Development Of Disease Research Articles

Specificities of primary and secondary prevention of lower extremity artery disease: introduction to a series of reviews.

This article briefly discusses the risk factors for the development of lower extremity artery disease, namely smoking, diabetes mellitus, hyperlipidemia/dyslipidemia and hypertension. Each of these risk factors will be discussed in detail in forthcoming articles of the journal.

Sustained gut dysbiosis and intestinal inflammation show correlation with weight gain in person with chronic HIV infection on antiretroviral therapy

BackgroundPerson with human immunodeficiency virus type-1 (PWH) are prone to chronic inflammation due to residual viral production, even with antiretroviral therapy (ART), which increases the risk of age-related diseases. There is also limited information on changes in the intestinal environment of PWH during ART. In this longitudinal study, we investigated changes in the gut microbiota, persistence of chronic inflammation, interactions between the gut environment and inflammation, and metabolic changes in PWH using long-term ART.ResultsWe analyzed changes in clinical parameters and gut microbiota in 46 PWH over a mean period of 4 years to understand the influence of gut dysbiosis on inflammation. Overall, changes in the gut microbiota included a decrease in some bacteria, mainly involved in short-chain fatty acid (SCFA) production, and an increase in certain opportunistic bacteria. Throughout the study period, an increase in bacterial-specific metabolic activity was observed in the intestinal environment. Continued decline in certain bacteria belonging to the Clostridia class and metabolic changes in gut bacteria involved in glucose metabolism. Additionally, patients with a low abundance of Parabacteroides exhibited low bacterial alpha diversity and a significant increase in body mass index (BMI) during the study period. Monocyte chemoattractant protein 1, a marker of macrophage activation in the plasma, continued to increase from baseline (first stool collection timepoint) to follow-up (second stool collection timepoint), demonstrating a mild correlation with BMI. Elevated BMI was mild to moderately correlated with elevated levels of plasma interleukin 16 and chemokine ligand 13, both of which may play a role in intestinal inflammation and bacterial translocation within the gut microbiota. The rate of BMI increase correlated with the rate of decrease in certain SCFA-producing bacteria, such as Anaerostipes and Coprococcus 3.ConclusionOur data suggest that despite effective ART, PWH with chronic inflammation exhibit persistent dysbiosis associated with gut inflammation, resulting in a transition to an intestinal environment with metabolic consequences. Moreover, the loss of certain bacteria such as Parabacteroides in PWH correlates with weight gain and may contribute to the development of metabolic diseases.

Predictive value of the random forest model based on bioelectrical impedance analysis parameter trajectories for short-term prognosis in stroke patients

BackgroundThe short-term prognosis of stroke patients is mainly influenced by the severity of the primary disease at admission and the trend of disease development during the acute phase (1–7 days after admission).ObjectiveThe aim of this study is to explore the relationship between the bioelectrical impedance analysis (BIA) parameter trajectories during the acute phase of stroke patients and their short-term prognosis, and to investigate the predictive value of the prediction model constructed using BIA parameter trajectories and clinical indicators at admission for short-term prognosis in stroke patients.MethodsA total of 162 stroke patients were prospectively enrolled, and their clinical indicators at admission and BIA parameters during the first 1–7 days of admission were collected. A Group-Based Trajectory Model (GBTM) was employed to identify different subgroups of longitudinal trajectories of BIA parameters during the first 1–7 days of admission in stroke patients. The random forest algorithm was applied to screen BIA parameter trajectories and clinical indicators with predictive value, construct prediction models, and perform model comparisons. The outcome measure was the Modified Rankin Scale (mRS) score at discharge.ResultsPA in BIA parameters can be divided into four separate trajectory groups. The incidence of poor prognosis (mRS: 4–6) at discharge was significantly higher in the “Low PA Rapid Decline Group” (85.0%) than in the “High PA Stable Group “ (33.3%) and in the “Medium PA Slow Decline Group “(29.5%) (all P < 0.05). In-hospital mortality was the highest in the “Low PA Rapid Decline Group” (60%) compared with the remaining trajectory groups (P < 0.05). Compared with the prediction model with only clinical indicators (Model 1), the prediction model with PA trajectories (Model 2) demonstrated higher predictive accuracy and efficacy. The area under the receiver operating characteristic curve (AUC) of Model 2 was 0.909 [95% CI 0.863, 0.956], integrated discrimination improvement index (IDI), 0.035 (P < 0.001), and net reclassification improvement (NRI), 0.175 (P = 0.031).ConclusionPA trajectories during the first 1–7 days of admission are associated with the short-term prognosis of stroke patients. PA trajectories have additional value in predicting the short-term prognosis of stroke patients.

