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1.
J Surg Orthop Adv ; 33(2): 112-116, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38995069

RESUMEN

We investigated the effect of robotic assistance in a postoperative change in hip offset and the incidence of trochanteric bursitis among total hip arthroplasty (THA) patients. As part of a retrospective study of a consecutive series of patients over a 3-year period, 211 patients (102 traditional; 109 robotic) between 2013 and 2016 who underwent posterior-lateral THA were reviewed. Hip offset was measured on preoperative and postoperative anterior-posterior (AP) pelvis radiographs. The absolute change in total hip offset was higher in patients undergoing non-robotic THA than in patients undergoing robotic THA (5.98 ± 4.47 mm vs 4.33 ± 3.98 mm; p = 0.008). The rate of symptomatic trochanteric bursitis (p = 0.02) and cortisone injection was higher in non-robotic THA patients than in robotic THA patients (p = 0.002). Robotic arm-assisted THA is associated with a decreased postoperative change in hip offset, incidence of symptomatic trochanteric bursitis, and bursal steroid injections. (Journal of Surgical Orthopaedic Advances 32(4):112-116, 2023).


Asunto(s)
Artroplastia de Reemplazo de Cadera , Bursitis , Complicaciones Posoperatorias , Procedimientos Quirúrgicos Robotizados , Humanos , Artroplastia de Reemplazo de Cadera/métodos , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Procedimientos Quirúrgicos Robotizados/métodos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Articulación de la Cadera/diagnóstico por imagen
2.
Adv Healthc Mater ; : e2400170, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38989721

RESUMEN

Chronic wounds adversely affect the quality of life. Although electrical stimulation has been utilized to treat chronic wounds, there are still limitations to practicing it due to the complicated power system. Herein, an electrostimulating membrane incorporated with electrospun nanofiber (M-sheet) to treat diabetic wounds is developed. Through the screen printing method, the various alternate patterns of both Zn and AgCl on a polyurethane substrate, generating redox-mediated electrical fields are introduced. The antibacterial ability of the patterned membrane against both E. coli and S. aureus is confirmed. Furthermore, the poly(vinyl alcohol) (PVA)/gelatin electrospun fiber is incorporated into the patterned membrane to enhance biocompatibility and maintain the wet condition in the wound environment. The M-sheet can improve cell proliferation and migration in vitro and has an immune regulatory effect by inducing the polarization of macrophage to the M2 phenotype. Finally, when applied to a diabetic skin wound model, the M-sheet displays an accelerated wound healing rate and enhances re-epithelialization, collagen synthesis, and angiogenesis. It suggests that the M-sheet is a simple and portable system for the spontaneous generation of electrical stimulation and has great potential to be used in the practical wound and other tissue engineering applications.

3.
Epidemiol Health ; : e2024066, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39054626

RESUMEN

Objectives: This study investigated the associations between several obesity-related anthropometric indices and mortality in middle-aged and elderly populations to compare the indices' predictive ability with that of the body mass index (BMI). Methods: We analyzed data on 12 indices calculated from 19,805 community-based cohort participants (average age, 63.27 years; median follow-up, 13.49 years). Each index was calculated using directly measured values of height, weight, waist circumference (WC), and hip circumference (HC). We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for each index using Cox regression and evaluated mortality prediction with the Harrell c-index. Results: Adding anthropometric indices to the basic mortality model (c-index 0.7723; 95% CI, 0.7647-0.7799) significantly increased the predictive power of BMI (c-index 0.7735; 95% CI, 0.7659-0.7811), a body shape index (ABSI, c-index 0.7735; 95% CI, 0.7659-0.7810), weight-adjusted waist index (WWI, c-index 0.7731; 95% CI, 0.7656-0.7807), and waist to hip index (WHI, c-index 0.7733; 95% CI, 0.7657-0.7809). The differences between the BMI model and the other 3 models were not statistically significant. Conclusion: In predicting all-cause mortality, the ABSI, WWI, and WHI models based on WC or HC had stronger predictive power than conventional risk factors but were not significantly different from the BMI model.

