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1.
J Rheum Dis ; 31(3): 135-142, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38957367

ABSTRACT

Pediatric vasculitis and adult vasculitis differ in several aspects. While both involve inflammation of blood vessels, pediatric vasculitis tends to present with distinct clinical features and may involve different types of blood vessels compared to adult vasculitis. Despite its relatively rare occurrence compared to adult vasculitis, pediatric vasculitis warrants careful attention due to its potential for profound and diverse clinical manifestations, ranging from mild cutaneous symptoms to life-threatening systemic complications. Childhood vasculitis should be suspected in children who present symptoms attributable to systemic inflammation and complications arising from multi-organ dysfunction. However, achieving a diagnosis necessitates thorough exclusion of alternative conditions manifesting similar symptoms and findings. Hence, children suspected of vasculitis should undergo meticulous history-taking, comprehensive physical examination, and requisite laboratory investigations, imaging studies, and sometimes tissue biopsies to elucidate the diagnosis. Early detection and treatment of childhood vasculitis are crucial, as the condition can affect various organs and potentially lead to life-threatening complications or long-term sequelae in adulthood if left untreated. This review aimed to provide an exhaustive overview of childhood vasculitis, outlining its epidemiology, classification, clinical presentation, diagnostic modalities, therapeutic strategies and outcome.

2.
Int J Mol Sci ; 25(13)2024 Jun 30.
Article in English | MEDLINE | ID: mdl-39000355

ABSTRACT

Postmenopausal osteoporosis, characterized by an imbalance between osteoclast-mediated bone resorption and osteoblast-driven bone formation, presents substantial health implications. In this study, we investigated the role of black goat extract (BGE), derived from a domesticated native Korean goat, estrogen-like activity, and osteoprotective effects in vitro. BGE's mineral and fatty acid compositions were analyzed via the ICP-AES method and gas chromatography-mass spectrometry, respectively. In vitro experiments were conducted using MCF-7 breast cancer cells, MC3T3-E1 osteoblasts, and RAW264.7 osteoclasts. BGE exhibits a favorable amount of mineral and fatty acid content. It displayed antimenopausal activity by stimulating MCF-7 cell proliferation and augmenting estrogen-related gene expression (ERα, ERß, and pS2). Moreover, BGE positively impacted osteogenesis and mineralization in MC3T3-E1 cells through Wnt/ß-catenin pathway modulation, leading to heightened expression of Runt-related transcription factor 2, osteoprotegerin, and collagen type 1. Significantly, BGE effectively suppressed osteoclastogenesis by curtailing osteoclast formation and activity in RAW264.7 cells, concurrently downregulating pivotal signaling molecules, including receptor activator of nuclear factor κ B and tumor necrosis factor receptor-associated factor 6. This study offers a shred of preliminary evidence for the prospective use of BGE as an effective postmenopausal osteoporosis treatment.


Subject(s)
Cell Differentiation , Goats , Osteoblasts , Osteoclasts , Osteogenesis , Animals , Mice , RAW 264.7 Cells , Osteoblasts/drug effects , Osteoblasts/metabolism , Osteogenesis/drug effects , Cell Differentiation/drug effects , Osteoclasts/drug effects , Osteoclasts/metabolism , Osteoclasts/cytology , Humans , Estrogens/pharmacology , Cell Proliferation/drug effects , Wnt Signaling Pathway/drug effects , MCF-7 Cells , Tissue Extracts/pharmacology
3.
J Thorac Dis ; 16(6): 3818-3827, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38983157

