Subcutaneous Fat Tissue Research Articles

Gene Expression of Angiotensin-Converting Enzyme 2 Receptor in Skin and the Implications for COVID-19.

Binding to the angiotensin-converting enzyme 2 (ACE2) receptor is a critical step for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter target cells. This enzyme is expressed in many human tissues including the lungs, but no research has demonstrated that SARS-CoV-2 can infect human skin or subcutaneous fat tissue, despite the increasing number of reported skin manifestations. The aim of this study was to investigate ACE2 gene expression in skin using a public database. A search of transcriptomic data sets from a public gene expression database to investigate ACE2 gene expression in human tissues. Human skin keratinocytes and basal cells express more ACE2 than lung epithelial cells. In contrast, both fibroblasts and melanocytes from human skin express less ACE2 than human lung epithelial cells. The high expression of ACE2 in keratinocytes and basal cells of human skin indicates that they may be directly susceptible to SARS-CoV-2 infection via the ACE2 receptor, especially in conditions of skin barrier dysfunction, and are therefore a potential target for the coronavirus.

SPATA4 improves aging-induced metabolic dysfunction through promotion of preadipocyte differentiation and adipose tissue expansion.

Spermatogenesis‐associated protein 4 (SPATA4) is conserved across multiple species. However, the function of this gene remains largely unknown. In this study, we generated Spata4 transgenic mice to explore tissue‐specific function of SPATA4. Spata4 overexpression mice displayed increased subcutaneous fat tissue compared with wild‐type littermates at an old age, while this difference was not observed in younger mice. Aging‐induced ectopic fat distribution, inflammation, and insulin resistance were also significantly attenuated by SPATA4. In vitro, SPATA4 promoted preadipocyte differentiation through activation of the ERK1/2 and C/EBPβ pathway and increased the expression of adipokines. These data suggest SPATA4 can regulate lipid accumulation in a tissue‐specific manner and improve aging‐induced dysmetabolic syndromes. Clarifying the mechanism of SPATA4 functioning in lipid metabolism might provide novel therapeutic targets for disease interventions.

MiR-32-5p Regulates Lipid Accumulation in Intramuscular Fat of Erhualian Pigs by Suppressing KLF3.

Intramuscular fat (IMF) and subcutaneous fat (SCF) are important traits affecting the economics of the pork industry, in which less SCF and more IMF content is desirable. However, the mechanisms that regulate IMF and SCF content are not clear yet. In this study, we demonstrate that KLF3 (Krüppel-like factor 3) was negatively correlated with IMF content in the longissimus dorsi muscle of Erhualian pigs. In addition, the expression level of KLF3 was significantly higher in IMF than SCF. Overexpression and knockdown experiments revealed that KLF3 could suppress adipocyte differentiation in vitro by downregulating adipogenic markers, including PPARG, C/EBPA, and FABP4. Luciferase activity analysis proved that miR-32-5p was able to suppress KLF3. Notably, miR-32-5p level was negatively correlated to KLF3 mRNA level in both IMF and SCF tissues. The same relationship was proved in samples with different IMF content. Further studies showed that miR-32-5p could promote adipocyte differentiation via inhibiting KLF3. Our results suggest that the miR-32-5p-KLF3 pathway is involved in the regulation of differential fat deposition of IMF and SCF tissues.

Body Mass Index Vs Fracture Risk Value Primary Osteoporosis (A Case Study on Women Ages 40-45 Years at Sub-Urban Area)

This study aims to determine the relationship between BMI and fracture risk value primary osteoporosis in women aged 40-45 years in sub-urban areas. And how to optimize social activities in the environment as an effort to reduce the risk of osteoporosis. Body mass index is one of the important risk factors for osteoporosis fractures because the protective effects of subcutaneous fat tissue on bone in elderly women are calculated using FRAX®tool. The WHO in collaboration with the Sheffield's University central of metabolic bone disease has created a calculating device, the WHO risk assessment fracture tool (FRAX®tool). FRAX®tool is an online-based device used to calculate the risk of osteoporosis fractures in major bones, namely proximal humerus, wrist, vertebrae, and femur bone in the next ten years. This research is an analytical study using a cross sectional design, the number of samples is 70 female respondents aged 40–45 years in Kelurahan Melong Asih, Cimahi. The relationship between body mass index and the risk of primary osteoporosis fracture, used the rank spearman correlation test. The results of this study indicate a strong negative correlation between body mass index and the risk value of osteoporosis major, while the relationship between body mass index and risk value for osteoporosis femur fracture was found to be a moderate negative correlation. From the results of the risk of major osteoporosis fracture the lower a person's body mass index, the greater the risk of major primary osteoporosis fracture, whereas the results of the risk of femur fracture are only in obese grade II that is low, while other criteria have the same value, so it cannot be concluded if the lower a person's body mass index, the greater the risk value of the femur fracture. Keywords : Body Mass Index; Fracture Risk Value; Osteoporosis.