A personalized mRNA signature for predicting hypertrophic cardiomyopathy applying machine learning methods

Hypertrophic cardiomyopathy (HCM) may lead to cardiac dysfunction and sudden death. This study was designed to develop a HCM signature applying bioinformatics and machine learning methods. Data of HCM and normal tissues were obtained from public databases to screen differentially expressed genes (DEGs) using the R software limma package. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed for enrichment analysis of HCM-associated DEGs. Hub genes for HCM were determined using weighted gene co-expression network analysis (WGCNA) together with two machine learning algorithms (SVM-RFE and LASSO). Finally, we introduced a zebrafish model to simulate changes in the hub genes in the HCM and to observe their effects on cardiac disease development. The mRNA expression data from a total of 106 HCM tissues and 39 normal samples were collected and we screened 157 DEGs. Enrichment analysis showed that immune pathways played an important role in the pathogenesis of HCM. Three hub genes (FCN3, MYH6 and RASD1) were identified using WGCNA, SVM-RFE, and LASSO analysis. In a zebrafish model, knockdown of MYH6 and RASD1 resulted in cardiac malformations with reduced ventricular capacity and heart rate, which validated the clinical significance of these genes in the diagnosis of HCM. Based on machine learning algorithms, our study created a signature with potential impact on cardiac function and cardiac quality index for HCM. The current findings had important implications for the early diagnosis and treatment of HCM.

The pseudogene GBP1P1 suppresses influenza A virus replication by acting as a protein decoy for DHX9.

Recently, substantial evidence has demonstrated that pseudogene-derived long noncoding RNAs (lncRNAs) as regulatory RNAs have been implicated in basic physiological processes and disease development through multiple modes of functional interaction with DNA, RNA, and proteins. Here, we report an important role for GBP1P1, the pseudogene of guanylate-binding protein 1, in regulating influenza A virus (IAV) replication in A549 cells. GBP1P1 was dramatically upregulated after IAV infection, which is controlled by JAK/STAT signaling. Functionally, ectopic expression of GBP1P1 in A549 cells resulted in significant suppression of IAV replication. Conversely, silencing GBP1P1 facilitated IAV replication and virus production, suggesting that GBP1P1 is one of the interferon-inducible antiviral effectors. Mechanistically, GBP1P1 is localized in the cytoplasm and functions as a sponge to trap DHX9 (DExH-box helicase 9), which subsequently restricts IAV replication. Together, these studies demonstrate that GBP1P1 plays an important role in antagonizing IAV replication.IMPORTANCELong noncoding RNAs (lncRNAs) are extensively expressed in mammalian cells and play a crucial role as regulators in various biological processes. A growing body of evidence suggests that host-encoded lncRNAs are important regulators involved in host-virus interactions. Here, we define a novel function of GBP1P1 as a decoy to compete with viral mRNAs for DHX9 binding. We demonstrate that GBP1P1 induction by IAV is mediated by JAK/STAT activation. In addition, GBP1P1 has the ability to inhibit IAV replication. Importantly, we reveal that GBP1P1 acts as a decoy to bind and titrate DHX9 away from viral mRNAs, thereby attenuating virus production. This study provides new insight into the role of a previously uncharacterized GBP1P1, a pseudogene-derived lncRNA, in the host antiviral process and a further understanding of the complex GBP network.

Role of endothelial glycocalyx in central nervous system diseases and evaluation of the targeted therapeutic strategies for its protection: a review of clinical and experimental data.

Central nervous system (CNS) diseases, such as stroke, traumatic brain injury, dementia, and demyelinating diseases, are generally characterized by high morbidity and mortality, which impose a heavy economic burden on patients and their caregivers throughout their lives as well as on public health. The occurrence and development of CNS diseases are closely associated with a series of pathophysiological changes including inflammation, blood-brain barrier disruption, and abnormal coagulation. Endothelial glycocalyx (EG) plays a key role in these changes, making it a novel intervention target for CNS diseases. Herein, we review the current understanding of the role of EG in common CNS diseases, from the perspective of individual pathways/cytokines in pathophysiological and systematic processes. Furthermore, we emphasize the recent developments in therapeutic agents targeted toward protection or restoration of EG. Some of these treatments have yielded unexpected pharmacological results, as previously unknown mechanisms underlying the degradation and destruction of EG has been brought to light. Furthermore, the anti-inflammatory, anticoagulative, and antioxidation effects of EG and its protective role exerted via the blood-brain barrier have been recognized.

