion of pathogens, Algicola and Vibrio, from the healthy SML.

4.
Isotopes Environ Health Stud ; : 1-25, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38973646

RESUMO

Radioactivity in coastal sediments in northern Vietnam was examined using data from five sediment cores to assess radioactivity concentrations and radiation risk indices. Radiation risk indices included radium equivalent activity (Raeq), the absorbed dose rate (ADR), the annual effective dose equivalent (AEDE), the activity utilization index (AUI), the external hazard index (Hex), the representative level gamma index (Iγr), and the annual gonadal effective dose rate (AGDE). The radioactivity concentrations of 40K, 232Th, 226Ra, 238U, and 137Cs were 567, 56.1, 35.1, 37.9, and 1.18 Bq/kg, respectively. The average concentrations of 40K, 232Th, 226Ra, and 238U were above the global average at five sites, except for 137Cs, which was low. The Raeq, Hex, and AUI indices were below the recommended values, while the AEDE, ADR, AGDE, and Iγr indices were above the recommended values. Moreover, 40K, 232Th, 226Ra, and 238U had significant impacts on the radiation hazard indices Raeq, ADR, AEDE, Iγr, AUI, Hex, and AGDE. There are three coastal sediment groups on the northern coast of Vietnam: Group 1 has a higher radioactivity and radiation risk index than Group 2 but a lower value than Group 3. Group 3 had the highest radioactivity and radiation risk index. The values of 40K, 232Th, 226Ra, and 238U and the ADR, AUI, Iγr, and AGDE indices in the sediment threaten the living environment.

5.
Front Microbiol ; 15: 1394998, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38933021

RESUMO

In this study, we discuss for the first time the relationships between the diversity of the bacterial population and of the metals and metalloids concentrations in the sediments of the Red River Delta, Vietnam. The analysis of the 16S rRNA by the Illumina technology revealed a diversified population and a potential of bioremediation by the microorganisms, notably by the Bacilli relatively abundant in the Bach Dang estuary, where high metals and metalloids concentrations were highlighted. This work offers new information on the environmental context of the delta and highlights the potential impact that metals and metalloids may have on the bacterial population. Further investigations on the role of the bacteria in the biogeochemistry of this ecosystem will be of interest for the development of bioremediation processes.

6.
PLoS One ; 19(6): e0305869, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38913676

RESUMO

BACKGROUND: This study aimed to measure the preferences for mental health support among health professionals, their willingness to support the mental health of colleagues and associated factors. METHOD: A descriptive cross-sectional study was performed from August to October 2022 within five hospitals located in Hanoi, Vietnam. A total of 244 health professionals participated in the study. Data on socio-economic status, health and COVID-19-related characteristics, Depression Anxiety Stress Scale (DASS-21); and preferences for mental health support services were collected by using a structured self-reported questionnaire. Multivariate logistic regression models were utilized to identify associated factors with the demand for mental support services. RESULTS: 13.9%, 17.1% and 8.6% reported having at least mild depression, anxiety and stress, respectively. There 13.9% did not seek any mental health support during the COVID-19 pandemic. The most common support included talking with friends (52.9%), family (50.8%), colleagues (47.6%) and using social networks/Internet (43.5%). There 31.1% had been aware of mental health services, but only 18.0% used this service at least once. Regarding preferences, 47.3% had a demand for mental support services, and the most preferred service was providing coping skills (25.9%), followed by skills to support others against mental problems (22.2%). Major sources of support included psychiatrists (34.4%), colleagues (29.1%) and family (27.9%). The main preferred channels for support included telephone/mobile phone (35.7%) and Internet (20.9%). Only 12.3% were willing to provide mental support for colleagues during the pandemic. Age, education, perceived mental health status, ever seeking any mental service, and DASS-21 depression score were associated with demand for mental support services. CONCLUSION: This study found a lack of awareness of mental health services for health professionals, as well as moderate levels of demand for this service in this population. Raising awareness and developing tailored mental health support services are important to enhancing the mental well-being of health professionals in Vietnam to prepare for the next pandemic.