Unraveling molecular mechanisms involved in the development of leptin resistance using the pig as a model.

The increase in obesity worldwide underlines the need for research concerning its metabolic and genetic determinants. One of the most intriguing mechanisms regarding obesity involves leptin and its signaling cascade. Leptin is a key regulator contributing to the fine-tuned crosstalk between nutrient availability and appetite signaling in the central nervous system. Owing to ethical concerns, many human tissues are not readily available and pigs can serve as a good animal model owing to their comparable anatomy, metabolism and genetics. In the present study, we utilized the pig to investigate the possible impact of increased adiposity on the development of alterations within the leptin signaling pathway. Two divergent groups of pigs (High and Low) were defined based on a high and low amount of mesenteric fat. Cortex, cerebellum, hypothalamus, mesenteric, subcutaneous and retroperitoneal fat tissues were used to study changes in expression levels of 94 mRNA transcripts related to the leptin signaling pathway using the qPCR approach. No significant differences were found at the central nervous system, whereas the expression level of STAT1 was reduced in mesenteric fat and leptin (LEP) and interleukin 6 (IL6) were shown to be consistently increased in all analyzed fat compartments from pigs with a high amount of mesenteric fat. These results could imply the onset of leptin and pro-inflammatory cytokine overexpression at early stages of obesity in the analyzed pigs without affecting any key components in the central nervous system. Thus, these pigs showing a unique leptin deregulation in adipose tissues could be a useful translational resource for studies of obesity and leptin resistance phenotypes.

AB015. OP15 Comparison of ultrasound findings and laparoscopic views in the evaluation of hepatosteatosis

Background: Ultrasonographic evaluation of liver may not be clear due to the thickness of subcutaneous fat tissue in morbidly obese patients. In this study, ultrasound findings and laparoscopic views were compared in the evaluation of hepatosteatosis.

Subcutaneous white adipose tissue: The deepest layer of the cutaneous immune barrier.

Mammalian skin, the outer covering of the body, is composed of three layers, i.e. the epidermis, the dermis and the subcutaneous white adipose tissue (SWAT). While the contribution of epidermis and dermis to the skin's immune function is well established, the role, if any, of SWAT in this regard has yet to be determined. Human SWAT is made up of lobules which consist mainly of adipocytes and are subdivided and separated from each other by vascularized septae of connective tissue. An immunophenotypic analysis of liposuction-derived SWAT demonstrated that healthy subcutaneous fat tissue, although showing no overt signs of inflammation, harbors an indigenous system of immunocytes. As opposed to epidermis and dermis, they belong mainly to the mononuclear phagocyte lineage and, to a lesser extent, represent T-lymphocytes. Their phenotype indicates that these two major subsets of SWAT leukocytes are primarily concerned with ant-inflammatory and/or regulatory functions. It thus appears that SWAT is more than a cushion protecting against mechanical trauma, and may subserve immunomodulatory functions aimed at preventing or, at least, mitigating exaggerated immune and/or inflammatory reactions..