Sphingolipid and Trimethylamine-N-Oxide (TMAO) Levels in Women with Obesity after Combined Physical Training

Obesity causes metabolic changes, such as the development of cardiovascular diseases. Moreover, physical exercise promotes protection against these diseases. Thus, the objective of the present study was to evaluate whether combined physical training can improve the metabolic system of women with obesity, reducing plasma concentrations of trimethylamine N-oxide (TMAO) and sphingolipids, regardless of weight loss. Fourteen obese women (BMI 30–40 kg/m2), aged 20–40 years, sedentary, were submitted to 8 weeks of combined physical training (strength and aerobic exercises). The training was performed three times/week, 55 min/session, at 75–90% maximum heart rate. All participants were evaluated pre- and post-exercise intervention, and their body composition, plasma TMAO, creatinine, lipid profile, and sphingolipid concentrations were recorded. Maximum oxygen consumption (VO2max), Speed lactate threshold 1 (SpeedLT1), and Speed lactate threshold 2 (SpeedLT2) evaluated physical performance. Results: After combined exercise, it did not change body composition, but TMAO, total cholesterol, and sphingolipid concentrations significantly decreased (p &lt; 0.05). There was an increase in physical performance by improving VO2max, SpeedLT1, and SpeedLT2 (p &lt; 0.05). The combined physical exercise could induce cardiovascular risk protection by decreasing TMAO in obese women, parallel to physical performance improvement, independent of weight loss.

Exploring the therapeutic potential of garlic in alcoholic liver disease: a network pharmacology and experimental validation study

ObjectiveEmploying network pharmacology and molecular docking, the study predicts the active compounds in garlic and elucidates their mechanism in inhibiting the development of alcoholic liver disease (ALD). ALD is a global chronic liver disease with potential for hepatocellular carcinoma progression.MethodsThe main active ingredients and targets of garlic were identified through screening the TCMSP, TCM-ID, and ETCM databases. ALD disease targets were sourced from DisGeNET, GeneCards, and DiGSeE databases, and intervention targets for garlic were determined through intersections. Protein interaction networks were constructed using the STRING platform, and GO and KEGG pathway enrichment analyses were performed with R software. The garlic component-disease-target network was established using Cytoscape software. Validation of active ingredients against core targets was conducted through molecular docking simulations using AutoDock Vina software. Expression validation of core targets was carried out using human sequencing data of ALD obtained from the GEO database.ResultsIntegration of garlic drug targets with ALD disease targets identified 83 target genes. Validation through an alcohol-induced ALD mouse model supported certain network pharmacology findings, suggesting that garlic may impede disease progression by mitigating the inflammatory response and promoting ethanol metabolism.ConclusionThis study provides insights into the potential therapeutic mechanisms of garlic in inhibiting ALD development. The identified active ingredients offer promising avenues for further investigation and development of treatments for ALD, emphasizing the importance of botanical remedies in liver disease management.

Long-term risk of autoimmune diseases after mRNA-based SARS-CoV2 vaccination in a Korean, nationwide, population-based cohort study

The long-term association between mRNA-based coronavirus disease 2019 (COVID-19) vaccination and the development of autoimmune connective tissue diseases (AI-CTDs) remains unclear. In this nationwide, population-based cohort study involving 9,258,803 individuals, we aim to determine whether the incidence of AI-CTDs is associated with mRNA vaccination. The study spans over 1 year of observation and further analyses the risk of AI-CTDs by stratifying demographics and vaccination profiles and treating booster vaccination as time-varying covariate. We report that the risk of developing most AI-CTDs did not increase following mRNA vaccination, except for systemic lupus erythematosus with a 1.16-fold risk in vaccinated individuals relative to controls. Comparable results were reported in the stratified analyses for age, sex, mRNA vaccine type, and prior history of non-mRNA vaccination. However, a booster vaccination was associated with an increased risk of some AI-CTDs including alopecia areata, psoriasis, and rheumatoid arthritis. Overall, we conclude that mRNA-based vaccinations are not associated with an increased risk of most AI-CTDs, although further research is needed regarding its potential association with certain conditions.