Assuntos
COVID-19 , Depressão , Pessoal de Saúde , Serviços de Saúde Mental , Saúde Mental , Humanos , COVID-19/epidemiologia , COVID-19/psicologia , Vietnã/epidemiologia , Masculino , Feminino , Adulto , Estudos Transversais , Pessoal de Saúde/psicologia , Pessoa de Meia-Idade , Depressão/epidemiologia , Ansiedade/epidemiologia , Pandemias , Inquéritos e Questionários , SARS-CoV-2 , Estresse Psicológico/epidemiologia , Apoio Social
7.
Vet World ; 17(5): 940-945, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38911090

RESUMO

Background and Aim: Probiotics are used at different stages of gestation to promote reproductive performance in sows. This study investigated the effect of Bacillus subtilis QST 713 supplementation during late gestation in multiparous sows on different reproductive parameters. Materials and Methods: On day 85 of gestation, 115 multiparous healthy Landrace Yorkshire sows were randomly assigned to two groups with equal parity numbers. The control group (58 sows) was fed with basal diets, and the probiotic group (57 sows) was fed with basal diets +1010 colony-forming unit (CFU) B. subtilis QST 713 from day 85 to parturition. Back fat thickness on days 85 and 110, number of total born, number of born alive, stillbirth and mummy rates, individual birth weight, litter birth weight, within-litter variation of piglet birth weight, and postpartum vaginal discharge duration were recorded and compared between the two groups. Results: The number of total born, number born alive, back fat thickness of sows before farrowing, litter weight, within-litter variation of piglet birth weight, and postpartum vaginal discharge duration were similar in both groups (p > 0.05). Dietary supplementation with B. subtilis QST 713 decreased the stillbirth rate (3.96 vs. 6.39%, p = 0.046) and born dead rate (5.12 vs. 8.57%, p = 0.035) and increased the birth weight of piglets (1552.78 vs. 1506.15 g, p = 0.049). Conclusion: Daily supplementation with 1010 CFU of B. subtilis QST 713 during late gestation in multiparous sows could increase reproductive performance by increasing birth weight and decreasing stillbirth rate.

8.
J Environ Radioact ; 277: 107445, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38820672

RESUMO

Transfer of natural radionuclides from soil to water spinach (Ipomoea aquatica Forssk) in Hanoi, Vietnam have been investigated using a low background gamma spectrometer with an HPGe detector (Model-GC5019). Twenty pairs of soil and water spinach samples in two environmental conditions, i.e., flooded and unflooded, were collected for measuring the activity concentrations and determining the soil-to-plant transfer factors (TFs) of natural radionuclides. For water spinach, stems and leaves were collected as the main parts for human consumption and livestock food. The TF of 40K is within the range of 0.32-2.49, which is greater than that of 228Ra (0.01-0.17) and 226Ra (0.01-0.13). The geometric means (geometric standard deviations) of the TFs are 1.17(1.89), 0.05(2.41) and 0.04(1.88) for flooded sites, and 0.89(1.73), 0.03(2.12) and 0.03(1.82) for unflooded sites, respectively. Comparing between the flooded and unflooded sites, the TFs are all greater at the flooded sites.


Assuntos
Ipomoea , Monitoramento de Radiação , Poluentes Radioativos do Solo , Vietnã , Monitoramento de Radiação/métodos , Ipomoea/química , Poluentes Radioativos do Solo/análise , Solo/química , Inundações , Poluentes Radioativos da Água/análise
9.
BMC Infect Dis ; 24(1): 508, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773469

RESUMO

Chromobacterium violaceum is a rare but severe and often fatal cause of disease in humans. We present 2 clinical cases of sepsis and skin abscesses / cellulitis caused by C. violaceum seen in a referral hospital for infectious diseases in Vietnam. Both patients survived, but appropriate antibiotic treatment was only installed after culture of the organism. We reviewed and summarised the characteristics of C. violaceum infection and treatment.