ABSTRACT

Background: Radial endobronchial ultrasound (rEBUS) guide sheath (GS) transbronchial lung biopsy (TBLB) improves the diagnostic yield of peripheral lung lesions (PLL). However, its diagnostic yield is approximately 60%. We aimed to evaluate the diagnostic utility of adding rEBUS GS transbronchial needle aspiration (TBNA) using PeriView FLEX needle (Olympus, Tokyo, Japan) to rEBUS GS TBLB. Methods: In this retrospective study, we initially screened 124 PLLs in 123 patients who underwent rEBUS GS procedures for PLLs from December 2020 to August 2021. The analysis was performed on 74 PLLs in 73 patients who underwent both rEBUS GS TBLB and TBNA. Results: PLLs showed the following characteristics: lesion size [mean ± standard deviation (SD)], 24±12 mm; nature (solid vs. subsolid), 59 (79.7%) vs. 15 (20.3%); distance from the pleura (mean ± SD), 14±14 mm; rEBUS visualization type (probe within PLL vs. probe adjacent to PLL), 56 (75.7%) vs. 18 (24.3%). Among 74 PLLs, 47 (63.5%) were successfully diagnosed by rEBUS GS TBLB. In 27 PLLs not diagnosed by rEBUS GS TBLB, 5 (18.5%) were further diagnosed by rEBUS GS TBNA [overall diagnostic yield: 70.3% (52/74)]. EBUS visualization type of "probe adjacent to PLL" was a significant factor associated with the diagnostic yield of additional rEBUS GS TBNA. Conclusions: In rEBUS GS procedures for PLLs, the diagnostic yield might be improved by implementing TBNA in addition to TBLB. In particular, additional TBNA is preferable if the probe is adjacent to the lesion rather than within the lesion on rEBUS.

4.
Front Med (Lausanne) ; 11: 1349577, 2024.
Article in English | MEDLINE | ID: mdl-38841588

ABSTRACT

Background: In patients undergoing percutaneous coronary intervention (PCI), the use of anti-inflammatory therapy with colchicine is associated with a reduction of recurrent ischemic events. The mechanisms of such findings are not fully elucidated. Objectives: To investigate the effects of colchicine versus aspirin on inflammation and platelet reactivity in patients with acute coronary syndrome (ACS) undergoing PCI. Methods: This observational study compared laboratory measurements in ACS patients receiving single antiplatelet therapy with ticagrelor or prasugrel plus colchicine (MACT) (n = 185) versus conventional dual-antiplatelet therapy (DAPT) with aspirin plus ticagrelor or prasugrel (n = 497). The primary outcome was the frequency of high residual inflammation, defined as high-sensitivity C-reactive protein (hs-CRP) ≥2 mg/L at 1 month post-PCI. Multiple sensitivity analyses were performed for the primary outcome, including multivariable adjustment, propensity-score matching, and inverse-probability weighted methods. Results: One month after PCI, patients treated with MACT had significantly lower levels of hs-CRP compared to those treated with DAPT (0.6 [0.4-1.2] vs. 0.9 [0.6-2.3] mg/L, p < 0.001). The frequency of high residual inflammation was also lower in the MACT group (10.8% vs. 27.2%, p < 0.001) (odds ratio [95% confidence interval] = 0.33 [0.20-0.54], p < 0.001). This effect was consistent across sensitivity analyses. There was no difference in platelet reactivity between MACT and DAPT (49.6 ± 49.0 vs. 51.5 ± 66.4 P2Y12 reaction unit [PRU] measured by VerifyNow, p = 0.776). Conclusion: In ACS patients undergoing PCI, MACT was associated with a lower rate of high residual inflammation without increasing platelet reactivity compared to conventional DAPT. Clinical trial registration: NCT04949516 for MACT pilot trial and NCT04650529 for Gyeongsang National University Hospital registry.