Myostatin regulates fatty acid desaturation and fat deposition through MEF2C/miR222/SCD5 cascade in pigs

Myostatin (MSTN), associated with the “double muscling” phenotype, affects muscle growth and fat deposition in animals, whereas how MSTN affects adipogenesis remains to be discovered. Here we show that MSTN can act through the MEF2C/miR222/SCD5 cascade to regulate fatty acid metabolism. We generated MSTN-knockout (KO) cloned Meishan pigs, which exhibits typical double muscling trait. We then sequenced transcriptome of subcutaneous fat tissues of wild-type (WT) and MSTN-KO pigs, and intersected the differentially expressed mRNAs and miRNAs to predict that stearoyl-CoA desaturase 5 (SCD5) is targeted by miR222. Transcription factor binding prediction showed that myogenic transcription factor 2C (MEF2C) potentially binds to the miR222 promoter. We hypothesized that MSTN-KO upregulates MEF2C and consequently increases the miR222 expression, which in turn targets SCD5 to suppress its translation. Biochemical, molecular and cellular experiments verified the existence of the cascade. This novel molecular pathway sheds light on new targets for genetic improvements in pigs.

Quantification of microdialysis related variability in humans: Clinical trial design recommendations

ObjectiveTarget-site concentrations obtained via the catheter-based minimally invasive microdialysis technique often exhibit high variability. Catheter calibration is commonly performed via retrodialysis, in which a transformation factor, termed relative recovery (RR), is determined. Leveraging RR values from a rich data set of a very large clinical microdialysis study, promised to contribute critical insight into the origin of the reportedly high target-site variability. The present work aimed (i) to quantify and explain variability in RR associated with the patient (including non-obese vs. obese) and the catheter, and (ii) to derive recommendations on the design of future clinical microdialysis studies. MethodsA prospective, age- and sex-matched parallel group, single-centre trial in non-obese and obese patients (BMI=18.7-86.9 kg/m2) was performed. 1-3 RR values were obtained in the interstitial fluid of the subcutaneous fat tissue in one catheter per upper arm of 120 patients via the retrodialysis method (nRR=1008) for a panel of drugs (linezolid, meropenem, tigecycline, cefazolin, fosfomycin, piperacillin and acetaminophen). A linear mixed-effects model was developed to quantify the different types of variability in RR and to explore the association between RR and patient body size descriptors. ResultsEstimated RR was highest for acetaminophen (69.7%, 95%CI=65.0% to 74.3%) and lowest for piperacillin (40.4%, 95%CI=34.6% to 46.0%). The linear mixed-effects modelling analysis showed that variability associated with the patient (σ=15.9%) was the largest contributor (46.7%) to overall variability, whereas the contribution of variability linked to the catheter (σ=5.55%) was ~1/6 (16.8%). The relative contribution of residual unexplained variability (σ=12.0%, including intracatheter variability) was ~1/3 (36.4%). The limits of agreement of repeated RR determinations in a single catheter ranged from 0.694-1.64-fold (linezolid) to 0.510-3.02-fold (cefazolin). Calculated fat mass affected RR, explaining the observed lower RR in obese (ΔRRmean= -29.7% relative reduction) versus non-obese patients (p<0.001); yet only 15.8% of interindividual variability was explained by this effect. No difference in RR was found between catheters implanted into the left or right arm (p=0.732). ConclusionsThree recommendations for clinical microdialysis trial design were derived: 1) High interindividual variability underscored the necessity of measuring individual RR per patient. 2) The low relative contribution of intercatheter variability to overall variability indicated that measuring RR with a single catheter per patient is sufficient for reliable catheter calibration. 3) The wide limits of agreement from multiple RR in the same catheter implied an uncertainty of a factor of two in target-site drug concentration estimation necessitating to perform catheter calibration (retrodialysis sampling) multiple times per patient. To allow routine clinical use of microdialysis, research efforts should aim at further understanding and minimising the method-related variability. Optimised study designs in clinical trials will ultimately yield more informative microdialysis data and increase our understanding of this valuable sampling technique to derive target-site drug exposure.

Cutaneous ulcer resembling pyoderma gangrenosum in a patient with antiphospholipid syndrome

