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1.
Clin Transplant Res ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38725178

RESUMO

Organ transplantation from donors with immune thrombocytopenia (ITP), a condition involving the autoantibody-mediated destruction of platelets, is a topic of debate due to the potential for transplantation-mediated autoimmune thrombocytopenia (TMAT), a rare but potentially fatal complication. Previous reports have described transplants from deceased liver donors with ITP who had very low platelet counts and disease largely refractory to treatment. Here, we present the first case of living kidney transplantation from a donor with ITP who underwent preoperative treatment, with concurrent splenectomy performed to reduce the long-term risk of spontaneous hemorrhage. To ensure the safety of the procedure, we monitored perioperative rotational thromboelastometry parameters and platelet counts, leading to the normalization of the donor's platelet levels. The recipient experienced an uneventful recovery of renal function without perioperative bleeding or the development of TMAT. Our report suggests that kidney transplantation from a donor with well-managed ITP is safe, and such a condition should not be considered a contraindication for donation.

3.
J Bacteriol ; : e0004824, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38712944

RESUMO

Whole genome sequencing has revealed that the genome of Staphylococcus aureus possesses an uncharacterized 5-gene operon (SAOUHSC_00088-00092 in strain 8325 genome) that encodes factors with functions related to polysaccharide biosynthesis and export, indicating the existence of a new extracellular polysaccharide species. We designate this locus as ssc for staphylococcal surface carbohydrate. We found that the ssc genes were weakly expressed and highly repressed by the global regulator MgrA. To characterize Ssc, Ssc was heterologously expressed in Escherichia coli and extracted by heat treatment. Ssc was also conjugated to AcrA from Campylobacter jejuni in E. coli using protein glycan coupling technology (PGCT). Analysis of the heat-extracted Ssc and the purified Ssc-AcrA glycoconjugate by tandem mass spectrometry revealed that Ssc is likely a polymer consisting of N-acetylgalactosamine. We further demonstrated that the expression of the ssc genes in S. aureus affected phage adsorption and susceptibility, suggesting that Ssc is surface-exposed. IMPORTANCE: Surface polysaccharides play crucial roles in the biology and virulence of bacterial pathogens. Staphylococcus aureus produces four major types of polysaccharides that have been well-characterized. In this study, we identified a new surface polysaccharide containing N-acetylgalactosamine (GalNAc). This marks the first report of GalNAc-containing polysaccharide in S. aureus. Our discovery lays the groundwork for further investigations into the chemical structure, surface location, and role in pathogenesis of this new polysaccharide.

4.
Microsurgery ; 44(4): e31186, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38716649

RESUMO

INTRODUCTION: Free flap transfer for head and neck defects has gained worldwide acceptance. Because flap failure is a devastating outcome, studies have attempted to identify risk factors-including renal failure. We sought to determine whether end-stage renal disease (ESRD) patients undergoing dialysis are at increased risk of flap failure following microsurgical head and neck reconstruction. PATIENTS AND METHODS: The study's participants were patients who underwent free flap reconstruction in the head and neck region at Hualien Tzu Chi Hospital between January 2010 and December 2019. We used the National Health Insurance "Specific Diagnosis and Treatment Code" to identify patients undergoing dialysis; these patients comprised the dialysis group, whose members were matched to a non-dialysis group for age and gender. The dependent variables were flap survival rate, take-back rate, and flap failure risk between the dialysis and non-dialysis groups. RESULTS: We included 154 patients in the dialysis (n = 14) and non-dialysis (n = 140) groups. The groups were similar in terms of age and most comorbidities, except diabetes mellitus, hypertension, and coronary artery disease, which were more prevalent in the dialysis group. The dialysis and non-dialysis groups had similar flap survival rates (100% vs. 92.9%; p = .600). Twenty-three patients underwent take-back surgery, most in the non-dialysis group (14.3% vs. 15.0%; p = 1.000). Patients in the dialysis group were more likely to have prolonged intensive care unit stays; however, dialysis alone did not predict flap failure (OR: 0.83; p = .864). CONCLUSION: This study found no significant differences in free flap survival and take-back rates between patients with and without dialysis. Dialysis did not increase the risk of flap failure following microsurgical head and neck reconstruction in this study; however, prospective, randomized controlled trials are needed.


