The annual Breath Biopsy Conference hosted by Owlstone Medical gathers together the leading experts, early career researchers, and physicians working with breath as a biomarker platform for clinical purposes. The current topics in breath research are discussed and presented, and an overarching topical theme is identified and discussed as part of an expert panel to close the conference. The profiling of normal breath composition and the establishment of standards for analyzing breath compared to background signal were two important topics that were major focuses of this conference, as well as important innovative progress that has been made since last year, including the development of a non-invasive breath test for lung cancer and liver disease. This meeting report offers an overview of the key take-home messages from the various presentations, posters, and discussions from the conference.
Biomarkers , Breath Tests , Humans , Breath Tests/methods , Biomarkers/analysis , Biopsy , Congresses as Topic , Lung Neoplasms/diagnosis
Long noncoding RNAs (lncRNAs) are a newer class of noncoding transcripts identified as key regulators of biological processes. Here we aimed to identify novel lncRNA targets that play critical roles in major human respiratory viral infections by systematically mining large-scale transcriptomic datasets. Using bulk RNA-sequencing (RNA-seq) analysis, we identified a previously uncharacterized lncRNA, named virus inducible lncRNA modulator of interferon response (VILMIR), that was consistently upregulated after in vitro influenza infection across multiple human epithelial cell lines and influenza A virus subtypes. VILMIR was also upregulated after SARS-CoV-2 and RSV infections in vitro. We experimentally confirmed the response of VILMIR to influenza infection and interferon-beta (IFN-ß) treatment in the A549 human epithelial cell line and found the expression of VILMIR was robustly induced by IFN-ß treatment in a dose and time-specific manner. Single cell RNA-seq analysis of bronchoalveolar lavage fluid (BALF) samples from COVID-19 patients uncovered that VILMIR was upregulated across various cell types including at least five immune cells. The upregulation of VILMIR in immune cells was further confirmed in the human T cell and monocyte cell lines, SUP-T1 and THP-1, after IFN-ß treatment. Finally, we found that knockdown of VILMIR expression reduced the magnitude of host transcriptional responses to IFN-ß treatment in A549 cells. Together, our results show that VILMIR is a novel interferon-stimulated gene (ISG) that regulates the host interferon response and may be a potential therapeutic target for human respiratory viral infections upon further mechanistic investigation.
BACKGROUND: Surgery is the recommended treatment for breast cancer, the most common cancer in women in Taiwan and the leading cause of cancer-related deaths. Although breast-conserving surgery (BCS) has good prognosis, in some cases, BCS may cause more significant deformities and interfere with the patient's psychosocial well-being. Oncoplastic breast surgery (OBS) is the treatment option in these cases. This study aimed to determine the outcomes of OBS and BCS regardless of clinical and patient-reported esthetic outcomes. METHODS: Between 2015 and 2020, 50 patients who underwent OBS at our hospital after complete treatment were enrolled. With 1:2 matched ratios, 100 patients were enrolled in the BCS control group. Clinical outcomes were analyzed. The BREAST-Q questionnaire was then assessed 6 months after the completion of treatment for subjective patient-reported outcomes. RESULTS: Due to the matching process, no difference was noted between the two groups in terms of demographic data such as age, comorbidities, or tumor characteristics. There were no significant differences in the local recurrence rate, disease-free survival, overall survival, positive margin rate, rewide excision rate, conversion to mastectomy rate, or complication rate (major or minor) between both groups. However, the OBS group showed higher satisfaction with breasts in the BREAST-Q questionnaire ( p < 0.001). The mean follow-up time was 38.77 ± 14.70 months in the BCS group and 29.59 ± 14.06 months in the OBS group. CONCLUSION: OBS seems to be a safe and feasible surgery in breast cancer patients because clinical outcomes are compatible with BCS. Moreover, the OBS group had better patient-reported outcomes in terms of satisfaction.
