Mitochondrial dysfunctions in T cells: focus on inflammatory bowel disease

Mitochondria has emerged as a critical ruler of metabolic reprogramming in immune responses and inflammation. In the context of colitogenic T cells and IBD, there has been increasing research interest in the metabolic pathways of glycolysis, pyruvate oxidation, and glutaminolysis. These pathways have been shown to play a crucial role in the metabolic reprogramming of colitogenic T cells, leading to increased inflammatory cytokine production and tissue damage. In addition to metabolic reprogramming, mitochondrial dysfunction has also been implicated in the pathogenesis of IBD. Studies have shown that colitogenic T cells exhibit impaired mitochondrial respiration, elevated levels of mROS, alterations in calcium homeostasis, impaired mitochondrial biogenesis, and aberrant mitochondria-associated membrane formation. Here, we discuss our current knowledge of the metabolic reprogramming and mitochondrial dysfunctions in colitogenic T cells, as well as the potential therapeutic applications for treating IBD with evidence from animal experiments

Nonequilibrium diffusion of active particles bound to a semi-flexible polymer network: simulations and fractional Langevin equation

In a viscoelastic environment, the diffusion of a particle becomes non-Markovian due to the memory effect. An open question is to quantitatively explain how self-propulsion particles with directional memory diffuse in such a medium. Based on simulations and analytic theory, we address this issue with active viscoelastic systems where an active particle is connected with multiple semi-flexible filaments. Our Langevin dynamics simulations show that the active cross-linker displays super- and sub-diffusive athermal motion with a time-dependent anomalous exponent $\alpha$. In such viscoelastic feedback, the active particle always has superdiffusion with $\alpha=3/2$ at times shorter than the self-propulsion time ($\tau_A$). At times greater than $\tau_A$, the subdiffusion emerges with $\alpha$ bounded between $1/2$ and $3/4$. Remarkably, the active subdiffusion is reinforced as the active propulsion (Pe) is more vigorous. In the high-Pe limit, the athermal fluctuation in the stiff filament eventually leads to $\alpha=1/2$, which can be misinterpreted with the thermal Rouse motion in a flexible chain. We demonstrate that the motion of active particles cross-linking a network of semi-flexible filaments can be governed by a fractional Langevin equation combined with fractional Gaussian noise and an Ornstein-Uhlenbeck noise. We analytically derive the velocity autocorrelation function and mean-squared displacement of the model, explaining their scaling relations as well as the prefactors. We find that there exist the threshold Pe ($\mathrm{Pe}^*$) and cross-over times ($\tau^*$ and $\tau^\dagger$) above which the active viscoelastic dynamics emerge on the timescales of $\tau^* \lesssim t \lesssim \tau^\dagger$. Our study may provide a theoretical insight into various nonequilibrium active dynamics in intracellular viscoelastic environments

Theory of magnetic field-induced metaelectric critical end point in BiMn2_2O5_5

A recent experiment on the multiferroic BiMn$_2$O$_5$ compound under a strong applied magnetic field revealed a rich phase diagram driven by the coupling of magnetic and charge (dipolar) degrees of freedom. Based on the exchange-striction mechanism, we propose here a theoretical model with the intent to capture the interplay of the spin and dipolar moments in the presence of a magnetic field in BiMn$_2$O$_5$. Experimentally observed behavior of the dielectric constants, magnetic susceptibility, and the polarization is, for the most part, reproduced by our model. The critical behavior observed near the polarization reversal $(P=0)$ point in the phase diagram is interpreted as arising from the proximity to the critical end point.Comment: Theory; relevant experiment uploaded as arXiv:0810.190

Preoperative Subclinical Hyperthyroidism in Patients With Papillary Thyroid Carcinoma