4.
J Hepatocell Carcinoma ; 11: 1235-1249, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38974017

RESUMEN

Introduction: We aimed to evaluate the generalizability of retrospective single-center cohort studies on prognosis of hepatocellular carcinoma (HCC) by comparing overall survival (OS) after various treatments between a nationwide multicenter cohort and a single-center cohort of HCC patients. Methods: Patients newly diagnosed with HCC between January 2008 and December 2018 were analyzed using data from the Korean Primary Liver Cancer Registry (multicenter cohort, n=16,443), and the Asan Medical Center HCC registry (single-center cohort, n=15,655). The primary outcome, OS after initial treatment, was compared between the two cohorts for both the entire population and for subcohorts with Child-Pugh A liver function (n=2797 and n=5151, respectively) treated according to the Barcelona-Clinic-Liver-Cancer (BCLC) strategy, using Log rank test and Cox proportional hazard models. Results: Patients of BCLC stages 0 and A (59.3% vs 35.2%) and patients who received curative treatment (42.1% vs 32.1%) were more frequently observed in the single-center cohort (Ps<0.001). Multivariable analysis revealed significant differences between the two cohorts in OS according to type of treatment: the multicenter cohort was associated with higher risk of mortality among patients who received curative (adjusted hazard ratio [95% confidence interval], 1.48 [1.39-1.59]) and non-curative (1.22 [1.17-1.27]) treatments, whereas the risk was lower in patients treated with systemic therapy (0.83 [0.74-0.92]) and best supportive care (0.85 [0.79-0.91]). Subcohort analysis also demonstrated significantly different OS between the two cohorts, with a higher risk of mortality in multicenter cohort patients who received chemoembolization (1.72 [1.48-2.00]) and ablation (1.44 [1.08-1.92]). Conclusion: Comparisons of single-center and multicenter cohorts of HCC patients revealed significant differences in OS according to treatment modality after adjustment for prognostic variables. Therefore, the results of retrospective single-center cohort studies of HCC treatments may not be generalizable to real-world practice.

5.
J Orthop Trauma ; 38(8): 426-430, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39007658

RESUMEN

OBJECTIVES: To determine the effectiveness of an updated protocol that increased the transfusion threshold to perform preperitoneal pelvic packing in patients with pelvic ring injuries and hemodynamic instability (HDI). DESIGN: Retrospective review. SETTING: Urban level 1 trauma center. PATIENTS SELECTION CRITERIA: Severely injured (injury severity score > 15) patients with pelvic ring injuries treated before and after increasing the threshold to perform preperitoneal pelvic packing from 2 to 4 units of red blood cells (RBCs). HDI was defined as a systolic blood pressure <90 mm Hg. OUTCOME MEASURES AND COMPARISONS: Mortality from hemorrhage, anterior pelvic space infections, and venous thromboembolisms before and after increasing preperitoneal pelvic packing threshold. RESULTS: One hundred sixty-six patients were included: 93 treated under the historical protocol and 73 treated under the updated protocol. HDI was present in 46.2% (n = 43) of the historical protocol group and 49.3% (n = 36) of the updated protocol group (P = 0.69). The median age of patients with HDI was 35.0 years (interquartile range 26.0-52.0), 74.7% (n = 59) were men, and the median injury severity score was 41.0 (interquartile range 29.0-50.0). Patients with HDI in the updated protocol group had a lower heart rate on presentation (105.0 vs. 120.0; P = 0.004), required less units of RBCs over the first 24 hours (6.0 vs. 8.0, P = 0.03), and did not differ in age, injury severity score, systolic blood pressure on arrival, base deficit or lactate on arrival, resuscitative endovascular balloon occlusion of the aorta, resuscitative thoracotomy, angioembolization, or anterior pelvis open reduction internal fixation (P > 0.05). The number of PPPs performed decreased under the new protocol (8.3% vs. 65.1%, P < 0.0001), and there were fewer anterior pelvic infections (0.0% vs. 13.9%, P = 0.02), fewer VTEs (8.3% vs. 30.2%; P = 0.02), and no difference in deaths from acute hemorrhagic shock (5.6% vs. 7.0%, P = 1.00). CONCLUSIONS: Increasing the transfusion threshold from 2 to 4 units of red blood cells to perform pelvic packing in severely injured patients with pelvic ring injuries decreased anterior pelvic space infections and venous thromboembolisms without affecting deaths from acute hemorrhage. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Asunto(s)
Huesos Pélvicos , Humanos , Masculino , Femenino , Adulto , Estudios Retrospectivos , Persona de Mediana Edad , Huesos Pélvicos/lesiones , Resultado del Tratamiento , Hemorragia/mortalidad , Hemorragia/prevención & control , Transfusión Sanguínea/estadística & datos numéricos , Fracturas Óseas/cirugía , Técnicas Hemostáticas , Puntaje de Gravedad del Traumatismo
6.
iScience ; 27(7): 110137, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39006481