Assuntos
Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço , Falência Renal Crônica , Microcirurgia , Procedimentos de Cirurgia Plástica , Diálise Renal , Humanos , Masculino , Feminino , Falência Renal Crônica/terapia , Falência Renal Crônica/complicações , Pessoa de Meia-Idade , Retalhos de Tecido Biológico/transplante , Procedimentos de Cirurgia Plástica/métodos , Microcirurgia/métodos , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias de Cabeça e Pescoço/complicações , Idoso , Estudos Retrospectivos , Sobrevivência de Enxerto , Fatores de Risco , Adulto
5.
Environ Toxicol ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38717028

RESUMO

Salmonella infections are a serious global health concern, particularly in developing countries, and are further exacerbated by the emergence of antibiotic resistance. San-Huang-Xie-Xin-Tang (SHXXT), a traditional herbal medicine with potent anti-inflammatory properties, has recently gained attention as an alternative treatment. Our study emphasizes on the importance of precise timing in accordance with traditional Chinese medicine principles. A mouse infection model was established while different administration times of SHXXT were recorded for the body weight, clinical scores, bacterial counts in blood, and organs. Additionally, cytokine levels, fatty acids, and amino acids in the serum were also monitored. We found that administering SHXXT 1 day after Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) infection (T1 group) leads to positive outcomes. This includes restoration of body weight, improved clinical scores, and reduced bacterial counts in blood and vital organs. Interferon-gamma levels remained consistently high across all treatment groups 6 days post-infection. However, the T1 group showed exclusive suppression of serum levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß). The timing of administration significantly influenced serum fatty acid concentrations, countering Salmonella-induced disruptions, aligning with TNF-α and IL-1ß levels. SHXXT had also restored amino acid profiles disrupted by the infection, with notable effects when administered at the correct timing. Our research highlights SHXXT's potential in treating S. Typhimurium infection, emphasizing the importance of precise timing in line with traditional Chinese medicine principles for effective treatment at different disease stages.

6.
Curr Eye Res ; : 1-8, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38717215

RESUMO

PURPOSE: This study aimed to investigate the potential correlation between the single-nucleotide polymorphism (SNP) of maternally expressed gene 3 (MEG3) and the clinical manifestations of diabetic retinopathy (DR). METHODS: Five loci of MEG3 SNPs including rs4081134 (G/A), rs10144253 (T/C), rs7158663 (G/A), rs3087918 (T/G) and rs11160608 (A/C) were genotyped by TaqMan allelic discrimination in 457 non-DR patients and 280 DR individuals. RESULTS: The distribution frequency of MEG3 SNP rs7158663 GA (AOR: 0.683, 95% CI: 0.478-0.975, p = 0.036) and MEG3 SNP rs7158663 GA + AA (AOR: 0.686, 95% CI: 0.487-0.968, p = 0.032) were significantly lower in the DR group. And the MEG3 SNP rs7158663 GA + AA (AOR: 0.610, 95% CI: 0.377-0.985, p = 0.043) demonstrated a significantly lower distribution frequency in the male DR group. Besides, the DR patients with MEG3 SNP rs7158663 GA + AA genotype showed a significantly lower HbA1c level than the DR patients with MEG3 SNP rs7158663 GG genotype (7.29 ± 1.23 versus 7.74 ± 1.49, p = 0.013). Moreover, in the analysis using data from gene expression data series database, a higher MEG3 level was significantly correlated to a lower miR-182 level in the database (p = 0.0114). CONCLUSIONS: In this study, the distribution frequency of MEG3 SNP rs7158663 GA + AA genotype was lower in DR, while the DR would develop under lower HbA1c level in DM patients with this MEG3 SNP variant.

7.
Geriatr Nurs ; 57: 208-216, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38696878

RESUMO

Falls require comprehensive assessment in older adults due to their diverse risk factors. This study aimed to develop an effective fall risk prediction model for community-dwelling older adults by integrating principal component analysis (PCA) with machine learning. Data were collected for 45 fall-related variables from 1630 older adults in Taiwan, and models were developed using PCA and logistic regression. The optimal model, PCA with stepwise logistic regression, had an area under the receiver operating characteristic curve of 0.78, sensitivity of 74 %, specificity of 70 %, and accuracy of 71 %. While dimensionality reduction via PCA is not essential, it aids practicality. Our framework combines PCA and logistic regression, providing a reliable method for fall risk prediction to support consistent screening and targeted health promotion. The key innovation is using PCA prior to logistic regression, overcoming conventional limitations. This offers an effective community-based fall screening tool for older adults.