5.
Front Med (Lausanne) ; 11: 1384981, 2024.
Article in English | MEDLINE | ID: mdl-38912344

ABSTRACT

Objective: The long-term clinical effect of arterial stiffness in high-risk disease entities remains unclear. The prognostic implications of brachial-ankle pulse wave velocity (baPWV) were assessed using a real-world registry that included patients who underwent percutaneous coronary intervention (PCI). Methods: Arterial stiffness was measured using baPWV before discharge. The primary outcome was net adverse clinical events (NACE), defined as a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, or major bleeding. Secondary outcomes included major adverse cardiac and cerebrovascular events (MACCE: a composite of all-cause death, non-fatal myocardial infarction, or non-fatal stroke), and major bleeding. The outcomes were assessed over a 4-year period. Results: Patients (n = 3,930) were stratified into high- and low-baPWV groups based on a baPWV cut-off of 1891 cm/s determined through time-dependent receiver operating characteristic curve analysis. baPWV was linearly correlated with 4-year post-PCI clinical events. The high baPWV group had a greater cumulative incidence of NACE, MACCE, and major bleeding. According to multivariable analysis, the high baPWV groups had a significantly greater risk of 4-year NACE (adjusted hazard ratio [HRadj]: 1.44; 95% confidence interval [CI]: 1.12-1.85; p = 0.004), MACCE (HRadj: 1.40; 95% CI: 1.07-1.83; p = 0.015), and major bleeding (HRadj: 1.94; 95% CI: 1.15-3.25; p = 0.012). Conclusion: In PCI-treated patients, baPWV was significantly associated with long-term clinical outcomes, including ischemic and bleeding events, indicating its value for identifying high-risk phenotypes.

6.
Eur Heart J ; 45(25): 2217-2231, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38804262

ABSTRACT

BACKGROUND AND AIMS: Platelet-fibrin clot strength (PFCS) is linked to major adverse cardiovascular event (MACE) risk. However, the association between PFCS and platelet reactivity and their prognostic implication remains uncertain in patients undergoing percutaneous coronary intervention (PCI). METHODS: In PCI-treated patients (n = 2512) from registry data from January 2010 to November 2018 in South Korea, PFCS using thromboelastography and platelet reactivity using VerifyNow were measured. High PFCS (PFCSHigh) was defined as thromboelastography maximal amplitude ≥ 68 mm, and high platelet reactivity (HPR) was defined as >208 P2Y12 reaction units. Patients were stratified into four groups according to maximal amplitude and P2Y12 reaction unit levels: (i) normal platelet reactivity (NPR)-PFCSNormal (31.8%), (ii) HPR-PFCSNormal (29.0%), (iii) NPR-PFCSHigh (18.1%), and (iv) HPR-PFCSHigh (21.1%). Major adverse cardiovascular event (all-cause death, myocardial infarction, or stroke) and major bleeding were followed up to 4 years. RESULTS: High platelet reactivity and PFCSHigh showed an additive effect for clinical outcomes (log-rank test, P < .001). Individuals with NPR-PFCSNormal, NPR-PFCSHigh, HPR-PFCSNormal, and HPR-PFCSHigh demonstrated MACE incidences of 7.5%, 12.6%, 13.4%, and 19.3%, respectively. The HPR-PFCSHigh group showed significantly higher risks of MACE compared with the NPR-PFCSNormal group [adjusted hazard ratio (HRadj) 1.89; 95% confidence interval (CI) 1.23-2.91; P = .004] and the HPR-PFCSNormal group (HRadj 1.60; 95% CI 1.12-2.27; P = .009). Similar results were observed for all-cause death. Compared with HPR-PFCSNormal phenotype, NPR-PFCSNormal phenotype was associated with a higher risk of major bleeding (HRadj 3.12; 95% CI 1.30-7.69; P = .010). CONCLUSIONS: In PCI patients, PFCS and platelet reactivity demonstrated important relationships in predicting clinical prognosis. Their combined assessment may enhance post-PCI risk stratification for personalized antithrombotic therapy.