ObjectivesNumerous studies have reported the effects of subclinical hyperthyroidism on the cardiovascular system, osteoporosis, and metabolic syndrome. However, there are few studies examining the relationships between subclinical hyperthyroidism and thyroid cancer. The aim of this study was to investigate the relationships between preoperative subclinical hyperthyroidism and clinicopathological characteristics in patients with papillary thyroid carcinoma (PTC) in terms of thyroid-stimulating hormone (TSH) levels and TSH receptor antibody (TRAb) values.MethodsBetween January 2001 and December 2007, 462 patients were eligible for analysis in our study; we compared the clinicopathological characteristics of 39 preoperative subclinical hyperthyroidism patients with those of 423 euthyroid patients.ResultsThere were no statistical differences between the 2 groups with respect to age, male to female ratio, primary tumor size, extrathyroidal extension (ETE), multifocality, lymph node metastasis, TNM and AMES stages, recurrence, and survival, despite significant difference in TSH concentrations between the 2 groups. In the evaluation for TRAb, primary tumor size was significantly larger in patients with normal TRAb than in patients with elevated TRAb. When the patients were subdivided into 4 categories according to TRAb values (15.0%), tumor size and ETE were significantly different. However, we could not find linear relationships in the increase or decrease of TRAb values.ConclusionThe results of our study suggest that subclinical hyperthyroidism is not independently associated with tumor aggressiveness and prognosis in PTC in spite of reduced TSH levels and increased TRAb values as compared with euthyroid patients

Effect of Octreotide Injection on Postoperative Drainage After Neck Dissection: A Preliminary Report of a Prospective, Matched Case-Control Study

Objectives Somatostatin inhibits lymph production and reduces lymph flow into the lymphatic duct. We hypothesized that octreotide, a long-acting somatostatin analog, would reduce drainage after neck dissection (ND) by reducing the overall lymphatic flow in the neck as well as thoracic duct flow. Methods From 2012 to 2014, total 123 patients who had undergone left-sided comprehensive ND, were divided into an octreotide group (49 patients) and a control group (74 patients). Seventeen patients from the octreotide group and 17 from the control group were individually matched by age (±10 years), sex, body mass index (±1 kg/m2), type of cancer, surgeon, and the extent of surgery. These 34 patients were finally included in the study. Results The total fluid drainage volume (540.9 mL vs. 707.9 mL) and drainage volume during the period of octreotide use (the first 5 postoperative days) (461.1 mL vs. 676.4 mL) were significantly lower in the octreotide group. The duration of drain placement (6.3 days vs. 9.4 days) was also shorter in the octreotide group. In the octreotide group, the mean triglyceride concentration in the drainage fluid was significantly lower than that in the control group (43.1 mg/dL vs. 88.8 mg/dL). There was no complication associated with the use of octreotide. Conclusion Our study has shown that postoperative octreotide injections reduce postoperative drainage and the duration of drain placement. Further studies with larger patient populations are warranted to confirm these results and to evaluate the clinical benefits for patients

High-fidelity 3D Human Digitization from Single 2K Resolution Images

High-quality 3D human body reconstruction requires high-fidelity and large-scale training data and appropriate network design that effectively exploits the high-resolution input images. To tackle these problems, we propose a simple yet effective 3D human digitization method called 2K2K, which constructs a large-scale 2K human dataset and infers 3D human models from 2K resolution images. The proposed method separately recovers the global shape of a human and its details. The low-resolution depth network predicts the global structure from a low-resolution image, and the part-wise image-to-normal network predicts the details of the 3D human body structure. The high-resolution depth network merges the global 3D shape and the detailed structures to infer the high-resolution front and back side depth maps. Finally, an off-the-shelf mesh generator reconstructs the full 3D human model, which are available at https://github.com/SangHunHan92/2K2K. In addition, we also provide 2,050 3D human models, including texture maps, 3D joints, and SMPL parameters for research purposes. In experiments, we demonstrate competitive performance over the recent works on various datasets.Comment: code page : https://github.com/SangHunHan92/2K2K, Accepted to CVPR 2023 (Highlight

Myositis unrelated to the inoculation site after COVID-19 vaccination: a case report