Breast Neoplasms , Mammaplasty , Humans , Female , Mastectomy , Breast Neoplasms/pathology , Cohort Studies , Mastectomy, Segmental/adverse effects , Patient Reported Outcome Measures , Retrospective Studies
Exhaustive exercise can induce unique physiological responses in the lungs and other parts of the human body. The volatile organic compounds (VOCs) in exhaled breath are ideal for studying the effects of exhaustive exercise on the lungs due to the proximity of the breath matrix to the respiratory tract. As breath VOCs can originate from the bloodstream, changes in abundance should also indicate broader physiological effects of exhaustive exercise on the body. Currently, there is limited published data on the effects of exhaustive exercise on breath VOCs. Breath has great potential for biomarker analysis as it can be collected non-invasively, and capture real-time metabolic changes to better understand the effects of exhaustive exercise. In this study, we collected breath samples from a small group of elite runners participating in the 2019 Ultra-Trail du Mont Blanc ultra-marathon. The final analysis included matched paired samples collected before and after the race from 24 subjects. All 48 samples were analyzed using the Breath Biopsy Platform with GC-Orbitrap™ via thermal desorption gas chromatography-mass spectrometry. The Wilcoxon signed-rank test was used to determine whether VOC abundances differed between pre- and post-race breath samples (adjustedP-value < .05). We identified a total of 793 VOCs in the breath samples of elite runners. Of these, 63 showed significant differences between pre- and post-race samples after correction for multiple testing (12 decreased, 51 increased). The specific VOCs identified suggest the involvement of fatty acid oxidation, inflammation, and possible altered gut microbiome activity in response to exhaustive exercise. This study demonstrates significant changes in VOC abundance resulting from exhaustive exercise. Further investigation of VOC changes along with other physiological measurements can help improve our understanding of the effect of exhaustive exercise on the body and subsequent differences in VOCs in exhaled breath.
Body Fluids , Volatile Organic Compounds , Humans , Breath Tests/methods , Volatile Organic Compounds/analysis , Exhalation , Gas Chromatography-Mass Spectrometry/methods , Body Fluids/chemistry
Although obese sarcopenia is a major public health problem with increasing prevalence worldwide, the factors that contribute to the development of obese sarcopenia are still obscure. In order to clarify this issue, a high-fat-diet-induced obese sarcopenia mouse model was utilized. After being fed with a high-fat diet for 24 weeks, decreased motor functions and muscle mass ratios were found in the C57BL/6 mice. In addition, the expression of calsarcin-2 was significantly increased in their skeletal muscle, which was determined by a microarray analysis. In order to clarify the role of calsarcin-2 in muscle, lentiviral vectors containing the calsarcin-2 gene or short hairpin RNA targeted to calsarcin-2 were used to manipulate calsarcin-2 expressions in L6 myoblasts. We found that an overexpression of calsarcin-2 facilitated L6 myoblast differentiation, whereas a calsarcin-2 knockdown delayed myoblast differentiation, as determined by the expression of myogenin. However, the calsarcin-2 knockdown showed no significant effects on myoblast proliferation. In addition, to clarify the relationship between serum calsarcin-2 and sarcopenia, the bilateral gastrocnemius muscle mass per body weight in mice and appendicular skeletal muscle mass index in humans were measured. Although calsarcin-2 facilitated myoblast differentiation, the serum calsarcin-2 concentration was negatively related to skeletal muscle mass index in mice and human subjects. Taken together, calsarcin-2 might facilitate myoblast differentiation and appear to play a compensatory role in sarcopenia.