Exploring factors associated with non-alcoholic fatty liver disease using longitudinal MRI

BackgroundTo identify factors associated with non-alcoholic fatty liver disease over a 5-year period.MethodsThree hundred seven participants, including 165 women, with a mean age of 55.6 ± 12.0 years underwent continuous quantitative MRI of the liver using the proton-density fat fraction (PDFF). The liver’s fat fractions were determined at baseline and 5 years later, and the frequency of participants who developed fatty liver disease and potential influencing factors were explored. Based on significant factors, a model was generated to predict the development of fatty liver disease.ResultsAfter excluding participants with pre-existing fatty liver, the baseline PDFF of 3.1 ± 0.9% (n = 190) significantly increased to 7.67 ± 3.39% within 5 years (p < 0.001). At baseline, age (OR = 1.04, p = 0.006, CI = 1.01–1.07), BMI (OR = 1.11, p = 0.041, CI = 1.01–1.23), and waist circumference (OR = 1.05, p = 0.020, CI = 1.01–1.09) were identified as risk factors. Physical activity was negatively associated (OR = 0.43, p = 0.049, CI = 0.18–0.99). In the prediction model, age, physical activity, diabetes mellitus, diastolic blood pressure, and HDL-cholesterol remained as independent variables. Combining these risk factors to predict the development of fatty liver disease revealed an AUC of 0.7434.ConclusionsWithin a five-year follow-up, one-quarter of participants developed fatty liver disease influenced by the triggering factors of age, diabetes mellitus, low HDL-cholesterol, and diastolic blood pressure. Increased physical activity has a protective effect on the development of fatty liver.

The Association of Preoperative Bone Mineral Density and Outcomes after Anterior Cervical Discectomy and Fusion: A Systematic Review.

This is a systematic review. To evaluate anterior cervical discectomy and fusion (ACDF) outcomes and complications as a function of preoperative bone mineral density (BMD). Preoperative BMD optimization is commonly initiated before lumbar spinal fusion, but the effects of BMD on ACDF are less known. Consequently, it remains unclear whether preoperative BMD optimization is recommended before ACDF. This systematic review included relevant clinical articles using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed, Web of Science, SCOPUS, and MEDLINE from database inception until October 1, 2023. Eligible studies included those evaluating low BMD and outcomes after ACDF. All articles were graded using the Methodological Index for Non-Randomized Studies (MINORS) scale and Critical Appraisal Skills Programme (CASP) assessment tools. The initial retrieval yielded 4271 articles for which 4 articles with 671 patients were included in the final analysis. The mean patient age was 56.4 ± 3.9 years, and 331 patients (49.3%) were female. A total of 265 (39.5%) patients had low BMD (T score<-1.0) before ACDF. Preoperative low BMD was associated with cage subsidence in single-level ACDF (odds ratio (OR) 2.57; P=0.063; 95% Confidence Interval (CI): 0.95-6.95), but this result did not reach statistical significance. Osteoporosis (T score<-2.5) was associated with the development of adjacent segment disease following ACDF (OR 4.41; P<0.01; 95% CI: 1.98-9.83). Low pre-operative BMD was associated with reoperation within 2 years (P<.05) and strongly associated with pseudarthrosis (OR: 11.01; P=0.002; 95% CI 2.4-49.9). Patients with low BMD who undergo ACDF have higher rates of subsidence, adjacent segment disease, and pseudarthrosis than those with normal BMD. Given the individual and system-wide burdens associated with these complications, some patients may benefit from preoperative BMD screening and optimization before undergoing ACDF.

Standardization and clinical applications of retinal imaging biomarkers for cardiovascular disease: a Roadmap from an NHLBI workshop.