RESUMEN

Pituitary adenoma-induced excess endocrine growth hormone (GH) secretion can lead to breast cancer development and metastasis. Herein, we used an acromegaly mouse model to investigate the role of excess endocrine GH on triple-negative breast cancer (TNBC) growth and metastasis. Additionally, we aimed to elucidate the molecular mechanism of transcription factor 20 (TCF20)/nuclear factor erythroid 2-related factor 2 (NRF2) signaling-mediated aggressiveness and metastasis of TNBC. Excess endocrine GH induced TCF20 activates the transcription of NRF2 and NRF2-target genes to facilitate TNBC metastasis. Inhibition of GH receptor (GHR) and TCF20 activity using the GHR antagonist or small-interfering RNA-induced gene knockdown resulted in reduced tumor volume and metastasis, suggesting that excess endocrine GH stimulates TCF20/NRF2 pathways in TNBC and promotes metastasis to the lung. GHR inhibitors present an effective therapeutic strategy to prevent TNBC cell growth and metastasis. Our findings revealed functional and mechanistic roles of the GH-TCF20-NRF2 signaling axis in TBNC progression.

7.
World J Microbiol Biotechnol ; 40(9): 261, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38972914

RESUMEN

The fecal microbiota of two healthy adults was cultivated in a medium containing commercial fructooligosaccharides [FOS; 1-kestose (GF2), nystose (GF3), and 1F-fructofuranosylnystose (GF4)]. Initially, the proportions of lactobacilli in the two feces samples were only 0.42% and 0.17%; however, they significantly increased to 7.2% and 4.8%, respectively, after cultivation on FOS. Most FOS-utilizing isolates could utilize only GF2; however, Lacticaseibacillus paracasei strain Lp02 could fully consume GF3 and GF4 too. The FOS operon (fosRABCDXE) was present in Lc. paracasei Lp02 and another Lc. paracasei strain, KCTC 3510T, but fosE was only partially present in the non-FOS-degrading strain KCTC 3510T. In addition, the top six upregulated genes in the presence of FOS were fosABCDXE, particularly fosE. FosE is a ß-fructosidase that hydrolyzes both sucrose and all three FOS. Finally, a genome-based analysis suggested that fosE is mainly observed in Lc. paracasei, and only 13.5% (61/452) of their reported genomes were confirmed to include it. In conclusion, FosE allows the utilization of FOS, including GF3 and GF4 as well as GF2, by some Lc. paracasei strains, suggesting that this species plays a pivotal role in FOS utilization in the human gut.


Asunto(s)
Heces , Microbioma Gastrointestinal , Lacticaseibacillus paracasei , Oligosacáridos , beta-Fructofuranosidasa , Humanos , Oligosacáridos/metabolismo , Heces/microbiología , Lacticaseibacillus paracasei/metabolismo , Lacticaseibacillus paracasei/genética , beta-Fructofuranosidasa/metabolismo , beta-Fructofuranosidasa/genética , Adulto , Operón , Trisacáridos/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo
8.
Nutrients ; 16(12)2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38931240

