Tacrolimus-Induced Hepatic Vein Occlusive Disease After Deceased Donor Liver Transplantation: A Case Report.

Advancements in surgical techniques and the optimization of immunosuppression have boosted organ transplant survival rates; however, liver transplant recipients still risk complications such as hepatic vein occlusive disease (HVOD), also called sinusoidal obstruction syndrome. Rare but potentially fatal HVOD damages endothelial cells due to factors like chemotherapy, stem cell transplantation, and certain medications such as azathioprine and tacrolimus. Typically, HVOD presents with distinct clinical symptoms, including ascites, jaundice, and significant weight gain. Herein, we present the case of a 66-year-old male with decompensated liver cirrhosis due to hepatitis C virus infection. The patient underwent a deceased donor liver transplantation at our center. Unfortunately, 4 months after the transplant, he experienced progressive dyspnea and developed right pleural effusion. Abdominal computed tomography and a liver biopsy confirmed the diagnosis of HVOD, likely induced by tacrolimus. After stopping tacrolimus, we observed a significant decrease in ascites and remission of the patient's clinical symptoms of abdominal distention and dyspnea; subsequently, we introduced cyclosporine. In this report, we describe this specific patient's case and discuss HVOD, including its diagnosis and management.

HIGH THROUGHPUT QUANTITATION OF HUMAN NEUTROPHIL RECRUITMENT AND FUNCTIONAL RESPONSES IN AN AIR-BLOOD BARRIER ARRAY.

Dysregulated neutrophil recruitment drives many pulmonary diseases, but most preclinical screening methods are unsuited to evaluate pulmonary neutrophilia, limiting progress towards therapeutics. Namely, high throughput therapeutic screening systems typically exclude critical neutrophilic pathophysiology, including blood-to-lung recruitment, dysfunctional activation, and resulting impacts on the air-blood barrier. To meet the conflicting demands of physiological complexity and high throughput, we developed an assay of 96-well Leukocyte recruitment in an Air-Blood Barrier Array (L-ABBA-96) that enables in vivo -like neutrophil recruitment compatible with downstream phenotyping by automated flow cytometry. We modeled acute respiratory distress syndrome (ARDS) with neutrophil recruitment to 20 ng/mL epithelial-side interleukin 8 (IL-8) and found a dose dependent reduction in recruitment with physiologic doses of baricitinib, a JAK1/2 inhibitor recently FDA-approved for severe COVID-19 ARDS. Additionally, neutrophil recruitment to patient-derived cystic fibrosis sputum supernatant induced disease-mimetic recruitment and activation of healthy donor neutrophils and upregulated endothelial e-selectin. Compared to 24-well assays, the L-ABBA-96 reduces required patient sample volumes by 25 times per well and quadruples throughput per plate. Compared to microfluidic assays, the L-ABBA-96 recruits two orders of magnitude more neutrophils per well, enabling downstream flow cytometry and other standard biochemical assays. This novel pairing of high-throughput in vitro modeling of organ-level lung function with parallel high-throughput leukocyte phenotyping substantially advances opportunities for pathophysiological studies, personalized medicine, and drug testing applications.

Targeting the nuclear long noncoding transcript LSP1P5 abrogates extracellular matrix deposition by trans-upregulating CEBPA in keloids.

Keloids are characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix (ECM) and are a major global health care burden among cutaneous diseases. However, the function of long noncoding RNA (lncRNA)-mediated ECM remodeling during the pathogenesis of keloids is still unclear. Herein, we identified a long noncoding transcript, namely, lymphocyte-specific protein 1 pseudogene 5 (LSP1P5), that modulates ECM component deposition in keloids. First, high-throughput transcriptome analysis showed that LSP1P5 was selectively upregulated in keloids and correlated with more severe disease in a clinical keloid cohort. Therapeutically, the attenuation of LSP1P5 significantly decreased the expression of ECM markers (COL1, COL3, and FN1) both in vitro and in vivo. Intriguingly, an antifibrotic gene, CCAAT enhancer binding protein alpha (CEBPA), is a functional downstream candidate of LSP1P5. Mechanistically, LSP1P5 represses CEBPA expression by hijacking Suppressor of Zeste 12 to the promoter of CEBPA, thereby enhancing the polycomb repressive complex 2-mediated H3K27me3 and changing the chromosomal opening status of CEBPA. Taken together, these findings indicate that targeting LSP1P5 abrogates fibrosis in keloids through epigenetic regulation of CEBPA, revealing a novel antifibrotic therapeutic strategy that bridges our current understanding of lncRNA regulation, histone modification and ECM remodeling in keloids.