Assuntos
Antibacterianos , Chromobacterium , Infecções por Bactérias Gram-Negativas , Feminino , Humanos , Antibacterianos/uso terapêutico , Celulite (Flegmão)/microbiologia , Celulite (Flegmão)/tratamento farmacológico , Chromobacterium/isolamento & purificação , Chromobacterium/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Sepse/microbiologia , Sepse/tratamento farmacológico , Vietnã , Criança , Adolescente
10.
Int J Surg Case Rep ; 118: 109603, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38642432

RESUMO

INTRODUCTION AND IMPORTANCE: Abdominal ectopic pregnancy (AEP) located at hepatic region and pelvic-wall ectopic pregnancy (EP) are rare entities, that provoking a potentially life-threatening condition. Due to insufficient data, a proper management of non-specific types remains a challenge for all gynecologists worldwide. CASE PRESENTATION: Two child-bearing age women were hospitalized due to delayed menstruation and a urine pregnancy test was positive without a determination of intrauterine pregnancy. The first EP case was located at the pelvic wall which identified incidentally during laparoscopy for a presumed tubal ectopic pregnancy on ultrasonography throughout. The second EP case was found at the hepatic region due to intermittent pain rising from the right upper quadrant region and serial ultrasonic findings. In our management, both cases were successfully assessed by laparoscopy and laparotomy without requiring further intervention, respectively. CLINICAL DISCUSSION: An accurate diagnosis of EP location at liver and pelvic wall is totally difficult since its uncommon location. An initial assessment should be based on clinical symptoms and the treatment remains controversial. The surgical management including laparotomy and laparoscopy depends on clinical evaluation, experience of surgeon, and interdisciplinary team. Thus, these abnormal sites of ectopic pregnancy ought to take into consideration for all gynecologists in an emergency condition with a major hemorrhage. CONCLUSIONS: In reproductive age women, primary EP at liver and pelvic wall should be considered with high index of suspicion if intrauterine pregnancy is totally excluded. Timely diagnosis, rational management by surgical excision, and a multidisciplinary team can reduce substantially adverse outcomes.

11.
Turk J Ophthalmol ; 54(2): 83-89, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38645613

RESUMO

Objectives: To review the current literature related to the correlation between translaminar pressure difference (TLPD) and glaucoma. Materials and Methods: In this article, we conducted a literature review using MEDLINE via PubMed, Cochrane Eyes and Vision, and Google Scholar from 01/01/2010 to 31/12/2022. Search terms included "glaucoma", "intraocular pressure", "translaminar cribrosa pressure gradient/difference", "intracranial pressure", and "cerebrospinal fluid pressure". Of 471 results, 8 articles were selected for the meta-analysis. Results: Our meta-analysis demonstrated significantly higher intraocular pressure, lower cerebrospinal fluid pressure (CSFp), and greater TLPD in high-tension and normal-tension glaucoma groups compared to healthy groups. Conclusion: The differences in CSFp and TLPD between glaucoma and healthy people detected in current studies suggests a potential relationship between TLPD and glaucoma.


Assuntos
Pressão Intraocular , Doenças do Nervo Óptico , Humanos , Pressão Intraocular/fisiologia , Doenças do Nervo Óptico/diagnóstico , Doenças do Nervo Óptico/etiologia , Doenças do Nervo Óptico/fisiopatologia , Pressão do Líquido Cefalorraquidiano/fisiologia , Glaucoma/fisiopatologia , Tonometria Ocular , Glaucoma de Baixa Tensão/fisiopatologia , Glaucoma de Baixa Tensão/diagnóstico
12.
J Pharm Pract ; : 8971900241248481, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627957