RESUMEN

Osteoarthritis (OA) is a chronic degenerative joint disease that causes chronic pain, swelling, stiffness, disability, and significantly reduces the quality of life. Typically, OA is treated using painkillers and non-steroidal anti-inflammatory drugs (NSAIDs). While current pharmacologic treatments are common, their potential side effects have prompted exploration into functional dietary supplements. Recently, eggshell membrane (ESM) has emerged as a potential functional ingredient for joint and connective tissue disorders due to its clinical efficacy in relieving joint pain and stiffness. Despite promising clinical evidence, the effects of ESM on OA progression and its mechanism of action remain poorly understood. This study evaluated the efficacy of Ovomet®, a powdered natural ESM, against joint pain and disease progression in a monosodium iodoacetate (MIA)-induced rodent model of OA in mice and rats. The results demonstrate that ESM significantly alleviates joint pain and attenuates articular cartilage destruction in both mice and rats that received oral supplementation for 5 days prior to OA induction and for 28 days thereafter. Interestingly, ESM significantly inhibited mRNA expression levels of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), as well as inflammatory mediators, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase in the knee joint cartilage at the early stage of OA, within 7 days after OA induction. However, this effect was not observed in the late stage at 28 days after OA induction. ESM further attenuates the induction of protein expression for cartilage-degrading enzymes like matrix metalloproteinase (MMPs) 3 and 13, and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), in the late-stage. In addition, MIA-induced reduction of the protein expression levels of cartilage components, cartilage oligomeric matrix protein (COMP), aggrecan (ACAN) and collagen type II α-1 chain (COL2α1), and cartilage extracellular matrix (ECM) synthesis promoting transcriptional factor SRY-Box 9 (SOX-9) were increased via ESM treatment in the cartilage tissue. Our findings suggest that Ovomet®, a natural ESM powder, is a promising dietary functional ingredient that can alleviate pain, inflammatory response, and cartilage degradation associated with the progression of OA.


Asunto(s)
Cartílago Articular , Cáscara de Huevo , Osteoartritis , Animales , Cartílago Articular/efectos de los fármacos , Cartílago Articular/metabolismo , Cartílago Articular/patología , Osteoartritis/tratamiento farmacológico , Osteoartritis/inducido químicamente , Masculino , Ratones , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Ratas , Inflamación/tratamiento farmacológico , Suplementos Dietéticos , Citocinas/metabolismo , Modelos Animales de Enfermedad , Ratas Sprague-Dawley , Artralgia/tratamiento farmacológico , Artralgia/inducido químicamente , Factores de Tiempo , Ácido Yodoacético , Antiinflamatorios/farmacología
10.
Artículo en Inglés | MEDLINE | ID: mdl-38887918

RESUMEN

BACKGROUND: Being overweight is a key modifiable risk factor for cardiovascular disease. However, the impact of longitudinal changes in body mass index (BMI) on the risk of out-of-hospital cardiac arrests (OHCA) remains unclear, especially among overweight populations. METHODS: This nested case-control study utilized data from the Korean National Health Information Database between 2009 and 2018. A total of 23 453 OHCA patients, who underwent national health check-ups within 1 and 2-4 years before OHCA occurrence, and 31 686 controls, who underwent similar national health check-ups, were included. The study population was matched for sex, age and survival status. Conditional logistic regression was employed to analyse the odds ratios (ORs) and 95% confidence intervals (CIs) of each BMI per cent change in assessing the risk of OHCA occurrence within 1 year. RESULTS: A reverse J-shaped association between BMI per cent change and OHCA risk was observed, even among overweight populations. Among the overweight populations, weight loss significantly increased OHCA risk, with ORs (95% CI) of 4.10 (3.23-5.20) for severe weight loss (BMI decrease > 15%), 2.72 (2.33-3.17) for moderate weight loss (BMI decrease 10-15%) and 1.46 (1.35-1.59) for mild weight loss (BMI decrease 5-10%). Conversely, mild weight gain (BMI increase 5-10%) did not significantly increase OHCA risk. The impact of weight changes on the occurrence of OHCA differed by sex, being more prominent in males. CONCLUSIONS: Significant weight changes within a 4-year period increase the risk of OHCA with a reverse J-shaped association, even among overweight and obese individuals. Maintaining a stable weight could be a reliable public health strategy irrespective of the weight status, particularly for males.