The present case presented with abrupt appearance of rapidly enlarging ulcerations over his legs that resembled PG with no atypical histopathological findings such as dermal infiltrate showing numerous neutrophils. The pathogenesis of PG-like cutaneous ulcer in the present case could be related to some abnormalities in the coagulation/fibrinolysis pathways and an abnormal immune condition that involves antiphospholipid antibodies. Cutaneous manifestations of antiphospholipid syndrome (APS) vary from livedo reticularis to cutaneous necrosis, with the appearance of associate cutaneous ulcers with sharp margins, typically over the legs.1 Classic pyoderma gangrenosum (PG), also known as ulcerative type, is characterized by rapidly progressive ulcers with violaceous indurated borders. The diagnosis remains challenging due to the lack of a gold standard diagnostic test.2 A 39-year-old man presented with a reddish necrotic and erosive lesion and cutaneous ulcers all over his legs that had appeared one month earlier. Physical examination revealed various sized necrotic ulcers include papules, vesicles, and pustules over both his legs, along with dense brown pigmentation (Figure 1A). Microscopic findings showed dermal fibrosis, intravascular hyalinized material of fibrin-containing thrombi with cell inflammation and capillary dilatation in the upper to middle dermis (Figure 1B). Antibiotic treatment alone was insufficient, and the lesion continued to gradually increase in size. He had abrupt appearance of rapidly enlarging and hemorrhagic ulcerations on his right leg. Cutaneous ulcers in the lateral femoral region of the right leg were found with undermined, overhanging, dusky purple edges, and surrounding induration and erythema (Figure 1C). Histopathological examination revealed a severe dermal infiltrate comprised of neutrophils and lymphocytic cells and capillary dilatation and thrombi in the dermis to subcutaneous fat tissue (Figure 1D). The clinical features of the cutaneous ulcer suggested a diagnosis of PG. In contrast, histopathological findings showed thrombi and vascular damage in the dermal capillary vessels with neutrophilic infiltrate. Laboratory examinations showed increased anti-cardiolipin antibodies (112 U/mL; normal range, <9 U/mL) and anti-β2 glycoprotein I antibodies (>125 U/mL; normal range 0-3.4 U/mL), and the lupus anticoagulant was detected. Abdominal contrast-enhanced computed tomography revealed thrombi, contraction, and occlusion of the abdominal aorta and iliac arteries (Figure 1E). Ultrasonography of his veins showed thrombi in the femoral veins, popliteal veins, and flounder veins. Based on these findings, he was diagnosed with APS. He responded to anticoagulation treatment with warfarin alone and his cutaneous ulcer that had initially been diagnosed as PG improved. Classic ulcerative PG is characterized by a peripheral erythematous inflammatory halo and the edges are erythematous, raised, and sometimes necrotic, with an undermining border, the size of which determines how rapidly the ulcer edge will evolve.2, 3 The present case presented with abrupt appearance of rapidly enlarging ulcerations over his legs that resembled PG with no atypical histopathological findings such as dermal infiltrate showing numerous neutrophils. There have been other reports of PG-like ulcers in patients with APS.3, 4 Recent studies have also suggested that lupus anticoagulant and anti-cardiolipin antibodies could be an important risk factor for venous ulcers of the leg.5 These antiphospholipid antibodies potentially cause repeated thrombi which lead to chronic damage of the skin and eventually to poorly healing venous ulcers over the long term. We propose that the pathogenesis of PG-like cutaneous ulcer in the present case could be related to some abnormalities in the coagulation/fibrinolysis pathways and an abnormal immune condition that involves antiphospholipid antibodies. The authors declares no conflict of interest. Approval of the research protocol and Informed Consent were performed by Tohoku Medical and Pharmaceutical University, Sendai, Japan. Registry and the Registration No. of the study/trial: N/A. Animal Studies: N/A

The Influence of the Demographic Factor on the Growth and Development of Younger School-Age Girls

In order to determine the difference in morphological characteristics, a survey was conducted on a sample of 120 fourth-grade elementary schoolgirls from different socio-economic backgrounds in Montenegro. The total sample of respondentswas divided into two sub-samples. One sub-group consisted of 60 schoolgirls from urban and the other 60 schoolgirls of the same age from rural environment. A sample of measuring instruments consisted of 12 measures (body height, arm length, leg length, shoulder width, elbow diameter, knee diameter, body mass, upper arm circumference, lower leg circumference, skin fold of the back, skin fold of the upper arm and skin fold of the abdomen). In the process of statistical data processing, descriptiveand canonical discriminatory analysis were applied in order to identify possible differences between sub-databases. The obtained research data generally indicate the existence of statistically significant differences between sub-samples. This difference is evident in indicators of longitudinal and transversal dimensionality of the skeleton, and in contrast, the difference was not evident in indicators of volume and body weight and subcutaneous fat tissue. Girls from the urban environment were taller and had more pronounced measures in the upper and lower extremities and girls from rural areas had more pronounced measures of knee joint diameter than their peers from urban life.