Subject(s)
Blood Platelets , Percutaneous Coronary Intervention , Thrombelastography , Humans , Percutaneous Coronary Intervention/adverse effects , Male , Female , Middle Aged , Aged , Republic of Korea/epidemiology , Fibrin/metabolism , Platelet Activation/physiology , Prognosis , Myocardial Infarction/blood , Myocardial Infarction/epidemiology
8.
Small Methods ; : e2400063, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38721963

ABSTRACT

2D covalent organic frameworks (COFs) are highly porous crystalline materials with promising applications in organic electronics. Current methods involve either on-surface synthesis (solid surface) or interfacial synthesis (liquid/liquid, liquid/gas interface) to create thin films for these applications, each with its drawbacks. On-surface synthesis can lead to contamination from COF powder or unreacted chemicals, while interfacial synthesis risks damaging the film during post-transfer processes. These challenges necessitate the development of alternative synthesis methods for high-quality 2D COF films. This study presents a novel approach for synthesizing homogeneous 2D COF thin films by combining photochemistry and a liquid-flowing system. Leveraging previous work on liquid flow systems to prevent contamination during solvothermal synthesis, this approach to the photochemical method, resulting in the synthesis of high-crystalline 2D COF films with tunable thickness is adopted. The photochemical approach offers spatially controllable energy sources, enabling patternable COF synthesis. Notably, it is successfully fabricated ultrasmooth patterned 2D COF films on hexagonal boron nitride, offering a streamlined process for optoelectronic device fabrication without additional pre, post-processing steps.

9.
Adv Mater ; : e2400261, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38741451

ABSTRACT

Intracranial implants for diagnosis and treatment of brain diseases have been developed over the past few decades. However, the platform of conventional implantable devices still relies on invasive probes and bulky sensors in conjunction with large-area craniotomy and provides only limited biometric information. Here, an implantable multi-modal sensor array that can be injected through a small hole in the skull and inherently spread out for conformal contact with the cortical surface is reported. The injectable sensor array, composed of graphene multi-channel electrodes for neural recording and electrical stimulation and MoS2-based sensors for monitoring intracranial temperature and pressure, is designed based on a mesh structure whose elastic restoring force enables the contracted device to spread out. It is demonstrated that the sensor array injected into a rabbit's head can detect epileptic discharges on the surface of the cortex and mitigate it by electrical stimulation while monitoring both intracranial temperature and pressure. This method provides good potential for implanting a variety of functional devices via minimally invasive surgery.

10.
Science ; 384(6693): 312-317, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38669572

ABSTRACT

Electrostatic capacitors are foundational components of advanced electronics and high-power electrical systems owing to their ultrafast charging-discharging capability. Ferroelectric materials offer high maximum polarization, but high remnant polarization has hindered their effective deployment in energy storage applications. Previous methodologies have encountered problems because of the deteriorated crystallinity of the ferroelectric materials. We introduce an approach to control the relaxation time using two-dimensional (2D) materials while minimizing energy loss by using 2D/3D/2D heterostructures and preserving the crystallinity of ferroelectric 3D materials. Using this approach, we were able to achieve an energy density of 191.7 joules per cubic centimeter with an efficiency greater than 90%. This precise control over relaxation time holds promise for a wide array of applications and has the potential to accelerate the development of highly efficient energy storage systems.

11.
Curr Issues Mol Biol ; 46(4): 3328-3341, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38666938

ABSTRACT

Kidney cancer has emerged as a major medical problem in recent times. Multiple compounds are used to treat kidney cancer by triggering cancer-causing gene targets. For instance, isoquercitrin (quercetin-3-O-ß-d-glucopyranoside) is frequently present in fruits, vegetables, medicinal herbs, and foods and drinks made from plants. Our previous study predicted using protein-protein interaction (PPI) and molecular docking analysis that the isoquercitrin compound can control kidney cancer and inflammation by triggering potential gene targets of IGF1R, PIK3CA, IL6, and PTGS2. So, the present study is about further in silico and in vitro validation. We performed molecular dynamic (MD) simulation, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, cytotoxicity assay, and RT-PCR and qRT-PCR validation. According to the MD simulation (250 ns), we found that IGF1R, PIK3CA, and PTGS2, except for IL6 gene targets, show stable binding energy with a stable complex with isoquercitrin. We also performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the final targets to determine their regulatory functions and signaling pathways. Furthermore, we checked the cytotoxicity effect of isoquercitrin (IQ) and found that 5 µg/mL and 10 µg/mL doses showed higher cell viability in a normal kidney cell line (HEK 293) and also inversely showed an inhibition of cell growth at 35% and 45%, respectively, in the kidney cancer cell line (A498). Lastly, the RT-PCR and qRT-PCR findings showed a significant decrease in PTGS2, PIK3CA, and IGF1R gene expression, except for IL6 expression, following dose-dependent treatments with IQ. Thus, we can conclude that isoquercitrin inhibits the expression of PTGS2, PIK3CA, and IGF1R gene targets, which in turn controls kidney cancer and inflammation.