11.
J Cardiovasc Imaging ; 32(1): 6, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38907294

RESUMEN

BACKGROUND: Patients with end-stage renal disease (ESRD) who are on hemodialysis (HD) have reduced vascular compliance and are likely to develop heart failure (HF). In this study, we estimated the prevalence of HF pre- and post-HD in ESRD using the current guidelines. METHODS: We prospectively investigated HF in ESRD patients on HD using echocardiography pre- and post-HD. We used the structural and functional abnormality criteria of the 2021 European Society of Cardiology guidelines. RESULTS: A total of 54 patients were enrolled. The mean age was 62.6 years, and 40.1% were male. Forty-five patients (83.3%) had hypertension, 28 (51.9%) had diabetes, and 20 (37.0%) had ischemic heart disease. The mean N-terminal-pro brain natriuretic peptide BNP (NT-proBNP) level was 12,388.8 ± 2,592.2 pg/dL. The mean ideal body weight was 59.3 kg, mean hemodialysis time was 237.4 min, and mean real filtration was 2.8 kg. The mean left ventricular ejection fraction (LVEF) was 62.4%, and mean left ventricular end-diastolic diameter was 52.0 mm in pre-HD. Post-HD echocardiography showed significantly lower left atrial volume index (33.3 ± 15.9 vs. 40.6 ± 17.1, p = 0.030), tricuspid regurgitation jet V (2.5 ± 0.4 vs. 2.8 ± 0.4 m/s, p < 0.001), and right ventricular systolic pressure (32.1 ± 10.3 vs. 38.4 ± 11.6, p = 0.005) compared with pre-HD. There were no differences in LVEF, E/E' ratio, or left ventricular global longitudinal strain. A total of 88.9% of pre-HD patients and 66.7% of post-HD patients had either structural or functional abnormalities in echocardiographic parameters according to recent HF guidelines (p = 0.007). CONCLUSIONS: Our data showed that the majority of patients undergoing hemodialysis satisfy the diagnostic criteria for HF according to current HF guidelines. Pre-HD patients had a 22.2% higher incidence in the prevalence of functional or structural abnormalities as compared with post-HD patients.

12.
World J Clin Cases ; 12(17): 3183-3187, 2024 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-38898834

RESUMEN

BACKGROUND: Primary ciliary dyskinesia (PCD) is an inherited autosomal-recessive disorder of impaired mucociliary clearance characterized by chronic respiratory diseases, otolaryngological diseases, central nervous system abnormalities, reproductive system abnormalities, and cardiac function abnormalities. General anesthesia in these patients is associated with a higher incidence of respiratory complications than in patients without the disease. CASE SUMMARY: A 16-year-old male patient was referred to the emergency room complaining of right ankle pain due to distal tibiofibular fracture. Three years prior, he had been diagnosed with PCD. At that time, he had experienced several episodes of pneumonia, sinusitis, and chronic middle ear infections, for which he underwent surgical interventions. At the current admission, he presented with cough and sputum but no other respiratory symptoms. A chest computed tomography scan revealed centrilobular ground-glass opacities in both lower lobes and a calcified nodule in the left lower lobe. For the surgical procedure and postoperative pain management, combined spinal-epidural anesthesia was employed. The patient's postoperative pain score was measured by the numerical rating scale (NRS). On the day of surgery, his NRS was 5 points. By the second postoperative day, the NRS score had decreased to 2-3 points. The epidural catheter was removed on the fourth day following the operation. The patient was subsequently discharged no respiratory complications. CONCLUSION: We performed combined spinal-epidural anesthesia in a patient with PCD. The patient experienced no additional respiratory complications and was discharged with a low NRS score for pain.

13.
BMC Public Health ; 24(1): 1577, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38867237

RESUMEN

BACKGROUND: Although one's socioeconomic status affects health outcomes, limited research explored how South Korea's National Health Insurance (NHI) system affects mortality rates. This study investigated whether health insurance type and insurance premiums are associated with mortality. METHODS: Based on the National Health Insurance Service-Health Screening cohort, 246,172 men and 206,534 women aged ≥ 40 years at baseline (2002-2003) were included and followed until 2019. Health insurance type was categorized as employee-insured (EI) or self-employed-insured (SI). To define low, medium, and high economic status groups, we used insurance premiums at baseline. Death was determined using the date and cause of death included in the cohort. Cox proportional hazard models were used to analyze the association between insurance factors and the overall and cause-specific mortality. RESULTS: The SI group had a significantly higher risk of overall death compared to the EI group (adjusted hazard ratio (HR) [95% confidence interval]: 1.13 [1.10-1.15] for men and 1.18 [1.15-1.22] for women), after adjusting for various factors. This trend extended to death from the five major causes of death in South Korea (cancer, cardiovascular disease, cerebrovascular disease, pneumonia, and intentional self-harm) and from external causes, with a higher risk of death in the SI group (vs. the EI group). Further analysis stratified by economic status revealed that individuals with lower economic status faced higher risk of overall death and cause-specific mortality in both sexes, compared to those with high economic status for both health insurance types. CONCLUSION: This nationwide study found that the SI group and those with lower economic status faced higher risk of overall mortality and death from the five major causes in South Korea. These findings highlight the potential disparities in health outcomes within the NHI system. To address these gaps, strategies should target risk factors for death at the individual level and governments should incorporate such strategies into public health policy development at the population level. TRIAL REGISTRATION: This study was approved by the Institutional Review Board of Chungbuk National University Hospital (CBNUH-202211-HR-0236) and adhered to the principles of the Declaration of Helsinki (1975).