8.
J Clin Med ; 13(9)2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38731099

RESUMO

Background/Objectives: Metabolic syndrome (MS) is a constellation of several cardiometabolic risk factors. We investigated sex disparity in the associations between MS and cognitive impairment using cross-sectional data from Taiwan Biobank. Methods: We determined the associations of MS and its five components with cognitive impairment (mini-mental state examination, MMSE < 24) and the five domains of MMSE using logistic regression analyses. Results: A total of 7399 men and 11,546 women were included, and MS was significantly associated with cognitive impairment only in women (adjusted OR 1.48, 95% CI 1.29-1.71, p = 0.001) (p for interaction 0.005). In women, the association with MS was significant in orientation (adjusted OR 1.21, 95% CI 1.07-1.37, p = 0.003), memory (adjusted OR 1.12, 95% CI 1.01-1.25, p = 0.034) and design copying (adjusted OR 1.41, 95% CI 1.23-1.62, p = 0.001) (p value for interaction 0.039, 0.023, and 0.093, respectively). Among the components of MS, a large waist circumference (adjusted OR 1.25, 95% CI 1.08-1.46, p = 0.003), high fasting glucose (adjusted OR 1.16, 95% CI 1.00-1.34, p = 0.046), and low HDL cholesterol (adjusted OR 1.16, 95% CI 1.00-1.34, p = 0.049) were significantly associated with cognitive impairment in women. Conclusions: Our findings suggest that sex has a significant influence on the association between MS and cognitive dysfunction, especially in orientation and memory.

9.
Diagnostics (Basel) ; 14(8)2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38667502

RESUMO

Myxofibrosarcoma is a type of soft tissue sarcoma, predominantly characterized by a high propensity for local recurrence, albeit demonstrating a relatively diminished risk for distant metastasis. Its prevalence is notably higher in elderly patients. Here, we present a case of a 73-year-old woman diagnosed with Myxofibrosarcoma. She was subjected to a whole-body bone scan using 99mTc-methylene diphosphonate (MDP) to survey potential bony metastasis. It revealed marked MDP accumulation with peripheral soft tissue uptake in the right lateral chest region of this patient. This imaging phenotype could potentially be attributed to the augmented vascularity within the tumor, a finding that was prominently displayed in this particular case.

10.
Eur J Med Res ; 29(1): 245, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649928

RESUMO

BACKGROUND: To determine the effect of colchicine on cancer risk in patients with the immune-mediated inflammatory diseases (IMIDs)-related to colchicine use. METHODS: This is a time-dependent propensity-matched general population study based on the National Health Insurance Research Database (NHIRD) of Taiwan. We identified the IMIDs patients (n = 111,644) newly diagnosed between 2000 and 2012 based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)-274,712, 135, 136.1, 279.49, 518.3, 287.0, 696.0, 696.1, 696.8, 420, 429.4, 710.0, 710.1, 710.3, 710.4, 714.0, 720, 55.0, 55.1, 55.9, 556. INCLUSION CRITERIA: aged ≧ 20 years, if a patient had at least these disease diagnosis requirements within 1 year of follow-up, and, these patients had at least two outpatient visits or an inpatient visit. After propensity-matched according to age, sex, comorbidities, medications and index date, the IMIDs patients enter into colchicine users (N = 16,026) and colchicine nonusers (N = 16,026). Furthermore, time-dependent Cox models were used to analyze cancer risk in propensity-matched colchicine users compared with the nonusers. The cumulative cancer incidence was analyzed using Cox proportional regression analysis. We calculated adjusted hazard ratios (aHRs) and their 95% confidence intervals (95% CIs) for cancer after adjusting for sex, age, comorbidities, and use of medicine including acetylcysteine, medication for smoking cessation such as nicotine replacement medicines (the nicotine patch) and pill medicines (varenicline), anti-inflammatory drugs and immunosuppressant drugs. RESULTS: Comparing the colchicine nonusers, all cancer risk were mildly attenuated, the (aHR (95% CI)) of all cancer is (0.84 (0.55, 0.99)). Meanwhile, the colchicine users were associated with the lower incidence of the colorectal cancer, the (aHRs (95% CI)) is (0.22 (0.19, 0.89)). Those aged < 65 years and male/female having the colchicine users were associated with lower risk the colorectal cancer also. Moreover, the colchicine > 20 days use with the lower aHR for colorectal cancer. CONCLUSION: Colchicine was associated with the lower aHR of the all cancer and colorectal cancer formation in patients with the IMIDs.