12.
Gland Surg ; 13(3): 340-350, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38601290

ABSTRACT

Background: The changing medical education environment emphasizes the need for time efficiency, increasing the demand for competency-based medical education to improve trainees' learning strategies. This study was performed to determine the competencies required for successful performance of robotic thyroidectomy (RT) and to determine the consensus of experts for performance of RT. Methods: Data were collected through 12 semi-structured interviews with RT experts and 11 field observations. Cognitive task analysis was performed to determine the competencies required for experts to perform RT. A modified Delphi methodology was used to determine how 20 experts rated the importance of each item of RT performance on a Likert 7-point scale. The criteria for the Delphi consensus were set at a Cronbach's α≥0.80 with two survey rounds. Results: After 11 field observations and 12 semi-structured interviews, 89 items were identified within six modules. These items were grouped into sub-modules according to their theme. The modified Delphi survey, involving 21 experts, reached the consensus standard during the second round (Cronbach's α=0.954), enabling the identification of the 64 most important items within six modules related to RT performance: midline incision to isthmectomy (MID module; n=8), lateral dissection (LAT module; n=7), preservation of inferior parathyroid glands (INF module; n=16), preservation of recurrent laryngeal nerve and dissection of the ligament of Berry (BER module; n=21), dissection of the thyroid upper pole (SUP module; n=10), and specimen removal and closure (END module; n=2). Conclusions: This mixed-method study combining qualitative and quantitative methodology identified modules of core competencies required to perform RT. These modules can be used as a standard and objective guide to train surgeons to perform RT and evaluate outcomes.

13.
Brain Impair ; 252024 Mar.
Article in English | MEDLINE | ID: mdl-38566285

ABSTRACT

Background Exercise is crucial for the well-being of people with Parkinson's disease (PD). Although there are challenges to exercising with PD, mobile apps are seen as potential solutions, though their impact is not yet fully understood. We developed a mobile app and a home-based exercise program specialised for people with PD and investigated the effect of the mobile exercise app for the people with PD. Methods Participants from the Movement Disorder Clinic were prompted to download and actively use our app for a duration of 2 weeks. Before commencing, we assessed their self-rated smartphone proficiency. Both at the start and after the 2-week period, we employed the International Physical Activity Questionnaire-Short Form and the PD Questionnaire-39 (PDQ-39) to evaluate their physical activity and overall quality of life (QoL). Exercise metrics were quantified in terms of metabolic equivalent minutes per week (MET-min/week). Furthermore, we gathered feedback on user satisfaction with the app at the end of the study. Results Out of 41 recruited patients, 25 completed the 2-week program and 16 dropped out. Median MET-min/week rose from 1386.0 to 3210.0 (P = 0.009), primarily in moderate activities (P = 0.049) and walking (P = 0.002). Median PDQ-39 scores showed improvement from 17.2 to 8.5 (P = 0.005) after the program. Conclusion The mobile app holds potential to enhance exercise and QoL for people with PD. For optimal benefits, future studies should focus on e-health literacy education, app quality enhancements, and a broader exercise program variety.