The accessibility of the retina with the use of non-invasive and relatively low-cost ophthalmic imaging techniques and analytics provides a unique opportunity to improve the detection, diagnosis and monitoring of systemic diseases. The National Heart, Lung, and Blood Institute conducted a workshop in October 2022 to examine this concept. On the basis of the discussions at that workshop, this Roadmap describes current knowledge gaps and new research opportunities to evaluate the relationships between the eye (in particular, retinal biomarkers) and the risk of cardiovascular diseases, including coronary artery disease, heart failure, stroke, hypertension and vascular dementia. Identified gaps include the need to simplify and standardize the capture of high-quality images of the eye by non-ophthalmic health workers and to conduct longitudinal studies using multidisciplinary networks of diverse at-risk populations with improved implementation and methods to protect participant and dataset privacy. Other gaps include improving the measurement of structural and functional retinal biomarkers, determining the relationship between microvascular and macrovascular risk factors, improving multimodal imaging 'pipelines', and integrating advanced imaging with 'omics', lifestyle factors, primary care data and radiological reports, by using artificial intelligence technology to improve the identification of individual-level risk. Future research on retinal microvascular disease and retinal biomarkers might additionally provide insights into the temporal development of microvascular disease across other systemic vascular beds.

Effect of bariatric surgery in the body burden of persistent and non-persistent pollutants: longitudinal study in a cohort of morbidly obese patients

IntroductionObesity is a pathological state that involves the dysregulation of different metabolic pathways and adipose tissue cells, constituting a risk factor for the development of other diseases. Bariatric surgery is the most effective treatment. The study of the behavior of pollutants in situations of extreme weight loss can provide biomonitoring information and tools to manage diseases of environmental etiology.AimTo determine the prevalence of serum persistent and non-persistent pollutants in obese patients subjected to bariatric surgery and analyze the impact of sociodemographic variables on these changes.MethodsGC-MS/MS and UHPLC-MS/MS were utilized to determine the detection rates and concentrations of 353 compounds, including persistent organic pollutants (POPs), pesticides, pharmaceuticals, and rodenticide, in serum samples of 59 obese patients before and after undergoing bariatric surgery.ResultsDetection rates of p,p’-DDE, HCB, β-HCH, naphthalene, phenanthrene and PCB congeners 138, 153 and 180 significantly increased due to surgery-induced weight loss. Serum levels of p,p’-DDE, PCB-138, PCB-153 and PCB-180 also increased after surgery. Correlations between naphthalene levels, weight loss, variation of total lipids and time after surgery were found. Additionally, correlations were observed between concentrations of PCB-138 and weight loss, and between phenanthrene levels and reduction of total lipids. No statistically significant differences were observed for other groups of contaminants, pharmaceuticals and other chemicals included in the quantification methods.ConclusionsIncrement of POPs was observed after bariatric surgery. Serum concentrations of POPs after surgery were influenced by adiposity-related variables. Although biomonitoring studies show a decreasing tendency of exposure, rapid weight loss leads to an increase of circulating POPs. Further research on the interplay between adipose tissue, POPs and peripheral organs is required.

Preventive effects of early immunosuppressive treatment on the development of interstitial lung disease in systemic sclerosis.

Hypothesizing that early treatment yields improved prognosis, we aimed to investigate how the timing of immunosuppressive treatment relates to interstitial lung disease (ILD) development and the course of pulmonary function in systemic sclerosis (SSc). A cohort was created using data from the EUSTAR database and Nijmegen Systemic Sclerosis cohort, including adult patients who started their first immunosuppressive treatment (ie mycophenolate mofetil, methotrexate, cyclophosphamide, tocilizumab or rituximab) after SSc diagnosis, and no signs of ILD on high-resolution CT. ILD-free survival and the course of forced vital capacity % predicted (ppFVC) were assessed for up to 5 years follow-up comparing patients who started early (disease duration ≤ 3 years) vs late with immunosuppression. 1052 patients met the eligibility criteria. The early treatment group (n = 547, 52%) showed a higher prevalence of male sex, diffuse cutaneous subtype (53.1% vs 36.5%), and anti-topoisomerase-I antibody (ATA, 51.1% vs 42.7%). Most patients were treated with methotrexate (60.1%), whereas only a few patients were treated with biologicals (1.7%). The incidence of ILD was 46.6% after mean (SD) 3.6(1.4) years; the hazards ratio for ILD in the early treatment group was 1.13 (95% CI: 0.93-1.38) after adjustment for confounders. PpFVC trajectories were comparable between groups. Our findings did not confirm a preventive role of early initiation of immunosuppressive therapy vs late initiation on ILD development. However, our findings should be interpreted with caution, considering the high inflammatory, ATA-positive enriched nature of the cohort, confounding by indication, and very few patients were treated with biologicals.