RESUMO

Background: Headache is a debilitating complication following an aneurysmal subarachnoid hemorrhage (aSAH). Despite its impact on morbidity and quality of life, limited evidence characterizes the effectiveness of opioids. Objective: The aim of this study was to evaluate opioid associated reduction in pain scores in patients with aSAH-associated headache. Methods: This is a retrospective study of adult patients with an aSAH, Hunt and Hess grades I - III, admitted to a neurosciences intensive care unit. Descriptive and inferential statistics were used to characterize headache treatment strategies and opioid associated reduction in pain scores. Results: Opioids were used in up to 97.6% of patients for the management of aSAH-associated headache. Median reduction in pain after opioid administration was -1 (IQR: -3-0). Correlation between opioid dose and change in pain scores was negligible (rs = .01). Overall, 68.8% of patients were discharged on an opioid analgesic with predictive factors being severe headache (OR 2.52; 1.04 - 6.14) and oral morphine milligram equivalents ≥60 mg per day during the hospital stay (OR 3.02; 1.22 - 7.47). Conclusions: Opioids were associated with a small reduction in pain when assessed via the NRS. An increased opioid dose did not correlate with a greater reduction in assessed pain scores. A high percentage of patients remained on opioids throughout hospitalization and were eventually discharged on an opioid. The impact of discharge opioid prescriptions and risk of opioid persistence creates a cause for concern. It is imperative that we seek improved pain management strategies for aSAH-associated headache.

13.
Biomolecules ; 14(3)2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38540666

RESUMO

Pathogenic platelet factor 4 (PF4) antibodies contributed to the abnormal coagulation profiles in COVID-19 and vaccinated patients. However, the mechanism of what triggers the body to produce these antibodies has not yet been clarified. Similar patterns and many comparable features between the COVID-19 virus and heparin-induced thrombocytopenia (HIT) have been reported. Previously, we identified a new mechanism of autoimmunity in HIT in which PF4-antibodies self-clustered PF4 and exposed binding epitopes for other pathogenic PF4/eparin antibodies. Here, we first proved that the SARS-CoV-2 spike protein (SP) also binds to PF4. The binding was evidenced by the increase in mass and optical intensity as observed through quartz crystal microbalance and immunosorbent assay, while the switching of the surface zeta potential caused by protein interactions and binding affinity of PF4-SP were evaluated by dynamic light scattering and isothermal spectral shift analysis. Based on our results, we proposed a mechanism for the generation of PF4 antibodies in COVID-19 patients. We further validated the changes in zeta potential and interaction affinity between PF4 and SP and found that their binding mechanism differs from ACE2-SP binding. Importantly, the PF4/SP complexes facilitate the binding of anti-PF4/Heparin antibodies. Our findings offer a fresh perspective on PF4 engagement with the SARS-CoV-2 SP, illuminating the role of PF4/SP complexes in severe thrombotic events.


Assuntos
COVID-19 , Trombocitopenia , Humanos , Anticorpos Monoclonais Humanizados , Fatores Imunológicos , Fator Plaquetário 4/química , Fator Plaquetário 4/metabolismo , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus
14.
Chem Biol Drug Des ; 103(3): e14496, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38444006

RESUMO

Chitooligosaccharide (COS) is a derivative of chitosan, which is a natural macromolecular compound. COS has been shown effects in an inflammatory response. Recent reports show that COS derivatives have enhanced anti-inflammatory activity by inhibiting intracellular signals. Evaluation of the anti-inflammatory effect of caffeic acid conjugated COS chain (CA-COS) was performed in this study. The effects of CA-COS on the inflammatory response were demonstrated in lipopolysaccharide-stimulated RAW264.7 macrophages. The results showed that CA-COS inhibited nitric oxide (NO) production and downregulated the gene expression of nitric oxide synthase (iNOS), and cytokines such as tumor necrosis factor-alpha (TNF-α), IL-1ß, and IL-6 without cytotoxic effect. In addition, western blot analysis showed that CA-COS inhibits the protein expression of iNOS and nuclear factor kappa B (NF-kB), including p50 and p65, and mitogen-activated protein kinase (MAPK) signaling pathways. Collectively, these results provide clear evidence for the anti-inflammatory mechanism of CA-COS that show great potential as a novel agent for the prevention and therapy of inflammatory diseases.