Asunto(s)
Causas de Muerte , Programas Nacionales de Salud , Humanos , República de Corea , Masculino , Femenino , Persona de Mediana Edad , Adulto , Estudios de Cohortes , Anciano , Mortalidad/tendencias , Seguro de Salud/estadística & datos numéricos , Disparidades en Atención de Salud
14.
Anim Cells Syst (Seoul) ; 28(1): 303-314, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38868077

RESUMEN

The system forming ovarian follicles is developed to investigate in vitro folliculogenesis in a confined environment to obtain functional oocytes. Several studies have reported the successful generation of fully functional oocytes using mouse-induced pluripotent stem cells (iPSCs) and mouse female germline stem cells (fGSCs) as sources of stem cells for in vitro gametogenesis models. In addition, human oogonia have been generated through heterologous co-culture of differentiated human primordial germ cell-like cells (hPGCLCs) with mouse germline somatic cells, although oocyte formation remains challenging. Thus, studies on in vitro ovarian formation in other species are utilized as an introductory approach for in vitro mammalian gametogenesis by understanding the differences in culture systems between species and underlying mechanisms. In this study, we optimized the method of the entire oogenesis process from rat embryonic gonads. We identified well-maturated MII oocytes from rat gonads using our constructed method. Moreover, we generated the first successful in vitro reconstitution of xenogeneic follicles from mouse primordial germ cells (PGCs) and rat somatic cells. We also established an appropriate culture medium and incubation period for xenogeneic follicles. This method will be helpful in studies of xenogeneic follicular development and oocyte generation.

15.
ACS Synth Biol ; 13(7): 2188-2198, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-38912892

RESUMEN

Metabolically engineered microbial consortia can contribute as a promising production platform for the supply of polyamide monomers. To date, the biosynthesis of long-chain α,ω-diamines from n-alkanes is challenging because of the inert nature of n-alkanes and the complexity of the overall synthesis pathway. We combined an engineered Yarrowia lipolytica module with Escherichia coli modules to obtain a mixed strain microbial consortium that could catalyze an efficient biotransformation of n-alkanes into corresponding α,ω-diamines. The engineered Y. lipolytica strain was constructed (YALI10) wherein the two genes responsible for ß-oxidation and the five genes responsible for the overoxidation of fatty aldehydes were deleted. This newly constructed YALI10 strain expressing transaminase (TA) could produce 0.2 mM 1,12-dodecanediamine (40.1 mg/L) from 10 mM n-dodecane. The microbial consortia comprising engineered Y. lipolytica strains for the oxidation of n-alkanes (OM) and an E. coli amination module (AM) expressing an aldehyde reductase (AHR) and transaminase (TA) improved the production of 1,12-diamine up to 1.95 mM (391 mg/L) from 10 mM n-dodecane. Finally, combining the E. coli reduction module (RM) expressing a carboxylic acid reductase (CAR) and an sfp phosphopantetheinyl transferase with OM and AM further improved the production of 1,12-diamine by catalyzing the reduction of undesired 1,12-diacids into 1,12-diols, which further undergo amination to give 1,12-diamine as the target product. This newly constructed mixed strain consortium comprising three modules in one pot gave 4.1 mM (41%; 816 mg/L) 1,12-diaminododecane from 10 mM n-dodecane. The whole-cell consortia reported herein present an elegant "greener" alternative for the biosynthesis of various α,ω-diamines (C8, C10, C12, and C14) from corresponding n-alkanes.