Due to the change in the structure of the proximal femur and acetabulum in patients with developmental dysplasia of the hip, total hip arthroplasty (THA) was difficult to perform for surgeons. To elevate the acetabular coverage rate, we developed a technique in the use of a patient-specific instrumentation (PSI) graft in patients with developmental dysplasia of hip (DDH) undergoing surgery. This study aims to evaluate the peri-operative outcomes of THA with PSI graft in patients with DDH. This study recruited 6 patients suffering from Crowe I DDH with secondary Grade IV osteoarthritis. All the patients underwent THA with PSI graft performed by a well-experienced surgeon. Perioperative outcomes included surgical procedures, blood loss during operation, the volume of blood transfusion, length of hospitalization, complications, and the mean difference in hemoglobin levels before and after surgery. All the outcomes analyzed were assessed by mean and standard deviation. The average duration of the surgical procedure was found to be 221.17 min, with an SD of 19.65 min. The mean blood loss during the operation was 733.33 mL, with an SD of 355.90 mL. The mean length of hospital stay was calculated to be 6 days, with an SD of 0.89 days. Furthermore, the mean difference between the pre- and postoperative hemoglobin levels was 2.15, with an SD of 0.99. A total of three patients received 2 units of leukocyte-poor red blood cells (LPR) as an accepted blood transfusion. There were no reported complications observed during the admission and one month after the operation. This study reported the peri-operative outcomes in the patients with DDH who underwent THA with PSI graft. We found that THA with PSI graft would provide a safe procedure without significant complications. We assumed that the PSI graft in THA may increase the coverage rate of the acetabulum, which may increase the graft union rates. Further cohort studies and randomized controlled trials were needed to confirm our findings.
BACKGROUND: The management of knee osteoarthritis involves various treatment strategies. It is important to explore alternative therapies that are both safe and effective. Collagen peptides have emerged as a potential intervention for knee osteoarthritis. This study aims to evaluate the analgesic effects and safety of collagen peptide in patients diagnosed with knee osteoarthritis. METHODS: We conducted a systematic literature search following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Multiple databases including PubMed, Scopus, EMBASE, Web of Science, Cochrane, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) published up to 27 May 2023 that focused on the analgesic outcomes and adverse events associated with collagen peptides or hydrolyzed collagen in patients with osteoarthritis. We assessed the quality of the included studies and the strength of evidence using the Cochrane ROB 2.0 tool and Grading of Recommendations, Assessment, Development, and Evaluations. RESULTS: Four trials involving 507 patients with knee osteoarthritis were included and analyzed using the random-effects model. All these trials were considered to have a high risk of bias. Our results revealed a significant difference in pain relief between the collagen peptide group and the placebo group in patients with knee osteoarthritis (standardized mean difference: - 0.58; 95% CI - 0.98, - 0.18, p = 0.004; I2: 68%; quality of evidence: moderate). However, there was no significant difference in the risk of adverse events between collagen peptide and placebo (odds ratio: 1.66; 95% CI 0.99, 2.78, p = 0.05; I2: 0%; quality of evidence: very low). CONCLUSIONS: Our findings demonstrate significant pain relief in patients with knee osteoarthritis who received collagen peptides compared to those who received placebo. In addition, the risk of adverse events did not differ significantly between the collagen peptide group and the placebo group. However, due to potential biases and limitations, well-designed randomized controlled trials are needed to validate and confirm these findings.
Osteoarthritis, Knee , Humans , Osteoarthritis, Knee/drug therapy , Randomized Controlled Trials as Topic , Analgesics , Collagen/therapeutic use , Peptides , Pain
Hepatic dysfunction is commonly observed in subjects with hyperthyroidism. Hepassocin is a hepatokine playing an important role in metabolic diseases and exhibiting a hepatic protective effect. Nevertheless, the relationship between hepassocin and hyperthyroidism was still unknown. In the present study, a total of 36 subjects with Graves' disease were enrolled, and we found that the alanine aminotransferase (ALT) levels were significantly decreased in parallel with the decrement in serum hepassocin concentrations at 6 months after standard treatment for hyperthyroidism. In addition, HepG2 cell line was used to investigate the role of hepassocin in hyperthyroidism-induced hepatic dysfunction. Treatment of hepassocin recombinant protein in HepG2 cells dose-dependently decreased triiodothyronine (T3)-induced ALT and aspartate aminotransferase (AST) elevation. Moreover, hepassocin significantly increased the expression of phosphoenolpyruvate carboxykinase (PEPCK) in a dose-dependent manner. Deletion of hepassocin in HepG2 cells reversed the effects of T3 on PEPCK expressions. Furthermore, we found that T3 increased the expression of hepassocin through a hepatocyte nuclear factor 1α-dependent pathway. Taken together, these results indicated a compensatory increase in serum hepassocin might have a protective role in hyperthyroidism-induced hepatic dysfunction.