Elevated adipose tissue associated IL-2 expression in obesity correlates with metabolic inflammation and insulin resistance

Adipose tissue (AT) associated cytokines are involved in the development of chronic low-grade inflammation in obese individuals. IL-2, a pleiotropic cytokine, contributes to immune alterations during inflammation. However, the interaction between AT-IL-2 and other inflammatory biomolecules in obesity remains elusive. We investigated whether AT-IL-2 expression was associated with markers of inflammation and insulin resistance in overweight/obese individuals. Subcutaneous fat tissues were collected from 56 individuals (lean/overweight/obese) for RNA extraction. IL-2 and inflammatory mediators were quantified by qRT-PCR and immunohistochemistry. CRP was measured by ELISA. AT-IL-2 expression was higher in obese compared with lean individuals (P < 0.021) and correlated with BMI. IL-2 correlated with interleukins IL-8 and IL-12A (r = 0.333–0.481; p = 0.0001–0.029); as well as with chemokines and their receptors including CCL5, CCL19, CCR2 and CCR5 (r = 0.538–0.677; p < 0.0001). Moreover, IL-2 correlated with toll-like receptors (TLR2, TLR8, TLR10), interferon regulatory factor 5 (IRF5) and cluster of differentiation CD11c (r = 0.282–0.357; p < 0.039). Notably, IL-2 was associated positively with fasting blood glucose (FBG), HbA1c, TGL and CRP (r ≥ 0.423;P ≤ 0.007). In multiple regression analysis, IL-2 is an independent predictor of IL-8, IL-12A, TLR10, TGL and HbA1c. Overall, our data demonstrate that increased expression of the AT-IL-2, in obesity, may represent a novel biomarker for progression of metabolic inflammation and insulin-resistance.

Micro-Autologous Fat Transplantation (MAFT) for Dorsal Hand Rejuvenation

Introduction: The dorsal surfaces of our hands are highlyvisible parts of the body. However with ageing, the aestheticaspects of the hand deteriorate both in skin quality and contourwith obvious appearance of dorsal blue veins and extensortendons and loss or absence of subcutaneous fat tissue. Theliterature reports multiple options for addressing this problem,yet, all of these choices come with their own complications.Micro-autologous fat transplantation (MAFT) can be used inhand rejuvenation by a combined effect. First, it is possibleto augment the dorsum of the hand and enabling visible blueand tortious veins as well as extensor tendons to be covered,resulting in a hand with uniform contour. Second, the fat cellshave a beneficial effect on deep and superficial skin tissuevia adipocytes derived stem cells (ASCs), thereby rejuvenatingthe hand. In this study, we performed (MAFT) technique tothe three dorsal subcutaneous laminae for the rejuvenation ofdorsal hand surfaces and determined its clinical results.Patients and Methods: MAFT was performed in 10 femalepatients. Fat was harvested by performing liposuction fromdifferent body sites, then processed, and refined by decantation.Purified fat was micro-transplanted to the dorsal surface ofthe hand in parcels of small volume. Post treatment checkupswere performed at 24h, 7 days, 1 month, 3 months, and6 months after treatment to evaluate the healing cascade ofthe hand. Patient-rated satisfaction was reported during thepatient's final visit (at least 6 months after MAFT) using a 5-point scale. The Merz Hand Grading Scale (MHGS) was usedto grade the appearance of the dorsal hand preoperatively and6 months after MAFT.Results: The mean age was 46 years (range, 36-60 years).The time taken for MAFT injection of both hands was in anaverage of 30min. On average, the fat volume delivered was20 and 18.5mL for the right and left hands, respectively. Nomajor complications were reported, only mild to moderateswelling was noted, which subsided after 7 to 10 days postoperatively.Favorable outcomes were noted in patients whichwas reflected on the patient satisfaction rate (very satisfied,60% and satisfied, 30%) and the remarkable up grading inthe Merz Hand Grading Scale.Conclusion: In conclusion, the clinical results obtainedusing MAFT have demonstrated the feasibility and effectivenessof this approach in creating a younger and more beautifuldorsal hand appearance. However, longer studies in a largerpatient population are required to assess long-term outcomes.