Using extracorporeal membrane oxygenation in donations after cardiac death or brain death: A single-center experience and long-term outcome.

Aims: The use of extended criteria donors is a routine practice that sometimes involves extracorporeal membrane oxygenation (ECMO) in donations after cardiac death or brain death. Methods: We performed a retrospective study in a single center from January 2006 to December 2019. The study included 90 deceased donor liver transplants. The patients were divided into three groups: the donation after brain death (DBD) group (n = 58, 64.4%), the DBD with ECMO group (n = 11, 12.2%) and the donation after cardiac death (DCD) with ECMO group (n = 21, 23.3%). Results: There were no significant differences between the DBD with ECMO group and the DBD group. When comparing the DCD with ECMO group and the DBD group, there were statistically significant differences for total warm ischemia time (p < 0.001), total cold ischemia time (p = 0.023), and split liver transplantation (p < 0.001), and there was significantly poor recovery in regard to total bilirubin level (p = 0.027) for the DCD with ECMO group by repeated measures ANOVA. The 5-year survival rates of the DBD, DBD with ECMO, and DCD with ECMO groups were 78.1%, 90.9%, and 75.6%, respectively. The survival rate was not significantly different when comparing the DBD group to either the DBD with ECMO group (p = 0.435) or the DCD with ECMO group (p = 0.310). Conclusions: Using ECMO in donations after cardiac death or brain death is a good technology, and it contributed to 35.6% of the liver graft pool.

Innovative analysis of diazepam, zolpidem and their main metabolites in human urine by micelle-to-solvent stacking in capillary electrophoresis.

Diazepam and zolpidem are the most widely used medications for managing insomnia. However, significant concerns regarding the potential risks of misuse and abuse problems arose in many literatures. While urine analysis is a valuable diagnostic tool, a challenge arises from the fact that some parent drugs may remain undetectable in urine. This necessitates concurrent monitoring of their metabolites. Here, we described an innovative on-line sample preconcentration technique known as micelle to solvent stacking (MSS) for the analysis of diazepam, zolpidem, and their main metabolites in urine. Several key parameters warrant further discussion to optimize the MSS model, enhancing its performance in terms of sensitivity and resolution. After optimizing the conditions, we conducted a validation test, achieving high correlation coefficients (greater than 0.9977) for intra-day and inter-day regression lines. Additionally, both the relative standard deviation (RSD) and relative error (RE) remained below 6.10% and 12.55%, respectively. The limits of detection (LODs, S/N = 3) for all five analytes ranged from 2.0 to 56 ng/mL. Compared to the conventional capillary zone electrophoresis method, this new approach exhibited remarkable sensitivity enhancements, ranging from 123 to 235-fold. Upon applying this method to actual urine samples from patients, we successfully detected nordiazepam, zolpidem, and its metabolites. This simple and sensitive approach has promising applications in supporting patient medication safety and bolstering forensic investigations.

Inhibition of pathogenic bacterial carbonic anhydrases by monothiocarbamates.

Carbonic anhydrases (CAs) from the pathogenic bacteria Nesseria gonorrhoeae and vancomycin-resistant enterococci (VRE) have recently been validated as antibacterial drug targets. Here we explored the inhibition of the α-CA from N. gonorrhoeae (α-NgCA), of α- and γ-class enzymes from Enterococcus faecium (α-EfCA and γ-EfCA) with a panel of aliphatic, heterocyclic and aryl-alkyl primary/secondary monothiocarbamates (MTCs). α-NgCA was inhibited in vitro with KIs ranging from 0.367 to 0.919 µM. The compounds inhibited the α-EfCA and γ-EfCA with KI ranges of 0.195-0.959 µM and of 0.149-1.90 µM, respectively. Some MTCs were also investigated for their inhibitory effects on the growth of clinically-relevant N. gonorrhoeae and VRE strains. No inhibitory effects on the growth of VRE were noted for all MTCs, whereas one compound (13) inhibited the growth N. gonorrhoeae strains at concentrations ranging from 16 to 64 µg/mL. This suggests that compound 13 may be a potential antibacterial agent against N. gonorrhoeae.