BACKGROUND: Since non-alcoholic fatty liver disease (NAFLD) is highly associated with obesity, cardiovascular disease, and diabetes, biomarkers for the diagnosis of NAFLD have become an important issue. Although cardiotrophin-1 (CT-1) has a protective effect on the liver in NAFLD animal models, the serum levels of CT-1 in human subjects with NAFLD were still unknown. OBJECTIVE: The present study aimed to investigate the relationship between the circulating concentration of CT-1 and the severity of hepatic steatosis graded by the value of the controlled attenuation parameter (CAP) in humans. DESIGN AND METHODS: The study was designed as a cross-sectional study, and a total of 182 subjects were enrolled. Hepatic steatosis measurement was carried out with a Firoscan® device and recorded by CAP. The enrolled study subjects were categorized into CAP < 238 dB/m, 238 ≤ CAP ≤ 259 dB/m, 260 ≤ CAP ≤ 290 dB/m, and CAP > 290 dB/m. Serum CT-1 concentrations were determined by enzyme-linked immunosorbent assay. The association between the serum CT-1 concentration and NAFLD was examined by multivariate linear regression analysis. RESULTS: Body mass index, percentage of body fat, systolic and diastolic blood pressure, alanine aminotransferase (ALT), cholesterol, triglyceride, hemoglobin A1c and homeostatic model assessment for insulin resistance (HOMA-IR) were significantly increased in groups with higher CAP value, whereas high-density lipoprotein cholesterol was significantly decreased. In addition, serum CT-1 concentrations were significantly decreased in subjects with higher CAP values. In multivariate linear regression models, including age, sex, body fat percentage, CAP, high sensitivity- C reactive protein, uric acid, creatinine, ALT, total cholesterol, and HOMA-IR, only age, CAP and uric acid independently associated with CT-1 levels. Moreover, having NAFLD was independently associated with CT-1 after adjustment for sex, obesity and type 2 diabetes. CONCLUSIONS: Serum CT-1 concentrations are decreased in subjects with NAFLD and negatively associated with CAP.
Monocytes are a major population of circulating immune cells that play a crucial role in producing pro-inflammatory cytokines in the body. The actions of monocytes are known to be influenced by the combinations and concentrations of certain fatty acids (FAs) in blood and dietary fats. However, systemic comparisons of the effects of FAs on cytokine secretion by monocytes have not be performed. In this study, we compared how six saturated FAs (SFAs), two monounsaturated FAs (MUFAs), and seven polyunsaturated FAs (PUFAs) modulate human THP-1 monocyte secretion of TNF, IL-1ß, and IL-6 in the absence or presence of lipopolysaccharide. SFAs generally stimulated resting THP-1 cells to secrete pro-inflammatory cytokines, with stearic acid being the most potent species. In contrast, MUFAs and PUFAs inhibited lipopolysaccharide-induced secretion of pro-inflammatory cytokines. Interestingly, the inhibitory potentials of MUFAs and PUFAs followed U-shaped (TNF and IL-1ß) or inverted U-shaped (IL-6) dose-response curves. Among the MUFAs and PUFAs that were analyzed, docosahexaenoic acid (C22:6 n-3) exhibited the largest number of double bonds and was found to be the most potent anti-inflammatory compound. Together, our findings reveal that the chemical compositions and concentrations of dietary FAs are key factors in the intricate regulation of monocyte-mediated inflammation.