Assuntos
Colchicina , Bases de Dados Factuais , Programas Nacionais de Saúde , Neoplasias , Humanos , Colchicina/uso terapêutico , Feminino , Masculino , Taiwan/epidemiologia , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Idoso , Programas Nacionais de Saúde/estatística & dados numéricos , Adulto , Fatores de Risco , Inflamação/tratamento farmacológico , Incidência
11.
Front Pharmacol ; 15: 1326415, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38606179

RESUMO

Yi Mai Jian herbal formula (YMJ) is formulated with Eucommiae Folium, Astragali Radix, Ligustri Lucidi Fructus, and Elaeagnus Fructus to improve bone function in traditional Chinese medicine. The anti-osteoporotic effects of YMJ in bone metabolism were evaluated in ovariectomized (OVX) rats. The skeletal structure of the femur and vertebrae was analyzed after treating OVX rats with YMJ for 114 days. The results showed that YMJ significantly increased the bone mineral density (BMD) and trabecular number (Tb. N) of the femur and 5th lumbar vertebrae and reduced trabecular separation (Tb. Sp). Moreover, trabecular bone volume/total tissue volume (BV/TV), bone stiffness, and maximum femur load were significantly increased. The serum concentrations of NTX1 and PYD were significantly decreased. According to these results, YMJ could ameliorate osteoporosis in ovariectomized rats. Eucommiae Folium and Elaeagnus Fructus inhibited osteoclast differentiation, Ligustri Lucidi Fructus inhibited calcium reabsorption, Astragali Radix stimulated osteoblast proliferation, and Astragali Radix and Eucommiae Folium stimulated mineralization. Therefore, the combination of the four herbs into one formula, YMJ, could alleviate bone remodeling caused by low estrogen levels. We suggest that YMJ could be a healthy food candidate for preventing post-menopausal osteoporosis.

12.
Cancer Med ; 13(7): e7132, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38606892

RESUMO

BACKGROUND: Fertility-sparing surgery (FSS) is an alternative choice of young patients who have not completed their family planning and still have fertility needs. The aims of this study were to compare the outcomes of early-stage epithelial ovarian cancer (EOC) patients undergoing FSS and radical comprehensive staging surgery (RCS), and the suitability of FSS. METHODS: A total of 1297 patients aged between 20 and 44 years with newly diagnosed early-stage EOC were recruited from the Taiwan Cancer Registry database between 2009 and 2017. Site-specific surgery codes were used to distinguish patients in FSS group or RCS group. Cancer-specific survival (CSS) was evaluated using Kaplan-Meier method with log-rank test and Cox regression model. RESULTS: There were 401 and 896 patients in FSS and RCS group. Patients in FSS group were with younger age and mostly had Stage I disease. In contrast, patients in RCS group were older. There were more Stage II, high-grade (Grade 3) disease, and adjuvant chemotherapy in RCS group. Stage and tumor grade were two independent factors correlating with CSS and the type of surgery showed no effect on CSS (HR: 1.09, 95% CI: 0.66-1.77, p = 0.73) in multivariable analysis. In multivariable analysis, the clear cell carcinoma group who underwent FSS demonstrated better CSS compared to those in the RCS group (HR: 0.28, 95% CI: 0.06-0.82, p = 0.04). A total of 17 women who underwent FSS developed second malignancies of the uterine corpus or contralateral ovary. CONCLUSION: FSS can be a safe alternative procedure in selected young patients of Stage I EOC who have fertility desire. Endometrial biopsy before or during FSS and regular surveillance to detect recurrence are mandatory for ovarian cancer patients undergoing FSS.