Asunto(s)
Alcanos , Biocatálisis , Diaminas , Escherichia coli , Ingeniería Metabólica , Yarrowia , Yarrowia/metabolismo , Yarrowia/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Alcanos/metabolismo , Ingeniería Metabólica/métodos , Diaminas/metabolismo , Transaminasas/metabolismo , Transaminasas/genética , Oxidación-Reducción , Consorcios Microbianos/genética
16.
Aliment Pharmacol Ther ; 60(3): 389-400, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38866064

RESUMEN

BACKGROUND: The impact of continuing or stopping 5-aminosalicylates (5-ASA) after commencing anti-tumour necrosis factor (anti-TNF) therapy in patients with inflammatory bowel disease (IBD) remains unclear. AIMS: To compare the outcomes of patients with IBD who stopped or continued 5-ASA after starting anti-TNF therapy. METHODS: We analysed data from the Korean National Health Insurance claims database between 2007 and 2020. We compared the clinical outcomes of patients who stopped or continued 5-ASA within 90 days of anti-TNF initiation. The primary outcome was any adverse clinical event defined as a composite of new corticosteroid use, IBD-related hospitalisation, or intestinal surgery. RESULTS: Among 7442 patients included for analysis (4479 [60.2%] with Crohn's disease [CD] and 2963 [39.8%] with ulcerative colitis [UC]), 1037 (13.9%) discontinued 5-ASA within 90 days of starting anti-TNF therapy. During a median 4.3-year follow-up, discontinuation of 5-ASA was not associated with an increased risk of adverse clinical events (adjusted hazard ratio 1.01, 95% confidence interval 0.93-1.10). The cumulative incidence of each adverse clinical event and the composite outcome were not significantly different between groups (all, p > 0.05). Additionally, separate analyses in CD and UC cohorts revealed no differences in adverse clinical outcomes between the 5-ASA continuation and discontinuation groups. Subgroup analyses by presumed risk factors for disease relapse showed no significant differences in the risk of adverse events between groups. CONCLUSIONS: In this nationwide population-based study, discontinuing 5-ASA after starting anti-TNF therapy was not associated with an increased risk of adverse events in patients with IBD.


Asunto(s)
Mesalamina , Humanos , Femenino , Masculino , Adulto , Mesalamina/uso terapéutico , Mesalamina/efectos adversos , Persona de Mediana Edad , República de Corea/epidemiología , Enfermedad de Crohn/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Antiinflamatorios no Esteroideos/uso terapéutico , Antiinflamatorios no Esteroideos/efectos adversos , Colitis Ulcerosa/tratamiento farmacológico , Adulto Joven , Anciano , Estudios Retrospectivos
17.
Exp Mol Med ; 56(6): 1365-1372, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38825646

RESUMEN

Inside germinal centers (GCs), antigen-specific B cells rely on precise interactions with immune cells and strategic localization between the dark and light zones to clonally expand, undergo affinity maturation, and differentiate into long-lived plasma cells or memory B cells. Follicular helper T (Tfh) cells, the key gatekeepers of GC-dependent humoral immunity, exhibit remarkable dynamic positioning within secondary lymphoid tissues and rely on intercellular interactions with antigen-presenting cells (APCs) during their differentiation and execution of B-cell-facilitating functions within GCs. In this review, we briefly cover the transcriptional regulation of Tfh cell differentiation and function and explore the molecular mechanisms governing Tfh cell motility, their interactions with B cells within GCs, and the impact of their dynamic behavior on humoral responses.


Asunto(s)
Regulación de la Expresión Génica , Centro Germinal , Sinapsis Inmunológicas , Humanos , Animales , Sinapsis Inmunológicas/metabolismo , Centro Germinal/inmunología , Centro Germinal/metabolismo , Diferenciación Celular , Linfocitos B/inmunología , Linfocitos B/metabolismo , Células T Auxiliares Foliculares/inmunología , Células T Auxiliares Foliculares/metabolismo , Transcripción Genética , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Colaboradores-Inductores/metabolismo
18.
JBMR Plus ; 8(7): ziae056, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38855796