We describe the case of a 49-year-old right hand-dominant woman with myositis of the biceps brachii muscle unrelated to the inoculation site following Pfizer-BioNTech COVID-19 vaccination on the deltoid muscle of the left shoulder. Coronavirus disease 2019 (COVID-19) pandemic has involved global spread, and different vaccines including inactivated, protein, vectored, and nucleic acid vaccines have been developed and administered. Common side effects of COVID-19 vaccines include general manifestations such as headache, fever, and fatigue, and various musculoskeletal symptoms. Here, we present a case of myositis occurring in the biceps brachii muscle unrelated to the inoculation site, which has not been reported previously, accompanied by a literature review. Level of evidence V

Copy number variation at leptin receptor gene locus associated with metabolic traits and the risk of type 2 diabetes mellitus

<p>Abstract</p> <p>Background</p> <p>Recent efforts have been made to link complex human traits and disease susceptibility to DNA copy numbers. The leptin receptor (LEPR) has been implicated in obesity and diabetes. Mutations and genetic variations of <it>LEPR </it>gene have been discovered in rodents and humans. However, the association of DNA copy number variations at the <it>LEPR </it>gene locus with human complex diseases has not been reported. In an attempt to study DNA copy number variations associated with metabolic traits and type 2 diabetes mellitus (T2DM), we targeted the <it>LEPR </it>gene locus in DNA copy number analyses.</p> <p>Results</p> <p>We identified DNA copy number variations at the <it>LEPR </it>gene locus among a Korean population using genome-wide SNP chip data, and then quantified copy numbers of the E2 DNA sequence in the first two exons overlapped between <it>LEPR </it>and <it>LEPROT </it>genes by the quantitative multiplex PCR of short fluorescent fragment (QMPSF) method. Among the non-diabetic subjects (n = 1,067), lower E2 DNA copy numbers were associated with higher fasting glucose levels in men (<it>p </it>= 1.24 × 10^-7) and women (<it>p </it>= 9.45 × 10^-5), as well as higher total cholesterol levels in men (<it>p </it>= 9.96 × 10^-7). In addition, the significant association between lower E2 DNA copy numbers and lower level of postprandial 2hr insulin was evident only in non-diabetic women, whereas some obesity-related phenotypes and total cholesterol level exhibited significant associations only in non-diabetic men. Logistic regression analysis indicated that lower E2 DNA copy numbers were associated with T2DM (odds ratio, 1.92; 95% CI, 1.26~2.96; p < 0.003) in our nested case-control study. Interestingly, the E2 DNA copy number exhibited a negative correlation with LEPR gene expression, but a positive correlation with LEPROT gene expression.</p> <p>Conclusions</p> <p>This work suggests that a structural variation at the <it>LEPR </it>gene locus is functionally associated with complex metabolic traits and the risk of T2DM.</p

The Link between Mitochondrial Dysfunction and Sarcopenia: An Update Focusing on the Role of Pyruvate Dehydrogenase Kinase 4

Sarcopenia, defined as a progressive loss of muscle mass and function, is typified by mitochondrial dysfunction and loss of mitochondrial resilience. Sarcopenia is associated not only with aging, but also with various metabolic diseases characterized by mitochondrial dyshomeostasis. Pyruvate dehydrogenase kinases (PDKs) are mitochondrial enzymes that inhibit the pyruvate dehydrogenase complex, which controls pyruvate entry into the tricarboxylic acid cycle and the subsequent adenosine triphosphate production required for normal cellular activities. PDK4 is upregulated in mitochondrial dysfunction-related metabolic diseases, especially pathologic muscle conditions associated with enhanced muscle proteolysis and aberrant myogenesis. Increases in PDK4 are associated with perturbation of mitochondria-associated membranes and mitochondrial quality control, which are emerging as a central mechanism in the pathogenesis of metabolic disease-associated muscle atrophy. Here, we review how mitochondrial dysfunction affects sarcopenia, focusing on the role of PDK4 in mitochondrial homeostasis. We discuss the molecular mechanisms underlying the effects of PDK4 on mitochondrial dysfunction in sarcopenia and show that targeting mitochondria could be a therapeutic target for treating sarcopenia