Cytokines , Monocytes , Humans , Cytokines/pharmacology , Lipopolysaccharides/pharmacology , Interleukin-6/pharmacology , Fatty Acids/pharmacology , Fatty Acids, Unsaturated/pharmacology , Dietary Fats/pharmacology
Metabolic syndrome (MetS) is a major health issue worldwide accompanied by cardiovascular comorbidities. Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine expressed in cardiomyocytes, adipocytes, macrophages, and endothelial cells. Previous research in elderly subjects revealed that GDF-15 levels were associated with the MetS. However, the association between GDF-15 levels and MetS or its components in the non-elderly subjects remains unclear. In this study, a total of 279 subjects younger than 65-year-old with (n = 84) or without (n = 195) MetS were recruited. MetS was defined according to modified NCEP/ATP III criteria. The GDF-15 levels were measured by an enzyme-linked immunosorbent assay. A multiple linear regression analysis was conducted to identify factors independently associated with GDF-15 levels. Subjects with MetS had higher GDF-15 levels than those without MetS (median (interquartile range), 1.72 ng/mL (1.38, 2.26) vs. 1.63 ng/mL (1.27, 2.07), P = 0.037). With the number of MetS components increased, the GDF-15 levels increased significantly (P for trend = 0.005). Multiple linear regression analysis revealed that the presence of MetS was positively associated with the GDF-15 levels (ß = 0.132, P = 0.037). When substituting MetS with its components, only the presence of hyperglycemia was positively associated with the GDF-15 levels after adjustment for covariates (ß = 0.193, P = 0.003). Taken together, the presence of the MetS in non-elderly was associated with higher GDF-15 levels. Among the MetS components, only hyperglycemia was significantly associated with the GDF-15 levels. Future longitudinal studies will be needed to explore whether GDF-15 has the potential to be a biomarker of gluco-metabolic dysfunction in non-elderly subjects.
Hyperglycemia , Metabolic Syndrome , Humans , Middle Aged , Aged , Metabolic Syndrome/complications , Growth Differentiation Factor 15 , Endothelial Cells , Comorbidity , Risk Factors
Glucagon-like peptide 1 receptor agonist (GLP-1 RA) is a potent antidiabetic agent with cardiorenal and weight-losing benefits in patients with type 2 diabetes (T2D). The combination of GLP-1 RA with basal insulin has been suggested in several clinical studies as a useful treatment for intensifying insulin therapy in T2D. However, there has been no real-world evidence study comparing the glycemic effects of GLP-1 RAs add-on to background treatment with and without insulin. A retrospective study was performed in 358 patients with T2D who initiated liraglutide or dulaglutide. Among them, 147 patients were prior and concurrent insulin users, and 211 patients were non-insulin users. After 12 months of GLP-1 RA treatment, the changes in hemoglobin A1c (HbA1C) and body weight were evaluated. The effectiveness of GLP-1 RAs on HbA1C reduction was greater in insulin users than non-insulin users at 12 months (−1.17% vs. −0.76%; p = 0.018). There was no significant difference in body weight change between insulin users and non-insulin users at 12 months (−1.42 kg vs. −1.87 kg; p = 0.287). The proportion of responders (decrease of HbA1C > 1%) in insulin users was much higher than that in non-insulin users (48% vs. 37 %; p = 0.04). In insulin users, those who had increased insulin dosage at 12 months had significantly less HbA1C reduction than that of non-increased patients (−0.62% vs. −1.57%; p = 0.001). GLP-1 RAs provide superior glucose-lowering effects in insulin-treated patients compared with non-insulin-treated patients with T2D without significant differences in body weight decrease.
Recent advancements in microfluidics and high-throughput sequencing technologies have enabled recovery of paired H and L chains of Igs and VDJ and VJ chains of TCRs from thousands of single cells simultaneously in humans and mice. Despite rhesus macaques being one of the most well-studied model organisms for the human adaptive immune response, high-throughput single-cell immune repertoire sequencing assays are not yet available due to the complexity of these polyclonal receptors. We used custom primers that capture all known rhesus macaque Ig and TCR isotypes and chains that are fully compatible with a commercial solution for single-cell immune repertoire profiling. Using these rhesus-specific assays, we sequenced Ig and TCR repertoires in >60,000 cells from cryopreserved rhesus PBMCs, splenocytes, and FACS-sorted B and T cells. We were able to recover every Ig isotype and TCR chain, measure clonal expansion in proliferating T cells, and pair Ig and TCR repertoires with gene expression profiles of the same single cells. Our results establish the ability to perform high-throughput immune repertoire analysis in rhesus macaques at the single-cell level.