Energy Consumption of Young Military Working Dogs in Pre-Training in Germany.

Simple SummaryAppropriate energy supply adjusted to the requirements of military working dogs at pre-training is a basic prerequisite for working dogs, so they are fully able to exercise. Therefore, twenty Belgian Shepherds var. Malinois were accompanied for four weeks during pre-training as military working dogs, and the amount of energy intake was evaluated. Changes in body constitution were assessed by measuring body weight and shoulder height, as well as thickness of subcutaneous fat tissue, and of Musculus sacrocaudalis dorsalis lateralis (MSCDL). Energy intake amounted to, on average, 244 kcal/kg body weight (BW)0.75 daily. Changes to body constitution (increases in body weight, shoulder height, and thickness of the MSCDL, as well as a reduction of the thickness of the subcutaneous fat tissue lying on the MSCDL) might be attributed to training-induced muscle growth and physiological growth in size. In addition to training intensity, influences of ambient temperature and physiological body growth seemed to be important contributing factors in the supply of energy for military working dogs (MWDs) during pre-training.Many factors have specific effects, in varying degrees of intensity, on the metabolic energy requirements of working dogs. Appropriate energy supply adjusted to the requirements of military working dogs at pre-training is a basic prerequisite for working dogs, so they are fully able to exercise. Therefore, more knowledge obtained under standardized conditions would be advantageous. Twenty intact Belgian Shepherds var. Malinois at the age of 12 months were accompanied for four weeks during pre-training (odour detection, obedience training, and protection work) as military working dogs (MWDs) in Germany (ambient temperature about 7.8 °C), and the amount of energy intake was evaluated. To assess changes in body constitution, body weight and shoulder height were measured, and the thickness of subcutaneous fat tissue (SCF), and of Musculus sacrocaudalis dorsalis lateralis (MSCDL), were recorded via ultrasound. Energy intake amounted to, on average, 244 ± 34 kcal/kg body weight (BW)0.75 daily. Increases in body weight, shoulder height, and thickness of the MSCDL, as well as a reduction of SCF thickness lying on the MSCDL, were observed. Changes of body constitution might be attributed to training-induced muscle growth and physiological growth in size. In addition to training intensity, influences of ambient temperature and physiological body growth seemed to be important contributing factors in the supply of energy for MWDs during pre-training.

A report of a case: unusual portosystemic shunt in a hernia sac who has portal hypertension due to cirrhosis

Variations in the origin and branching pattern of splenic vein (SV) are relatively rare and asymptomatic. We describe here only the first case in the literature of accessory SV in hernia sac due to previous operation and increased portal pressure because of cirrhosis. This report describes a 66-year-old female, with a history of total abdominal hysterectomy (TAH) due to uterine myomatosis, signs of cirrhosis onset due to hepatitis B, who had been presented with recurrent abdominal pain attacks. Ultrasonography (USG) findings were nothing pathologic except a gallstone in the gallbladder without cholecystitis signs. Incisional hernia was found to contain an accessory SV in the hernia sac arising from a branch of main SV in the hilum, ongoing to the subcutaneous fat tissue and draining to the superficial femoral vein on computed tomography (CT). Videoendoscopy showed wide gastritis and multiple ulcers. The patient's symptoms diminished with proton pump inhibitor (PPI) treatment and they then underwent a hernia repair surgery with Prolene mesh patch as elective surgery. A thorough knowledge of the normal anatomy, most frequent variations and congenital or acquired anomalies of the spleno-portal axis has great importance for hepatopancreaticobiliary and emergency surgical procedures. It is, therefore, essential for preoperative evaluation of the anatomical details of the spleno-portal venous axis and should be evaluated with imaging methods in detail.