Assuntos
Preservação da Fertilidade , Neoplasias Ovarianas , Humanos , Feminino , Adulto Jovem , Adulto , Estudos Retrospectivos , Carcinoma Epitelial do Ovário/cirurgia , Carcinoma Epitelial do Ovário/patologia , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/tratamento farmacológico , Estadiamento de Neoplasias
13.
Cells ; 13(7)2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38607055

RESUMO

The management of chronic myelogenous leukemia (CML) has seen significant progress with the introduction of tyrosine kinase inhibitors (TKIs), particularly Imatinib. However, a notable proportion of CML patients develop resistance to Imatinib, often due to the persistence of leukemia stem cells and resistance mechanisms independent of BCR::ABL1 This study investigates the roles of IL6R, IL7R, and MYC in Imatinib resistance by employing CRISPR/Cas9 for gene editing and the Non-Invasive Apoptosis Detection Sensor version 2 (NIADS v2) for apoptosis assessment. The results indicate that Imatinib-resistant K562 cells (K562-IR) predominantly express IL6R, IL7R, and MYC, with IL6R and MYC playing crucial roles in cell survival and sensitivity to Imatinib. Conversely, IL7R does not significantly impact cytotoxicity, either alone or in combination with Imatinib. Further genetic editing experiments confirm the protective functions of IL6R and MYC in K562-IR cells, suggesting their potential as therapeutic targets for overcoming Imatinib resistance in CML. This study contributes to understanding the mechanisms of Imatinib resistance in CML, proposing IL6R and MYC as pivotal targets for therapeutic strategies. Moreover, the utilization of NIADS v2 enhances our capability to analyze apoptosis and drug responses, contributing to a deeper understanding of CML pathogenesis and treatment options.


Assuntos
Biomarcadores , Leucemia Mielogênica Crônica BCR-ABL Positiva , Proteínas Proto-Oncogênicas c-myc , Receptores de Interleucina-6 , Humanos , Apoptose , Resistencia a Medicamentos Antineoplásicos , Mesilato de Imatinib/farmacologia , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico
14.
Klin Monbl Augenheilkd ; 241(4): 540-544, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38653312

RESUMO

BACKGROUND: Performance and symptoms in completing a visual search task on a PC monitor and using a head-mounted display (HMD) were compared for different viewing conditions and between users of different ages. PATIENTS AND METHODS: Twenty-three young (M = 30 y, SD = 7 y) and 23 older (M = 52 y, SD = 5 y) participants performed a visual search task presented on a PC monitor. The task was repeated using an HMD for a near and a far virtual viewing distance. Reaction times (RT), detection sensitivity (d'), and symptoms were recorded for the three different viewing conditions. RESULTS: RT and d' were not affected by the viewing condition (p > 0.05). In contrast, symptoms significantly depended on the viewing condition but were, in part, not significantly affected by age. It is interesting to note that although not significant, young participants reported more ocular symptoms than older participants in the near vision task carried out using the HMD. DISCUSSION: HMD increases visual symptoms. However, HMD could be, in part, a remedy to problems when using visual aids for near work, in particular for presbyopes.


Assuntos
Acomodação Ocular , Presbiopia , Realidade Virtual , Humanos , Presbiopia/fisiopatologia , Presbiopia/terapia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Acomodação Ocular/fisiologia , Convergência Ocular/fisiologia , Adulto Jovem , Tempo de Reação/fisiologia
15.
Environ Toxicol ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654487

RESUMO

Proliferative vitreoretinopathy (PVR) is a visual-threatening disease, which cause from the migration of retinal pigment epithelium (RPE). Tricetin, a family of flavonoids, can inhibit the metastasis of several cancers. Herein, we aim to evaluate the possible effect of tricetin on inhibiting ARPE-19 cells migration. The Boyden chamber assay, wound healing assay, RNA sequencing, and Western blot analysis were applied in our experiment. The results revealed that tricetin inhibited the cell migration abilities of ARPE-19 cells. Moreover, using RNA sequencing technology, we revealed that tricetin repressed bone morphogenetic protein-6 (BMP-6) gene expressions in ARPE-19 cells. Overexpression of BMP-6 resulted in significant restoration of cell migration capabilities of tricetin-treated ARPE-19 cells. Furthermore, tricetin suppressed the phosphorylation of the p38 signaling pathway. Moreover, blocking the p38 pathway also inhibits BMP-6 expression and migration in the ARPE-19 cells. In conclusion, this study revealed that tricetin inhibits the ARPE-19 cell migration mainly via the suppression of BMP-6 expression and p38 signaling pathway.