Assuntos
Ácidos Cafeicos , Quitosana , Proteínas Quinases Ativadas por Mitógeno , NF-kappa B , Oligossacarídeos , Quitina/farmacologia , Anti-Inflamatórios/farmacologia
15.
Artigo em Inglês | MEDLINE | ID: mdl-38226566

RESUMO

A mesophilic, anaerobic, endospore-forming, fermentative bacterium designated strain 8C15bT was isolated from bank sediment of the Bach Dang Estuary, Haiphong, Vietnam. The Bach Dang Estuary, where Haiphong harbour is located, is subject to strong anthropogenic influence, resulting in high concentrations of black carbon and heavy metals. Strain 8C15bT grew optimally at 30 °C, pH 7.5 and with 2.5 % (w/v) NaCl. The main cellular fatty acids consisted of iso-C15 : 0 (51 %), iso-C15:1 ω7c (32 %) and iso-C13 : 0 (5 %). Genomic considerations of strain 8C15bT and comparisons with the phylogenetically closest strains of the genus Tepidibacter provide evidence that Tepidibacter thalassicus SC562T (=DSM 15285T), Tepidibacter formicigenes DV1184T (=DSM 15518T), Tepidibacter mesophilus B1T (=JCM 16806T) and strain 8C15bT could be differentiated at the species level. We propose the name Tepidibacter aestuarii sp. nov. for the type strain 8C15bT (=JCM 35983T=KCTC 25692T). Finally, the nickel-tolerance properties of strain 8C15bT are highlighted in this study.


Assuntos
Estuários , Ácidos Graxos , Ácidos Graxos/química , Vietnã , Análise de Sequência de DNA , Filogenia , Composição de Bases , DNA Bacteriano/genética , RNA Ribossômico 16S/genética , Técnicas de Tipagem Bacteriana , Fosfolipídeos/química
16.
Int J Emerg Med ; 17(1): 14, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38287235

RESUMO

BACKGROUND: Cardiopulmonary collapse is a catastrophic event in cesarean section, which leads to adverse outcomes for both the mother and the fetus. Pulmonary embolism is one of the rare etiologies of this entity. We herein reported the successful management of acute embolism pulmonary associated with cesarean delivery on a healthy pregnant woman at our tertiary referral hospital. CASE PRESENTATION: A full-term pregnant woman hospitalized for planned cesarean delivery due to placenta previa without cardiorespiratory diseases. She was scheduled uneventfully for a planned cesarean section. After placental delivery, the patient spontaneously fell into cardiopulmonary collapse and her vital signs deteriorated rapidly. The obstetricians promptly completed the cesarean section and performed all procedures to prevent the PPH and preserve the uterus. At the same time, the anesthesiologists continued to carry out advanced heart-lung resuscitation in order to control her vital signs. After surgery, the multidisciplinary team assessed the patient and found a thrombus in her pulmonary circulation. Therefore, the patient was managed with therapeutic anticoagulation. The patient recovered in good clinical condition and was discharged after 2 weeks without any complications. CONCLUSIONS: The diagnosis of acute pulmonary embolism is extremely difficult due to uncommon occurrence, sudden onset, and non-specific presentation. Awareness of this life-threatening pathology during cesarean delivery should be raised. Interdisciplinary assessment must be essentially established in this life-threatening condition. After the whole conventional management, uterine conservation may be acceptable where applicable. Further data is required to encourage this finding.

17.
ACS Nano ; 18(1): 199-209, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38109681

RESUMO

Tumor-derived extracellular vesicles (TDEs) have potential for therapeutic cancer vaccine applications since they innately possess tumor-associated antigens, mediate antigen presentation, and can incorporate immune adjuvants for enhanced vaccine efficacy. However, the original TDEs also contain immune-suppressive proteins. To address this, we proposed a simple yet powerful preconditioning method to improve the overall immunogenicity of the TDEs. This approach involved inducing endoplasmic reticulum (ER) stress on parental tumor cells via N-glycosylation inhibition with tunicamycin. The generated immunogenic TDEs (iTDEs) contained down-regulated immunosuppressive proteins and up-regulated immune adjuvants, effectively activating dendritic cells (DCs) in vitro. Furthermore, in vivo evidence from a tumor-bearing mouse model showed that iTDEs activated DCs, enabling cytotoxic T lymphocytes (CTLs) to target tumors, and eventually established a systemic antitumor immune response. Additionally, iTDEs significantly delayed tumor recurrence in a postsurgery model compared with control groups. These findings highlight the immense potential of our strategy for utilizing TDEs to develop effective cancer vaccines.