Characteristics of the liver parenchyma according to the native CT examinations data at the stages of COVID-19 treatment

Purpose . To assess the liver density according to the data of native CT studies in patients with COVID-19, depending on the severity of the pulmonary parenchyma damage and the prescribed treatment, to compare the data with biochemical indicators, and also to demonstrate changes in density indicators over time. Material and methods . Lung CT data from 200 patients with COVID-19 were retrospectively analyzed. The density of the liver, spleen, and subcutaneous fat tissue was measured in all patients on the images of the upper abdominal cavity that entered the scan area. The ratio of the density of the liver to the spleen and to the density of the fat tissue was assesed. These indicators were compared with each other in two groups of lung tissue damage: CT 1—2 and CT 3—4. The CT 3—4 group was assessed in detail: the density indicators of the liver were studied in dynamics, and their relationship with biochemical indicators — during the initial study. A comparison was also made between two subgroups: patients taking tocilizumab and those without tocilizumab. Results . A decrease in liver density and the ratio of liver density to spleen density was observed in 35.5% and 47.5% of patients respectively. Liver density and the ratio of liver density to spleen density were lower in the CT 3—4 group than in the CT 1—2 group, and amounted to 43.9 HU versus 49.3 HU ( p &lt; 0.008) and 0.9 versus 1.0 respectively ( p &lt; 0.014). In the initial study, there were a moderate ( r = -0.30; p &lt; 0.05) and weak ( r = -0.26; p &lt; 0.05) negative correlation of liver density and the ratio of liver density to spleen density with serum albumin. When assessing the dynamics in patients in the CT 3—4 group, with each subsequent study, an increase in the density of the liver parenchyma and the ratio of liver density to spleen density was noted. The difference between the mean values of liver density at the first and at the fourth CT examinations was 11.85 HU. Liver density values were independent of treatment with tocilizumab. Conclusion . Liver density values were lower in patients with COVID-19 with the degree of lung parenchyma lesion CT 3—4, increased during treatment and did not depend on the prescription of tocilizumab. Evaluation and monitoring of the dynamics of liver density could become a useful parameter in determining the severity of the disease course. No strong relationships were found between the density parameters during primary CT and any of the biochemical parameters. A more detailed analysis of these changes in dynamics is required, which may suggest the prevailing mechanism of liver damage in COVID-19.

Effect of 8-Week Endurance Training on the Content of Mtor and SREBP1 Proteins in Subcutaneous Fat Tissue in Obese Type 2 Diabetic Male Sprague-Dawley Rats

Introduction: The mTOR and SREBP1 proteins play an important role important in the regulation and metabolism of adipose tissue that can be activated through the mTORC1 pathway. The purpose of the present study was to investigate the effect of 8 weeks endurance training on the content of mTOR and SREBP1 proteins in subcutaneous fat tissue in obese type 2 diabetic male Sprague-Dawley rats. Methods: In this experimental study, 16 three-month-old Sprague-Dawley rats with a mean weight of 300±20 g were selected. After diabetic induction with Streptozotocin and Nicotinamide, rats were randomly assigned to two groups, diabetic training (n=8) and diabetic control (n=8). The training group trained for 4 days a week in accordance with the training program for 8 weeks, while the control group did not have any training program. The independent t-test in SPSS software ver. 19 was used to analyze the data. Results: There was a significant increase in the content of mTOR (p&lt;0.0001) and SREBP1 (p&lt;0.0001) proteins in the training group compared to control; The control group weight increased (p&lt;0.003) and training group (p&lt;0.002) significantly decreased at the end of the eighth week compared to the first week. The blood glucose increased in the control group (p&lt;0.001) and decreased in the exercise group (p&lt;0.0001) in the eighth week compared to the first week. Conclusion: Endurance training can adjust the weight, blood glucose and proteins content of mTOR and SREBP1; Therefore, endurance training can be an important factor in controlling and regulating fat tissue metabolism; this type of training can be effective for obese subjects with type 2 diabetes.

KMT5c modulates adipocyte thermogenesis by regulating Trp53 expression

Brown and beige adipocytes harbor the thermogenic capacity to adapt to environmental thermal or nutritional changes. Histone methylation is an essential epigenetic modification involved in the modulation of nonshivering thermogenesis in adipocytes. Here, we describe a molecular network leading by KMT5c, a H4K20 methyltransferase, that regulates adipocyte thermogenesis and systemic energy expenditure. The expression of Kmt5c is dramatically induced by a β3-adrenergic signaling cascade in both brown and beige fat cells. Depleting Kmt5c in adipocytes in vivo leads to a decreased expression of thermogenic genes in both brown and subcutaneous (s.c.) fat tissues. These mice are prone to high-fat-diet-induced obesity and develop glucose intolerance. Enhanced transformation related protein 53 (Trp53) expression in Kmt5c knockout (KO) mice, that is due to the decreased repressive mark H4K20me3 on its proximal promoter, is responsible for the metabolic phenotypes. Together, these findings reveal the physiological role for KMT5c-mediated H4K20 methylation in the maintenance and activation of the thermogenic program in adipocytes.