Immunoglobulins/genetics , Receptors, Antigen, T-Cell, alpha-beta/genetics , Receptors, Antigen, T-Cell, gamma-delta/genetics , VDJ Exons/genetics , Animals , Gene Expression Profiling , High-Throughput Nucleotide Sequencing , Macaca mulatta , Single-Cell Analysis , T-Lymphocytes/immunology , Transcriptome/genetics
Growth differentiation factor 15 (GDF15) is a stress-response cytokine which belongs to the transforming growth factor ß superfamily. Although GDF15 was initially found to have a role in metabolic diseases, the association between GDF15 and dysglycemic status remains inconclusive. Thus, the aim of this study was to examine the relationships between GDF15 and different glycemic statuses in non-obese subjects. We enrolled 502 non-obese subjects, among individuals who had normal glucose tolerance (NGT; n=125), isolated impaired fasting glucose (IFG; n=116), isolated impaired glucose tolerance (IGT; n=106), IFG plus IGT (n=27), and newly diagnosed diabetes (NDD; n=128). A multivariate linear regression analysis of GDF15 levels was used to find independent predictors. The median (IQR) GDF15 levels were 1641.0 (1187.0-1985.5) pg/mL, 1656.1 (1226.8-2379.7) pg/mL, 1487.8 (1145.9-1987.2) pg/mL, 1722.2 (1172.9-1939.0) pg/mL, and 2204.5 (1767.4-2919.1) pg/mL in NGT, IFG, IGT, IFG plus IGT, and NDD groups, respectively. The NDD group had significantly higher GDF15 levels than those with NGT, IFG, IGT, and IFG plus IGT. The IFG group had a significantly higher GDF15 value than the NGT group. In multivariate linear regression analysis, IFG (beta=0.145, 95% CI 192.487 to 740.937, p=0.001), NDD (beta=0.227, 95% CI 390.459 to 888.145, p<0.001), and high-sensitivity C reactive protein (beta=0.105, 95% CI 3.276 to 27.768, p=0.013) were independently associated with GDF15 levels. Non-obese subjects with isolated IFG and NDD had significantly higher GDF15 levels than those with NGT. In addition, A1C was independently associated with GDF15 levels. IFG and NDD, but not isolated IGT or IFG plus IGT, were positively associated with GDF15 levels.
Blood Glucose/analysis , C-Reactive Protein/metabolism , Glucose Intolerance/blood , Growth Differentiation Factor 15/blood , Prediabetic State/blood , Adult , Aged , Aged, 80 and over , C-Reactive Protein/analysis , Cross-Sectional Studies , Diabetes Mellitus/diagnosis , Female , Humans , Male , Middle Aged , Prediabetic State/metabolism
Hyaluronic acid (HA) is a glycosaminoglycan that was first isolated and identified from the vitreous body of a bull's eye. HA is ubiquitous in the soft connective tissues of animals and therefore has high tissue compatibility for use in medication. Because of HA's biological safety and water retention properties, it has many ophthalmology-related applications, such as in intravitreal injection, dry eye treatment, and contact lenses. Due to its broad range of applications, the identification and quantification of HA is a critical topic. This review article discusses current methods for analyzing HA. Contact lenses have become a widely used medical device, with HA commonly used as an additive to their production material, surface coating, and multipurpose solution. HA molecules on contact lenses retain moisture and increase the wearer's comfort. HA absorbed by contact lenses can also gradually release to the anterior segment of the eyes to treat dry eye. This review discusses applications of HA in ophthalmology.