16.
Sci Rep ; 14(1): 8732, 2024 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627567

RESUMO

We sought to evaluate the topographic risk factors for early myopic regression after small-incision lenticule extraction (SMILE). A retrospective case‒control study was conducted, and individuals who underwent SMILE surgery were enrolled. Among them, 406 and 14 eyes were categorized into the nonregression and regression groups, respectively. The preoperative and postoperative parameters in the two groups were collected, including spherical refraction (SE), axial length (AXL) and topographic data. A generalized linear model was adopted to analyze the difference in each parameter between the two groups. After 6 months, UCVA decreased in the regression group, and SE increased in the regression group (both P < 0.05). The increase in the CCT at the thinnest point (P = 0.044), flat corneal curvature (P = 0.012) and TCRP (P = 0.001) were significantly greater in the regression group. Regarding the risk factors for myopic regression, preoperative SE, preoperative sphere power, preoperative AXL, preoperative flat corneal curvature, preoperative SA, early postoperative SE, early postoperative sphere power, early postoperative AXL and early postoperative CCT difference were significantly greater in the regression group (all P < 0.05). The SE, sphere power, AXL, preoperative flat corneal curvature, preoperative SA, and postoperative CCT difference correlate with early myopic regression after SMILE.


Assuntos
Cirurgia da Córnea a Laser , Miopia , Ferida Cirúrgica , Humanos , Córnea/cirurgia , Substância Própria/cirurgia , Acuidade Visual , Estudos Retrospectivos , Estudos de Casos e Controles , Cirurgia da Córnea a Laser/efeitos adversos , Lasers de Excimer/uso terapêutico , Refração Ocular , Miopia/cirurgia , Ferida Cirúrgica/cirurgia
17.
Cytotherapy ; 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38625070

RESUMO

BACKGROUND: Adipose-derived stem cells (ASCs) are recognized for their potential immunomodulatory properties. In the immune system, tolerogenic dendritic cells (DCs), characterized by an immature phenotype, play a crucial role in inducing regulatory T cells (Tregs) and promoting immune tolerance. Notch1 signaling has been identified as a key regulator in the development and function of DCs. However, the precise involvement of Notch1 pathway in ASC-mediated modulation of tolerogenic DCs and its impact on immune modulation remain to be fully elucidated. This study aims to investigate the interplay between ASCs and DCs, focusing the role of Notch1 signaling and downstream pathways in ASC-modulated tolerogenic DCs. METHODS: Rat bone marrow-derived myeloid DCs were directly co-cultured with ASCs to generate ASC-treated DCs (ASC-DCs). Notch signaling was inhibited using DAPT, while NFκB pathways were inhibited by NEMO binding domain peptide and si-NIK. Flow cytometry assessed DC phenotypes. Real-time quantitative PCR, Western blotting and immunofluorescence determined the expression of Notch1, Jagged1 and the p52/RelB complex in ASC- DCs. RESULTS: Notch1 and Jagged1 were highly expressed on both DCs and ASCs. ASC-DCs displayed significantly reduced levels of CD80, CD86 and MHC II compared to mature DCs. Inhibiting the Notch pathway with DAPT reversed the dedifferentiation effects. The percentage of induced CD25+/FOXP3+/CD4+ Tregs decreased when ASC-DCs were treated with DAPT (inhibition of the Notch pathway) and si-NIK (inhibition of the non-canonical NFκB pathway). CONCLUSIONS: ASCs induce DC tolerogenicity by inhibiting maturation and promoting downstream Treg generation, involving the Notch and NFκB pathways. ASC-induced tolerogenic DCs can be a potential immunomodulatory tool for clinical application.