Assuntos
Vacinas Anticâncer , Vesículas Extracelulares , Neoplasias , Camundongos , Animais , Vacinas Anticâncer/uso terapêutico , Neoplasias/terapia , Linfócitos T Citotóxicos , Adjuvantes Imunológicos , Retículo Endoplasmático , Células Dendríticas
18.
Sci Rep ; 13(1): 18753, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37907691

RESUMO

This study aims to provide in vitro and in vivo data to support the utilization of antinuclear antibodies (ANAs) as novel tools for the diagnosis and treatment of prostate cancers. The hematological, biochemical, and histological toxicities of ANAs were assessed at the doses of 5 and 50 µg per mouse. Radiolabeling study was then conducted with ANA and 131I using the chloramine T method, and the biodistribution and treatment efficacy were subsequently investigated in a PC3 xenograft model. No changes in clinical behavior or signs of intoxication, necrosis, or malignancy were observed in ANA-treated mice. 131I-ANA was obtained in very high yield and radiochemical purity, at 94.97 ± 0.98% and 98.56 ± 0.29%, respectively. They achieved immunoreactivity fraction of 0.841 ± 0.17% with PC-3 cells. Levels of radiolabeled ANAs were 1.15-10.14 times higher in tumor tissues than in other examined organs at 24 h post-injection. The tumor growth inhibition rates were 28.33 ± 5.01% in PC3 xenografts mice treated with 131I-ANAs compared with controls and a nearly twofold improvement in median survival was observed. These results demonstrate that radioimmunotherapy of radiolabeled natural ANAs may be an effective treatment for prostate tumors.


Assuntos
Radioisótopos do Iodo , Neoplasias da Próstata , Masculino , Humanos , Animais , Camundongos , Radioisótopos do Iodo/uso terapêutico , Anticorpos Antinucleares , Xenoenxertos , Distribuição Tecidual , Neoplasias da Próstata/tratamento farmacológico , Linhagem Celular Tumoral
19.
Radiol Case Rep ; 18(12): 4533-4536, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37868012

RESUMO

A gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. The tumor originates from Cajal cells, which generated peristaltic motion. Primary gastrointestinal stromal tumor of the liver is rare and should be considered in imaging diagnosis. We report a case of an 82-year-old female patient who represented with upper abdominal pain and poor appetite. Magnetic resonance imaging detected a large left lobe cystic lesion (10 × 15 cm). The tumor was resected. The histopathological and immunohistochemical results were of a primary gastrointestinal stromal tumor in the liver with cystic changes. On imaging, it is difficult to differentiate from other cystic lesions.

20.
Nat Commun ; 14(1): 5503, 2023 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-37679347

RESUMO

Autophagosome formation, a crucial step in macroautophagy (autophagy), requires the covalent conjugation of LC3 proteins to the amino headgroup of phosphatidylethanolamine (PE) lipids. Atg3, an E2-like enzyme, catalyzes the transfer of LC3 from LC3-Atg3 to PEs in targeted membranes. Here we show that the catalytically important C-terminal regions of human Atg3 (hAtg3) are conformationally dynamic and directly interact with the membrane, in collaboration with its N-terminal membrane curvature-sensitive helix. The functional relevance of these interactions was confirmed by in vitro conjugation and in vivo cellular assays. Therefore, highly curved phagophoric rims not only serve as a geometric cue for hAtg3 recruitment, but also their interaction with hAtg3 promotes LC3-PE conjugation by targeting its catalytic center to the membrane surface and bringing substrates into proximity. Our studies advance the notion that autophagosome biogenesis is directly guided by the spatial interactions of Atg3 with highly curved phagophoric rims.


Assuntos
Autofagia , Fosfatidiletanolaminas , Humanos , Macroautofagia , Fenômenos Químicos , Membranas
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