Surgical outcomes and complications associated with ovariectomy in the southern stingray Hypanus americanus

Southern stingrays (Hypanus americanus) are relatively large rays that are common and popular in public aquariums because of their size and gentle nature. In aquariums, as well as in the wild, female southern stingrays are fecund. They have a short gestation cycle and can sustain multiple pregnancies each year, each culminating with 2–10 young. This reproductive rate could quickly outpace capacity in managed care and result in a ray surplus. To prevent overpopulation, many aquaria have resorted to single sex groups with a preference for female-only populations. This is an effective way to control population growth, but forces the maintenance of two separated populations of rays; for females this interrupts normal reproductive cycling and replaces it with a protracted non-pregnant condition. An additional consideration is development of reproductive disease in females which is recognized by an enlarged, misshapen, and congested ovary with an abundance of cystic structures and an enlarged uterus with a thickened wall that is often filled with histotroph despite a non-pregnant status. There are no effective long-lasting medical treatments for this type of reproductive disease and mortality is often the result. This report describes a surgical technique for ovariectomy in southern stingrays including outcomes and complications. Ovariectomy as a surgical method prevents unwanted reproduction and has the benefit of reducing reproductive pathologies commonly observed in southern stingrays as they age. Seven stingrays 1–5.2 years old and 42–83.5 cm disc width underwent ovariectomy. After anesthesia, the ovary and a small amount of epigonal was excised via a left para-lumbar incision. Four of the seven rays survived five or more years post-procedure. Two rays died acutely of coelomitis and one ray died of complications unrelated to the procedure. This report details a surgical procedure for ovariectomy in southern stingrays including outcomes, complications, and recommendations.

Multiplexed spatial transcriptomics methods and the application of expansion microscopy

While spatial transcriptomics has undeniably revolutionized our ability to study cellular organization, it has driven the development of a great number of innovative transcriptomics methods, which can be classified into in situ sequencing (ISS) methods, in situ hybridization (ISH) techniques, and next-generation sequencing (NGS)-based sequencing with region capture. These technologies not only refine our understanding of cellular processes, but also open up new possibilities for breakthroughs in various research domains. One challenge of spatial transcriptomics experiments is the limitation of RNA detection due to optical crowding of RNA in the cells. Expansion microscopy (ExM), characterized by the controlled enlargement of biological specimens, offers a means to achieve super-resolution imaging, overcoming the diffraction limit inherent in conventional microscopy and enabling precise visualization of RNA in spatial transcriptomics methods. In this review, we elaborate on ISS, ISH and NGS-based spatial transcriptomic protocols and on how performance of these techniques can be extended by the combination of these protocols with ExM. Moving beyond the techniques and procedures, we highlight the broader implications of transcriptomics in biology and medicine. These include valuable insight into the spatial organization of gene expression in cells within tissues, aid in the identification and the distinction of cell types and subpopulations and understanding of molecular mechanisms and intercellular changes driving disease development.

Hepatokines: unveiling the molecular and cellular mechanisms connecting hepatic tissue to insulin resistance and inflammation.

Insulin resistance arising from Non-Alcoholic Fatty Liver Disease (NAFLD) stands as a prevalent global ailment, a manifestation within societies stemming from individuals' suboptimal dietary habits and lifestyles. This form of insulin resistance emerges as a pivotal factor in the development of type 2 diabetes mellitus (T2DM). Emerging evidence underscores the significant role of hepatokines, as hepatic-secreted hormone-like entities, in the genesis of insulin resistance and eventual onset of type 2 diabetes. Hepatokines exert influence over extrahepatic metabolism regulation. Their principal functions encompass impacting adipocytes, pancreatic cells, muscles, and the brain, thereby playing a crucial role in shaping body metabolism through signaling to target tissues. This review explores the most important hepatokines, each with distinct influences. Our review shows that Fetuin-A promotes lipid-induced insulin resistance by acting as an endogenous ligand for Toll-like receptor 4 (TLR-4). FGF21 reduces inflammation in diabetes by blocking the nuclear translocation of nuclear factor-κB (NF-κB) in adipocytes and adipose tissue, while also improving glucose metabolism. ANGPTL6 enhances AMPK and insulin signaling in muscle, and suppresses gluconeogenesis. Follistatin can influence insulin resistance and inflammation by interacting with members of the TGF-β family. Adropin show a positive correlation with phosphoenolpyruvate carboxykinase 1 (PCK1), a key regulator of gluconeogenesis. This article delves into hepatokines' impact on NAFLD, inflammation, and T2DM, with a specific focus on insulin resistance. The aim is to comprehend the influence of these recently identified hormones on disease development and their underlying physiological and pathological mechanisms.