Subject(s)
Mobile Applications , Parkinson Disease , Humans , Pilot Projects , Quality of Life , Parkinson Disease/therapy , Exercise
14.
Int J Rheum Dis ; 27(4): e15144, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38590055

ABSTRACT

BACKGROUND: Infections are considered risk factors for autoimmune inflammatory rheumatic diseases (AIRDs), the incidence of which is considered to have been impacted by the COVID-19 pandemic. The impact of non-pharmaceutical interventions (NPIs) on the incidence of AIRDs and their associated health care services and medical expenses in Korea was investigated. METHODS: We included all AIRD cases reported between January 2016 and February 2021 based on the National Health Insurance Service data. We evaluated changes in incidence trends for each AIRD before and after NPI implementation (Feb 2020 to Feb 2021) using segmented regression analysis. Changes in health care utilization and medical costs for each AIRD before and after NPI implementation were also investigated. RESULTS: After NPI implementation, monthly incidence rates declined significantly by 0.205 per 1 000 000 (95% confidence interval [CI], -0.308 to -0.101, p < .001) in patients with systemic lupus erythematosus (SLE). No significant changes in the incidence of all AIRDs other than SLE were observed before and after implementation. Further, annual outpatient department visits per patient were lower during implementation for all diseases, except juvenile idiopathic arthritis (JIA). The prescription days per outpatient visit increased significantly during implementation for all diseases, except JIA and ankylosing spondylitis. During implementation, the total annual medical costs per patient tended to decrease for all diseases, except JIA and mixed connective tissue disease. CONCLUSION: Implementation of NPIs to contain the pandemic led to a reduction in the incidence of SLE and changed patterns of medical care utilization and treatment cost for most AIRDs.


Subject(s)
Arthritis, Juvenile , Autoimmune Diseases , COVID-19 , Lupus Erythematosus, Systemic , Rheumatic Diseases , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Incidence , Pandemics , Arthritis, Juvenile/epidemiology , Cost of Illness , Republic of Korea/epidemiology , Rheumatic Diseases/diagnosis , Rheumatic Diseases/epidemiology , Rheumatic Diseases/therapy , Autoimmune Diseases/diagnosis , Autoimmune Diseases/epidemiology , Autoimmune Diseases/therapy
15.
Coron Artery Dis ; 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38595079

ABSTRACT

BACKGROUND: Cilostazol has a vasodilatory function that may be beneficial for patients with vasospastic angina (VSA). We conducted a randomized, open-label, controlled trial to compare the efficacy and safety of long-acting cilostazol and isosorbide mononitrate (ISMN) for VSA. METHODS: The study included patients with confirmed VSA between September 2019 and May 2021. Participants were randomly assigned to receive long-acting cilostazol (test group, 200 mg once daily) or conventional ISMN therapy (control group, 20 mg twice daily) for 4 weeks. The clinical efficacy and safety were evaluated using weekly questionnaires. RESULTS: Forty patients were enrolled in the study (long-acting cilostazol, n = 20; ISMN, n = 20). Baseline characteristics were balanced between the two groups. Long acting cilostazol showed better angina symptom control within the first week compared to ISMN [reduction of pain intensity score, 6.0 (4.0-8.0) vs. 4.0 (1.0-5.0), P = 0.005; frequency of angina symptom, 0 (0-2.0) vs. 2.0 (0-3.0), P = 0.027, respectively]. The rate of neurological adverse reactions was lower in the cilostazol group than in the ISMN group (headache or dizziness, 40 vs. 85%, P = 0.009; headache, 30 vs. 70%, P = 0.027). CONCLUSION: Long-acting cilostazol provided comparable control of angina and fewer adverse neurologic reactions within 4 weeks compared to ISMN. Long-acting cilostazol provides more intensive control of angina within 1 week, suggesting that it may be an initial choice for the treatment of VSA.