Smart and versatile biomaterials for cutaneous wound healing.

The global increase of cutaneous wounds imposes huge health and financial burdens on patients and society. Despite improved wound healing outcomes, conventional wound dressings are far from ideal, owing to the complex healing process. Smart wound dressings, which are sensitive to or interact with changes in wound condition or environment, have been proposed as appealing therapeutic platforms to effectively facilitate wound healing. In this review, the wound healing processes and features of existing biomaterials are firstly introduced, followed by summarizing the mechanisms of smart responsive materials. Afterwards, recent advances and designs in smart and versatile materials of extensive applications for cutaneous wound healing were submarined. Finally, clinical progresses, challenges and future perspectives of the smart wound dressing are discussed. Overall, by mapping the composition and intrinsic structure of smart responsive materials to their individual needs of cutaneous wounds, with particular attention to the responsive mechanisms, this review is promising to advance further progress in designing smart responsive materials for wounds and drive clinical translation.

Method Development for Determination of Doripenem in Human Plasma via Capillary Electrophoresis Coupled with Field-Enhanced Sample Stacking and Sweeping.

In this study, we established a novel capillary electrophoresis method for monitoring the concentration of doripenem in human plasma. As a time-dependent antibiotic, doripenem maximizes its antibacterial effects and minimizes the potential for antibiotic resistance through careful therapeutic drug monitoring. Two online preconcentration techniques, field-enhanced sample stacking (FESS) and sweeping, were coupled to enhance the detection sensitivity. Briefly, an uncoated fused silica capillary (40 cm × 50 µm i.d) was rinsed with a high conductivity buffer (HCB) composed of 150 mM phosphate buffer (NaH2PO4, pH 2.5) and 20% methanol. A large sample plug prepared in a low-conductivity phosphate buffer (50 mM NaH2PO4, pH 2.5) was then hydrodynamically injected (5 psi, 80 s) into the capillary. Under an applied voltage of -30 kV, the analyte was accumulated at the FESS boundary and swept by the negatively charged micelles toward the UV detector. Plasma samples were pretreated by solid-phase extraction (SPE) to eliminate endogenous interferences. The validation results demonstrated a high coefficient of determination (r2 > 0.9995) for the regression curve with impressive precision and accuracy: relative standard deviation (RSD) <5.86% and relative error <4.63%. The limit of detection (LOD, S/N = 3) for doripenem was determined to be 0.4 µg/mL. Compared to the conventional micellar electrokinetic chromatography method, our developed method achieved a sensitivity enhancement of up to 488-fold for doripenem. Furthermore, the newly developed method successfully quantified doripenem concentrations in plasma samples obtained from patients accepting doripenem regimens, proving its application potential in the clinical realm.

ALKBH5-mediated m6A demethylation fuels cutaneous wound re-epithelialization by enhancing PELI2 mRNA stability.

BACKGROUND: Impaired wound re-epithelialization contributes to cutaneous barrier reconstruction dysfunction. Recently, N6-methyladenosine (m6A) RNA modification has been shown to participate in the determination of RNA fate, and its aberration triggers the pathogenesis of numerous diseases. Howbeit, the function of m6A in wound re-epithelialization remains enigmatic. METHODS: Alkbh5‒/‒ mouse was constructed to study the rate of wound re-epithelialization after ALKBH5 ablation. Integrated high-throughput analysis combining methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq was used to identify the downstream target of ALKBH5. In vitro and in vivo rescue experiments were conducted to verify the role of the downstream target on the functional phenotype of ALKBH5-deficient cells or animals. Furthermore, the interacting reader protein and regulatory mechanisms were determined through RIP-qPCR, RNA pull-down, and RNA stability assays. RESULTS: ALKBH5 was specifically upregulated in the wound edge epidermis. Ablation of ALKBH5 suppressed keratinocyte migration and resulted in delayed wound re-epithelialization in Alkbh5‒/‒ mouse. Integrated high-throughput analysis revealed that PELI2, an E3 ubiquitin protein ligase, serves as the downstream target of ALKBH5. Concordantly, exogenous PELI2 supplementation partially rescued keratinocyte migration and accelerated re-epithelialization in ALKBH5-deficient cells, both in vitro and in vivo. In terms of its mechanism, ALKBH5 promoted PELI2 expression by removing the m6A modification from PELI2 mRNA and enhancing its stability in a YTHDF2-dependent manner. CONCLUSIONS: This study identifies ALKBH5 as an endogenous accelerator of wound re-epithelialization, thereby benefiting the development of a reprogrammed m6A targeted therapy for refractory wounds.