Drug Delivery Systems , Dry Eye Syndromes/drug therapy , Hyaluronic Acid/therapeutic use , Ophthalmology , Contact Lenses/adverse effects , Dry Eye Syndromes/pathology , Humans
Although it was known that obesity is an independent risk factor for metabolic disorders including diabetes, the factors that link these diseases were obscure. The Hedgehog-interacting protein (Hhip) is a negative regulator in tissue remodeling, and inhibits the proliferation of adipocytes, and promotes their differentiation. In addition, Hhip was positively associated with diabetes. However, the relationship between Hhip and obesity in the human body remains unclear. An analysis of the relationship between Hhip and normal weight, overweight, and obesity levels. Participants receiving a physical checkup were recruited. Anthropometric and biochemical data were collected. Serum Hhip levels were determined by enzyme-linked immunosorbent assay (ELISA). Subjects were classified into normal-weight, overweight, and obese groups based on their body mass index (BMI). The association between Hhip and obesity was examined by multivariate linear regression analysis. In total, 294 subjects who were either of a normal weight (n = 166), overweight (n = 90), or obese (n = 38) were enrolled. Hhip concentrations were 6.51 ± 4.86 ng/mL, 5.79 ± 4.33 ng/mL, and 3.97 ± 3.4 ng/mL in normal-weight, overweight, and obese groups, respectively (p for trend = 0.032). Moreover, the regression analysis showed that BMI (ß = -0.144, 95% confidence interval (CI) = -0.397-0.046, p = 0.013) was negatively associated with Hhip concentrations after adjusting for sex and age. Being overweight (ß = -0.181, 95% CI = -3.311-0.400, p = 0.013) and obese (ß = -0.311, 95% CI = -6.393-2.384, p < 0.001) were independently associated with Hhip concentrations after adjusting for sex, age, fasting plasma glucose, the insulin level, and other cardiometabolic risk factors. Our results showed that overweight and obese subjects had lower Hhip concentrations than those of normal weight. Being overweight and obese were negatively associated with Hhip concentrations. Hhip might be a link between obesity and diabetes.
BACKGROUND: The aim of the present study was to investigate the risk factors for amputation in patients with diabetic foot ulcer (DFU). METHODS: Between 2012 and 2017, 646 patients with DFU were admitted to our diabetic foot care center. A retrospective chart review was performed, and the end point was limb salvage and minor or major amputation. Chi-square test, dependent t test, and a multivariate logistic regression analysis were performed to identify risk factors in patients with DFUs. RESULTS: A total of 399 male and 247 female patients (mean age 64.6 years) were included in this study, of whom 159 (24.6%) underwent lower limb amputation (minor, 17.5; major, 7.1%). Independent risk factors of amputation were peripheral arterial disease (PAD) (odds ratio [OR], 3.196; p < 0.001), C-reactive protein (CRP) level (OR, 1.046; p = 0.001), and hospital stay (OR, 1.019; p = 0.001). Subgroup analysis based on all patients with PAD who underwent amputation showed that endovascular intervention (OR, 0.271; p = 0.049) was a protective factor for major amputation in addition to CRP level (OR, 1.116; p = 0.008). CONCLUSION: DFU remains a major medical and public health issue. PAD, CRP level, and hospital stay are independent risk factors for amputation. Endovascular intervention is an independent protective factor against major amputation among patients with PAD who underwent amputation.