16.
ACS Pharmacol Transl Sci ; 7(3): 560-569, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38481689

ABSTRACT

Obesity is a well-established risk factor for cancer, significantly impacting both cancer incidence and mortality. However, the intricate molecular mechanisms connecting adipose tissue to cancer cell metabolism are not fully understood. This Review explores the historical context of tumor energy metabolism research, tracing its origins to Otto Warburg's pioneering work in 1920. Warburg's discovery of the "Warburg effect", wherein cancer cells prefer anaerobic glycolysis even in the presence of oxygen, laid the foundation for understanding cancer metabolism. Building upon this foundation, the "reverse Warburg effect" emerged in 2009, elucidating the role of aerobic glycolysis in cancer-associated fibroblasts (CAFs) and its contribution to lactate accumulation in the tumor microenvironment, subsequently serving as a metabolic substrate for cancer cells. In contrast, within high-adiposity contexts, cancer cells exhibit a unique metabolic shift termed the "inversion of the Warburg effect". This phenomenon, distinct from the stromal-dependent reverse Warburg effect, relies on increased nutrient abundance in obesity environments, leading to the generation of glucose from lactate as a metabolic substrate. This Review underscores the heightened tumor proliferation and aggressiveness associated with obesity, introducing the "inversion of the Warburg effect" as a novel mechanism rooted in the altered metabolic landscape within an obese milieu. The insights presented here open promising avenues for therapeutic exploration, offering fresh perspectives and opportunities for the development of innovative cancer treatment strategies.

17.
Med Sci Monit ; 30: e942899, 2024 Mar 10.
Article in English | MEDLINE | ID: mdl-38509819

ABSTRACT

BACKGROUND The gut microbial metabolites demonstrate significant activity against metabolic diseases including osteoporosis (OP) and obesity, but active compounds, targets, and mechanisms have not been fully identified. Hence, the current investigation explored the mechanisms of active metabolites and targets against OP and obesity by using network pharmacology approaches. MATERIAL AND METHODS The gutMGene database was used to collect gut microbial targets-associated metabolites; DisGeNET and OMIM databases were used to identify targets relevant to OP and obesity. A total of 63 and 89 overlapped targets were considered the final OP and obesity targets after creating a Venn diagram of metabolites-related targets and disease-related targets. Furthermore, the top 20% of degrees, betweenness, and closeness were used to form the sub-network of protein-protein interaction of these targets. Finally, the biotransformation-increased receptors and biological mechanisms were identified and validated using ADMET properties analysis, molecular docking, and molecular dynamic simulation. RESULTS GO, KEGG pathway analysis, and protein-protein interactions were performed to establish metabolites and target networks. According to the enrichment analysis, OP and obesity are highly linked to the lipid and atherosclerosis pathways. Moreover, ADMET analysis depicts that the major metabolites have drug-likeliness activity and no or less toxicity. Following that, the molecular docking studies showed that compound K and TP53 target have a remarkable negative affinity (-8.0 kcal/mol) among all metabolites and targets for both diseases. Finally, the conformity of compound K against the targeted protein TP53 was validated by 250ns MD simulation. CONCLUSIONS Therefore, we summarized that compound K can regulate TP53 and could be developed as a therapy option for OP and obesity.


Subject(s)
Drugs, Chinese Herbal , Gastrointestinal Microbiome , Ginsenosides , Osteoporosis , Humans , Molecular Docking Simulation , Network Pharmacology , Computational Biology , Molecular Dynamics Simulation , Obesity/drug therapy , Osteoporosis/drug therapy
18.
Medicina (Kaunas) ; 60(3)2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38541143

ABSTRACT

Background and Objectives: Peripherally inserted central catheter (PICC) placement plays an important role in clinical practice. This study aimed to provide an equation for the proper estimation of catheter length in cases of PICC placement without imaging guidance in relation to patient height, weight, sex, and age. Materials and Methods: For 1137 PICC placement cases in both arm veins of 954 patients at a single center, the elbow crease to the cavoatrial junction length (ECL) was calculated as follows: ECL = (PICC length) + (distance from the elbow crease to the puncture site). We analyzed the relationship between ECL and patient characteristics and suggested a new equation for ECL based on height, weight, sex, and age. Results: The average ECL was 48.0 ± 2.4 cm in the right side and 51.0 ± 3.0 cm in the left side. ECL in the right arm was significantly correlated with patient height, sex, and age, whereas the ECL in the left arm was additionally significantly correlated with patient weight. The ECL (cm) prediction model was as follows: right ECL = 26.32 + 1.33 × (female = 1, male = 2) - 0.02 × age (years) + 0.13 × height (cm); left ECL = 22.09 + 1.28 × (female = 1, male = 2) + 0.02 × age (years) + 0.14 × height (cm) + 0.042 × weight (kg). Conclusions: The appropriate PICC length was predicted based on the patient's height, weight, sex, and age. The equations in our study can help predict the optimal catheter length and can be automatically calculated using computerized patient information for bedside procedures in PICC.