Mitochondrial complex-1 as a therapeutic target for cardiac diseases.

Mitochondrial dysfunction is critical for the development and progression of cardiovascular diseases (CVDs). Complex-1 (CI) is an essential component of the mitochondrial electron transport chain that participates in oxidative phosphorylation and energy production. CI is the largest multisubunit complex (~ 1 Mda) and comprises 45 protein subunits encoded by seven mt-DNA genes and 38 nuclear genes. These subunits function as the enzyme nicotinamide adenine dinucleotide hydrogen(NADH): ubiquinone oxidoreductase. CI dysregulation has been implicated in various CVDs, including heart failure, ischemic heart disease, pressure overload, hypertrophy, and cardiomyopathy. Several studies demonstrated that impaired CI function contributes to increased oxidative stress, altered calcium homeostasis, and mitochondrial DNA damage in cardiac cells, leading to cardiomyocyte dysfunction and apoptosis. CI dysfunction has been associated with endothelial dysfunction, inflammation, and vascular remodeling, critical processes in developing atherosclerosis and hypertension. Although CI is crucial in physiological and pathological conditions, no potential therapeutics targeting CI are available to treat CVDs. We believe that a lack of understanding of CI's precise mechanisms and contributions to CVDs limits the development of therapeutic strategies. In this review, we comprehensively analyze the role of CI in cardiovascular health and disease to shed light on its potential therapeutic target role in CVDs.

Dicyanisophorone-based viscosity fluorescent probe and its fluorescence imaging in cells and zebrafish

Cellular viscosity is a critical parameter for maintaining normal cellular functions, and its abnormalities are associated with the occurrence and development of various diseases. Therefore, real-time monitoring of cellular viscosity is of significant importance for understanding viscosity-related biological functions and revealing the pathological mechanisms of diseases. In this study, we developed a novel fluorescence probe (IP-HBO) by hybridizing dicyanisophorone with 2-(2-hydroxyphenyl)benzoxazole for monitoring of cellular microenvironment and viscosity changes in zebrafish. The probe IP-HBO combines the principles of molecular rotors and enhanced solid-state fluorescence properties, demonstrating highly specific responsiveness to viscosity, long-wavelength emission, large Stokes shift, and excellent photostability. It has been successfully employed for fluorescence imaging of viscosity in live HeLa cells and zebrafish. The construction of this probe provides a new tool for gaining insights into viscosity-related biological processes and disease mechanisms within cells.

A novel approach to managing facility airborne diseases: suppressing air pathogens with smoke aerosols generated from fungicide phase transition.

Environmental microorganisms are major contributors to the development and spread of disease. Chemical disinfection can inhibit pathogens and play a preventive role against diseases. In agriculture, prolonging the floating time of chemical pesticides in the air has a positive effect on the control of airborne diseases. However, the interaction of chemical pesticides with airborne pathogens is not yet known. Here, triazole fungicide was transformed into stable smoke aerosols in order to assess the feasibility of employing phase transition release pesticides for air disinfection. The phase transition had a minimal impact on hexaconazole (Hexa) and myclobutanil (Mycl), with their smoke formation rates remaining consistently >90%. In microscopic morphology, triadimenol (Tria) and epoxiconazole (Epox) are solid, and tebuconazole (Tebu), Hexa, Mycl and difenoconazole (Dife) are liquid. Liquid smoke has advantages over solid smoke in the inhibition of environmental pathogens. The floatability and spatial distribution of fungicide aerosol were optimized by the combination of smoke particles with different properties, so that the fungicide aerosol could meet the conditions of practical application. In practical applications, smoke exhibits a gentler deposition process at the target interface compared to spray, along with a more homogeneous distribution of fungicides. Moreover, fungicide smoke demonstrates superior control efficacy and leaves behind lower residual amounts on fruit. In conclusion, the implementation of fungicide phase transition as a smoke aerosol offers a viable approach to effectively suppress pathogen aerosols and enhance the control of airborne diseases. © 2024 Society of Chemical Industry.