Amputation, Surgical , Diabetic Foot/physiopathology , Diabetic Foot/surgery , Foot Ulcer/surgery , Female , Humans , Male , Medical Audit , Middle Aged , Retrospective Studies , Risk Factors
To better understand the effects of transient thermal stress in an aquatic insect, we first identified static temperatures associated with fitness deficits, and then reared larvae from egg hatch to adulthood under diurnally variable regimens including daily forays into deleterious temperatures. We sampled mature larvae at the coolest and warmest portions of their respective regimens for RNA-seq analysis. Few transcripts (28) were differentially expressed when larvae oscillated between favorable temperatures, while 614 transcripts were differentially expressed when experiencing daily transient thermal stress. Transcripts associated with N-glycan processing were downregulated while those associated with lipid catabolism and chitin turnover were significantly upregulated in heat stressed larvae. An across-regimen comparison of differentially expressed transcripts among organisms sampled at comparable temperatures demonstrated that the effects of daily thermal stress persisted even when larvae were sampled at a more optimal temperature (806 differentially expressed transcripts). The chronically stressed population had reduced expression of transcripts related to ATP synthesis, mitochondrial electron chain functions, gluconeogenesis and glycolytic processes while transcripts associated with cell adhesion, synaptic vesicle transport, regulation of membrane potential and lipid biosynthesis increased. Comparisons of constant vs. variable temperatures revealed that the negative consequences of time spent at stressful temperatures were not offset by more time spent at optimal temperatures.
Ephemeroptera/physiology , Gene Expression Regulation , Heat-Shock Response/physiology , Temperature , Transcriptome , Animals , Ephemeroptera/genetics , Heat-Shock Response/genetics
Exposure of plants to abiotic stresses, whether individually or in combination, triggers dynamic changes to gene regulation. These responses induce distinct changes in phenotypic characteristics, enabling the plant to adapt to changing environments. For example, iron deficiency and heat stress have been shown to alter root development by reducing primary root growth and reducing cell proliferation, respectively. Currently, identifying the dynamic temporal coordination of genetic responses to combined abiotic stresses remains a bottleneck. This is, in part, due to an inability to isolate specific intervals in developmental time where differential activity in plant stress responses plays a critical role. Here, we observed that iron deficiency, in combination with temporary heat stress, suppresses the expression of iron deficiency-responsive pPYE::LUC (POPEYE::luciferase) and pBTS::LUC (BRUTUS::luciferase) reporter genes. Moreover, root growth was suppressed less under combined iron deficiency and heat stress than under either single stress condition. To further explore the interaction between pathways, we also created a computer vision pipeline to extract, analyze, and compare high-dimensional dynamic spatial and temporal cellular data in response to heat and iron deficiency stress conditions at high temporal resolution. Specifically, we used fluorescence light sheet microscopy to image Arabidopsis thaliana roots expressing CYCB1;1:GFP, a marker for cell entry into mitosis, every 20 min for 24 h exposed to either iron sufficiency, iron deficiency, heat stress, or combined iron deficiency and heat stress. Our pipeline extracted spatiotemporal metrics from these time-course data. These metrics showed that the persistency and timing of CYCB1;1:GFP signal were uniquely different under combined iron deficiency and heat stress conditions versus the single stress conditions. These metrics also indicated that the spatiotemporal characteristics of the CYCB1;1:GFP signal under combined stress were more dissimilar to the control response than the response seen under iron deficiency for the majority of the 24-h experiment. Moreover, the combined stress response was less dissimilar to the control than the response seen under heat stress. This indicated that pathways activated when the plant is exposed to both iron deficiency and heat stress affected CYCB1;1:GFP spatiotemporal function antagonistically.
Iron (Fe) is an essential nutrient for plants, but at the same time its redox properties can make it a dangerous toxin inside living cells. Homeostasis between uptake, use and storage of Fe must be maintained at all times. A small family of unique hemerythrin E3 ubiquitin ligases found in green algae and plants play an important role in avoiding toxic Fe overload, acting as negative regulators of Fe homeostasis. Protein interaction data showed that they target specific transcription factors for degradation by the 26S proteasome. It is thought that the activity of the E3 ubiquitin ligases is controlled by Fe binding to the N-terminal hemerythrin motifs. Here, we discuss what we have learned so far from studies on the HRZ (Hemerythrin RING Zinc finger) proteins in rice, the homologous BTS (BRUTUS) and root-specific BTSL (BRUTUS-LIKE) in Arabidopsis. A mechanistic model is proposed to help focus future research questions towards a full understanding of the regulatory role of these proteins in Fe homeostasis in plants.