Early Experience of Patients with left Bundle Branch Block Corrected through Left Bundle Branch Area Pacing Compared with Conventional Right Ventricular Pacing: A Single-Center Retrospective Study.

Background: Left bundle branch area pacing (LBBAP) has the advantages of narrow QRS duration, rapid peak left ventricular (LV) activation, and LV dyssynchrony correction with a low, stable pacing output. Here we report our experience with patients undergoing LBBAP with a left bundle branch block (LBBB) for clinically indicated pacemaker or cardiac resynchronization therapy implantation. We compared the initial follow-up data of these patients and patients undergoing conventional right ventricular pacing (RVP). Methods: This retrospective study was performed between January 2017 and December 2020 and recruited 19 consecutive patients (mean age: 63 years; 8 women, 11 men) who underwent LBBAP (13 LBBAP only and 6 LBBAP + LV pacing), and 14 consecutive patients (mean age: 75 years; 8 women, 6 men) who underwent RVP. Demographic data, QRS durations, and echocardiographic parameters were compared before and after the procedures. Results: LBBAP substantially shortened the QRS duration and improved LV dyssynchrony echocardiographic parameters. However, RVP was not significantly associated with prolonged QRS duration and worse LV dyssynchronization. LBBAP improved cardiac contractility in selected patients. We did not find adverse effects of LBBAP on patients with preserved systolic function, possibly due to the limited number of patients and follow-up time. However, two of the 11 patients with preserved systolic function at baseline who underwent conventional RVP developed heart failure after implantation. Conclusions: In our experience, LBBAP improves LBBB-related ventricular dyssynchrony. However, LBBAP requires greater skill, and doubts remain about lead extraction. LBBAP may be an option for patients with LBBB when performed by an experienced operator, however further studies are needed to verify our findings.

The application of augmented reality in plastic surgery training and education: A narrative review.

Continuing problems with fewer training opportunities and a greater awareness of patient safety have led to a constant search for an alternative technique to bridge the existing theory-practice gap in plastic surgery training and education. The current COVID-19 epidemic has aggravated the situation, making it urgent to implement breakthrough technological initiatives currently underway to improve surgical education. The cutting edge of technological development, augmented reality (AR), has already been applied in numerous facets of plastic surgery training, and it is capable of realizing the aims of education and training in this field. In this article, we will take a look at some of the most important ways that AR is now being used in plastic surgery education and training, as well as offer an exciting glimpse into the potential future of this field thanks to technological advancements.

Effect of extended field-of-view approaches on the accuracy of stopping power ratio estimation for single-energy computed tomography simulators.

BACKGROUND: Extended field-of-view (eFOV) methods have been proposed to generate larger demonstration FOVs for computed tomography (CT) simulators with a limited scanning FOV (sFOV) size in order to ensure accurate dose calculation and patient collision avoidance. Although the efficacy of these strategies has been evaluated for photon applications, the effect of stopping power ratio (SPR) estimation on proton therapy has not been studied. This study investigated the effect of an eFOV approach on the accuracy of SPR to water estimation in homogeneous and heterogeneous phantoms. MATERIALS AND METHODS: To simulate patient geometries, tissue-equivalent material (TEM) and customized extension phantoms were used. The TEM phantom supported various rod arrangements through predefined holes. Images were reconstructed to three FOV sizes using a commercial eFOV technique. A single-energy CT stoichiometric method was used to generate Hounsfield unit (HU) to SPR (HU-to-SPR) conversion curves for each FOV. To investigate the effect of rod location in the sFOV and eFOV regions, eight TEM rods were placed at off-center distances in the homogeneous phantom and scanned individually. Similarly, 16 TEM rods were placed in the heterogeneous TEM phantom and scanned simultaneously. RESULTS: The conversion curves derived from the sFOV and eFOV data were identical. The average SPR differences of soft-tissue, bone, and lung materials for rods placed at various off-center locations were 3.3%, 4.8%, and 39.6%, respectively. In the heterogeneous phantom, the difference was within 1.0% in the absence of extension. However, in the presence of extension, the difference increased to 2.8% for all rods, except for lung materials, whose difference was 4.8%. CONCLUSIONS: When an eFOV method is used, the SPR variation in phantoms considerably increases for all TEM rods, especially for lung TEM rods. This phenomenon may substantially increase the uncertainty of HU-to-SPR conversion. Therefore, image reconstruction with a standard FOV size is recommended.