18.
Life (Basel) ; 14(4)2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38672800

RESUMO

We aim to investigate the potential correlation between the presence of ovarian cancer and the development of dry eye disease (DED) via the usage of the Longitudinal Health Insurance Database (LHID) of Taiwan. A retrospective cohort study was executed, and patients with ovarian cancer were selected according to the diagnostic and procedure codes. One ovarian cancer patient was matched to four non-ovarian cancer participants which served as control group, and a total of 4992 and 19,968 patients constructed the ovarian cancer and control groups, respectively. The primary outcome in the current study is the development of DED according to the diagnostic and procedure codes. Cox proportional hazard regression was utilized to produce the adjusted hazard ratio (aHR) and related 95% confidence interval (CI) of DED between the two groups. There were 542 and 2502 DED events observed in the ovarian cancer group and the control group, respectively. The ovarian cancer group illustrated a significantly higher incidence of DED development than the control group after the adjustment of several confounders (aHR: 1.10, 95% CI: 1.01-1.21, p = 0.040). In the subgroup analysis stratified by age, ovarian cancer patients aged older than 60 years showed a higher incidence of DED compared to the non-ovarian cancer population (aHR: 1.19, 95% CI: 1.08-1.28, p = 0.011). In addition, ovarian cancer patients with a disease duration longer than five years also showed higher incidence of DED formation than the non-ovarian cancer population (aHR: 1.13, 95% CI: 1.04-1.22, p = 0.027). In conclusion, the presence of ovarian cancer is associated with higher incidence of subsequent DED, especially in those older than 60 years and with a disease interval of more than five years.

19.
Nat Med ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684860

RESUMO

The early identification of vulnerable patients has the potential to improve outcomes but poses a substantial challenge in clinical practice. This study evaluated the ability of an artificial intelligence (AI)-enabled electrocardiogram (ECG) to identify hospitalized patients with a high risk of mortality in a multisite randomized controlled trial involving 39 physicians and 15,965 patients. The AI-ECG alert intervention included an AI report and warning messages delivered to the physicians, flagging patients predicted to be at high risk of mortality. The trial met its primary outcome, finding that implementation of the AI-ECG alert was associated with a significant reduction in all-cause mortality within 90 days: 3.6% patients in the intervention group died within 90 days, compared to 4.3% in the control group (4.3%) (hazard ratio (HR) = 0.83, 95% confidence interval (CI) = 0.70-0.99). A prespecified analysis showed that reduction in all-cause mortality associated with the AI-ECG alert was observed primarily in patients with high-risk ECGs (HR = 0.69, 95% CI = 0.53-0.90). In analyses of secondary outcomes, patients in the intervention group with high-risk ECGs received increased levels of intensive care compared to the control group; for the high-risk ECG group of patients, implementation of the AI-ECG alert was associated with a significant reduction in the risk of cardiac death (0.2% in the intervention arm versus 2.4% in the control arm, HR = 0.07, 95% CI = 0.01-0.56). While the precise means by which implementation of the AI-ECG alert led to decreased mortality are to be fully elucidated, these results indicate that such implementation assists in the detection of high-risk patients, prompting timely clinical care and reducing mortality. ClinicalTrials.gov registration: NCT05118035 .

20.
Molecules ; 29(8)2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38675568

RESUMO

Reactions of Co(OAc)2·4H2O, N'N'-bis(3-pyridylmethyl)oxalamide (L) and 4,4'-sulfonyldibenzoic acid (H2SDA) afforded four coordination polymers with the same mixed ligands, {[Co(L)(SDA)(H2O)2]·H2O·CH3OH}n, 1, {[Co(L)0.5(SDA)]·2H2O·0.5L}n, 2, {[Co(L)1.5(SDA)(H2O)]·H2O}n, 3, and {[Co2(L)1.5(SDA)2(H2O)2]·4H2O}n, 4, which have been structurally characterized using single-crystal X-ray crystallography. Complexes 1-4 are 2D layers, revealing topologies of sql, 2,6L1, (4,4)Ia, and 6L12, respectively, and demonstrating that the metal-to-ligand ratio, solvent system, and reaction temperature are important in determining the structural diversity. The immersion of these complexes into various solvents shows that the structural types govern the chemical stabilities of 1-4. Reversible structural transformation is shown for complexes 1 and 2 upon solvent removal and adsorption, while those of 3 and 4 are irreversible.

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