RESUMEN

Large-scale studies on the risk of fragility fractures in patients with primary biliary cholangitis (PBC) are limited due to low incidence. We aimed to investigate whether PBC is associated with fragility fractures using real-world nationwide data. The Korean National Health Insurance Service claims data from 2007 to 2020 were analyzed in this population-based cohort study. Patients with PBC (n = 4951) were matched with controls (n = 19 793) using a 1:4 ratio based on age, sex, and follow-up duration. The primary outcome was fragility fracture, which comprised fractures of the vertebra, hip, distal radius, and proximal humerus. The incidence rates (IRs) and hazard ratios (HRs) were determined to assess the impact of PBC on fragility fractures. During the median follow-up period of 5.37 years, 524 patients in the PBC group had fragility fractures (IR, 18.59/1000 person-years [PYs]). After adjusting for covariates, PBC increased the risk of fragility fractures by 1.63-fold (95% confidence interval, 1.20-2.22; P = .002). The vertebra and hip were particularly susceptible to fracture in patients with PBC, with adjusted HRs of 1.77 and 2.23, respectively. In the subgroup analysis, the risk of fragility fracture was 2.53-fold higher in men and 1.59-fold higher in women with PBC than that in the respective matched control groups. Considering the morbidity and mortality related to fragility fractures, increasing awareness of fragility fracture risk and implementing appropriate preventive measures in patients with PBC are imperative.

19.
Clin Transplant Res ; 38(1): 1-6, 2024 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-38725179

RESUMEN

Following kidney transplantation, antibody-mediated rejection (AMR) occurs when the antibodies of the immune system attack the transplanted organ, leading to damage of the kidney tissue. De novo human leukocyte antigen donor-specific antibodies (HLA-DSAs) play a key role in AMR. Current therapeutic approaches include intravenous immunoglobulin, anti-CD20 antibodies, and plasmapheresis. In cases resistant to treatment, proteasome inhibitors and C5 inhibitors may be employed. Nevertheless, a pressing need exists for new medications to improve transplant survival and reduce complications. In the context of AMR, interleukin (IL)-6 is instrumental in the development and maturation of B cells into plasma cells, which then produce HLA-DSAs targeting the allograft. IL-6 inhibitors are currently under investigation and show promise due to the essential role of IL-6 in the immune response; however, additional research is necessary.

20.
Discov Med ; 36(184): 1002-1011, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38798259

RESUMEN

BACKGROUND: Tuberculosis (TB) is still the main cause of mortality due to a single transfectant, Mycobacterium tuberculosis (MTB). Latent tuberculosis infection (LTBI) is a condition characterized by the presence of tuberculosis (TB) that is not clinically apparent but nonetheless shows a sustained response to MTB. Presently, tuberculin skin test (TST) and interferon gamma (IFN-γ) release assays (IGRAs) are mainly used to detect LTBI via cell-mediated immunity of T-cells. For people with end-stage renal disease (ESRD), the diagnosis of patients infected with MTB is difficult because of T-cell dysfunction. To get more accurate diagnosis results of LTBI, it must compensate for the deficiency of IGRA tests. METHODS: Sixty-seven hemodialysis (HD) patients and 96 non-HD patients were enrolled in this study and the study population is continuously included. IFN-γ levels were measured by the QuantiFERON-TB Gold In-Tube (QFT-GIT) test. Kidney function indicators, blood urea nitrogen (BUN), serum creatinine (Cr), and estimated glomerular filtration rate (eGFR) were used to compensate for the declined IFN-γ levels in the IGRA test. RESULTS: In individuals who were previously undetected, the results of compensation with serum Cr increased by 10.81%, allowing for about 28% more detection, and compensation with eGFR increased by 5.41%, allowing for approximately 14% more detectable potential among them and employing both of them could enhance the prior shortcomings of IGRA tests. when both are used, the maximum compensation results show a sensitivity increase rate of 8.81%, and approximately 23% of patients who were previously undetectable may be found. CONCLUSION: Therefore, the renal function markers which are routine tests for HD patients to compensate for the deficiency of IGRA tests could increase the accuracy of LTBI diagnosis.


Asunto(s)
Ensayos de Liberación de Interferón gamma , Fallo Renal Crónico , Tuberculosis Latente , Diálisis Renal , Humanos , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/inmunología , Tuberculosis Latente/sangre , Masculino , Femenino , Persona de Mediana Edad , Diálisis Renal/efectos adversos , Ensayos de Liberación de Interferón gamma/métodos , Fallo Renal Crónico/terapia , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/sangre , Fallo Renal Crónico/inmunología , Anciano , Interferón gamma/sangre , Adulto , Reacciones Falso Negativas , Tasa de Filtración Glomerular , Creatinina/sangre , Mycobacterium tuberculosis/inmunología , Prueba de Tuberculina/métodos , Nitrógeno de la Urea Sanguínea
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