Lipoatrophy in children, adolescents and adults with insulin pump treatment: Is there a beneficial effect of insulin glulisine?

To investigate whether zinc-free insulin is an effective treatment option for lipoatrophy. Controlled, randomized, open-label parallel study in young people with type 1 diabetes, pump treatment and lipoatrophy at injection sites. Participants underwent dermatological examination and evaluation of affected areas using ultrasound and magnetic resonance imaging (MRI). After randomization, half of themswitched to insulin glulisine (intervention group) for 6 months. The control group continued their treatment with zinc-containing insulin and switched to insulin glulisine 6 months later. Both groups were followed-up until month 12. Primary endpoint was the increase of the relative thickness of the subcutaneous fat layer of the most atrophic site at 6 months as documented by MRI. Fourteen participants were included into the study. While relative thickness of subcutaneous fat tissue was comparable between intervention (-60% [-98.8 - -17.6], n = 7) and control group (-50% [-72.7 - -1.0], P = .511; median (range), n = 7)at baseline, it improved in the intervention (-14.3% [-85.7-83.3] vs -31.3% (-66.7-0), P = .031), but not in the control group (P = .125) after 6 months. At 12 months, relative fat thickness (P = .003), number (P = .015) and size of most atrophic sites (P = .001) were improved in the intervention group. Number (P = .018) and size of most atrophic sites (P = .008) were also reduced in the control group between 6 and 12 months. Although the present pilot study is based on a small sample, the data give first hint that the use of the zinc-free insulin glulisine may be beneficial in people with diabetes, pump and lipoatrophy.

Development of an invasive ductal carcinoma in a contralateral composite nipple graft after an autologous breast reconstruction: a case report

BackgroundNipple-areola complex (NAC) reconstruction is a technique used in breast reconstructive surgery, which is performed during the final stage of breast reconstruction after total mastectomy of primary breast cancer. Composite nipple grafts utilizing the contralateral NAC are common; however, to our knowledge, there are no reports of new primary invasive ductal carcinoma development within the graft. Here, we describe one such case for the first time.Case presentationA 54-year-old woman was referred to us by the Department of Plastic and Reconstructive Surgery in our medical center for further evaluation of right nipple erosion. She had undergone total mastectomy of the right breast following a breast cancer diagnosis 15 years ago, at which time tumor biological profiling revealed the following: estrogen receptor (ER), positive; progesterone receptor (PgR), negative; and human epidermal growth factor receptor 2 (HER2), undetermined. She received adjuvant chemotherapy and endocrine therapy. She defaulted endocrine therapy for a few years, and 7 years after surgery, she underwent autologous breast reconstruction with a deep inferior epigastric perforator (DIEP) flap. In the following year, NAC reconstruction was performed using a composite graft technique. Seven years after the NAC reconstruction, erosion appeared on the nipple grafted from its contralateral counterpart; scrape cytology revealed malignancy. The skin on the right side of her chest around the NAC and subcutaneous fat tissue consisted of transferred tissue from the abdomen, as the DIEP flap and grafted nipple were located on the graft skin. The right nipple carcinoma arose from the tissue taken from the left nipple. Magnetic resonance imaging (MRI) or computed tomography showed no malignant findings in the left breast. As the malignant lesion seemed limited to the area around the grafted right nipple on MRI, surgical resection with sufficient lateral and deep margins was performed around the right nipple. Pathological findings revealed invasive ductal carcinoma with comedo ductal components infiltrating the graft skin and underlying adipose tissue. Immunohistochemistry revealed positive for ER, PgR, and HER2.ConclusionsTo our knowledge, this is the first case involving the development of invasive ductal carcinoma in a nipple graft constructed on the skin of a DIEP flap, with the origin from the contralateral breast’s nipple.