Subject(s)
Catheterization, Central Venous , Catheterization, Peripheral , Humans , Male , Female , Catheterization, Central Venous/methods , Catheterization, Peripheral/methods , Catheters , Retrospective Studies
19.
Yonsei Med J ; 65(4): 241-245, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38515362

ABSTRACT

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS, OMIM: #142680) is a rare autoinflammatory disease (AID) with recurrent febrile episodes. To our knowledge, we report herein the first case of a patient with TRAPS in South Korea whose symptoms included fever, arthralgia, abdominal pain, rash, myalgia, cough, and lymphadenopathy. A pathogenic de novo mutation, c.175T>C (p.Cys59Arg), in the tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) gene, was confirmed by gene sequencing. The patient has been with tocilizumab (an interleukin-6 inhibitor); tocilizumab administration every other week has completely alleviated the patient's symptoms. Our report further expands the clinical spectrum of patients with TRAPS and reaffirms the use of tocilizumab as a viable alternative treatment option for those patients who are unsatisfactorily responsive to other commonly used biologics, such as canakinumab, anakinra, infliximab, and etanercept. Furthermore, our report may aid in increasing awareness about the existence of mutation-confirmed TRAPS in South Korea in addition to emphasizing the importance of actively pursuing genetic testing to correctly diagnose rare AID.


Subject(s)
Fever , Hereditary Autoinflammatory Diseases , Humans , Fever/complications , Hereditary Autoinflammatory Diseases/diagnosis , Hereditary Autoinflammatory Diseases/drug therapy , Hereditary Autoinflammatory Diseases/genetics , Receptors, Tumor Necrosis Factor, Type I/genetics , Receptors, Tumor Necrosis Factor, Type I/therapeutic use , Mutation , Etanercept/therapeutic use
20.
Nat Commun ; 15(1): 2017, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38443376

ABSTRACT

HIV-1 infection elevates the risk of developing various cancers, including T-cell lymphoma. Whether HIV-1-encoded proteins directly contribute to oncogenesis remains unknown. We observe that approximately 1-5% of CD4+ T cells from the blood of people living with HIV-1 exhibit over-duplicated centrioles, suggesting that centrosome amplification underlies the development of HIV-1-associated cancers by driving aneuploidy. Through affinity purification, biochemical, and cellular analyses, we discover that Vpr, an accessory protein of HIV-1, hijacks the centriole duplication machinery and induces centrosome amplification and aneuploidy. Mechanistically, Vpr forms a cooperative ternary complex with an E3 ligase subunit, VprBP, and polo-like kinase 4 (Plk4). Unexpectedly, however, the complex enhances Plk4's functionality by promoting its relocalization to the procentriole assembly and induces centrosome amplification. Loss of either Vpr's C-terminal 17 residues or VprBP acidic region, the two elements required for binding to Plk4 cryptic polo-box, abrogates Vpr's capacity to induce these events. Furthermore, HIV-1 WT, but not its Vpr mutant, induces multiple centrosomes and aneuploidy in human primary CD4+ T cells. We propose that the Vpr•VprBP•Plk4 complex serves as a molecular link that connects HIV-1 infection to oncogenesis and that inhibiting the Vpr C-terminal motif may reduce the occurrence of HIV-1-associated cancers.


Subject(s)
HIV-1 , T-Lymphocytes , Humans , Centrosome , Carcinogenesis , Cell Transformation, Neoplastic , Aneuploidy , CD4-Positive T-Lymphocytes
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