Early prediction of delirium upon intensive care unit admission: Model development, validation, and deployment.

STUDY OBJECTIVE: To develop, validate, and deploy models for predicting delirium in critically ill adult patients as early as upon intensive care unit (ICU) admission. DESIGN: Retrospective cohort study. SETTING: Single university teaching hospital in Taipei, Taiwan. PATIENTS: 6238 critically ill patients from August 2020 to August 2021. MEASUREMENTS: Data were extracted, pre-processed, and split into training and testing datasets based on the time period. Eligible variables included demographic characteristics, Glasgow Coma Scale, vital signs parameters, treatments, and laboratory data. The predicted outcome was delirium, defined as any positive result (a score ≥ 4) of the Intensive Care Delirium Screening Checklist that was assessed by primary care nurses in each 8-h shift within 48 h after ICU admission. We trained models to predict delirium upon ICU admission (ADM) and at 24 h (24H) after ICU admission by using logistic regression (LR), gradient boosted trees (GBT), and deep learning (DL) algorithms and compared the models' performance. MAIN RESULTS: Eight features were extracted from the eligible features to train the ADM models, including age, body mass index, medical history of dementia, postoperative intensive monitoring, elective surgery, pre-ICU hospital stays, and GCS score and initial respiratory rate upon ICU admission. In the ADM testing dataset, the incidence of ICU delirium occurred within 24 h and 48 h was 32.9% and 36.2%, respectively. The area under the receiver operating characteristic curve (AUROC) (0.858, 95% CI 0.835-0.879) and area under the precision-recall curve (AUPRC) (0.814, 95% CI 0.780-0.844) for the ADM GBT model were the highest. The Brier scores of the ADM LR, GBT, and DL models were 0.149, 0.140, and 0.145, respectively. The AUROC (0.931, 95% CI 0.911-0.949) was the highest for the 24H DL model and the AUPRC (0.842, 95% CI 0.792-0.886) was the highest for the 24H LR model. CONCLUSION: Our early prediction models based on data obtained upon ICU admission could achieve good performance in predicting delirium occurred within 48 h after ICU admission. Our 24-h models can improve delirium prediction for patients discharged >1 day after ICU admission.

Prevalence and prognostic implications of hypertensive response to exercise in patients with hypertrophic cardiomyopathy.

Objective: Hypertensive response to exercise (HRE) is observed in patients with hypertrophic cardiomyopathy (HCM) with normal resting blood pressure (BP). However, the prevalence or prognostic implications of HRE in HCM remain unclear. Methods: In this study, normotensive HCM subjects were enrolled. HRE was defined as systolic BP > 210 mmHg in men or >190 mmHg in women, or diastolic BP > 90 mmHg, or an increase in diastolic BP > 10 mmHg during treadmill exercise. All participants were followed for subsequent development of hypertension, atrial fibrillation (AF), heart failure (HF), sustained ventricular tachycardia/fibrillation (VT/VF), and all-cause death. Six hundred and eighty HCM patients were screened. Results: 347 patients had baseline hypertension, and 333 patients were baseline normotensive. 132 (40%) of the 333 patients had HRE. HRE was associated with female sex, lower body mass index and milder left ventricular outflow tract obstruction. Exercise duration and metabolic equivalents were similar between patients with or without HRE, but the HRE group had higher peak heart rate (HR), better chronotropic response and more rapid HR recovery. Conversely, non-HRE patients were more likely to exhibit chronotropic incompetence and hypotensive response to exercise. After a mean follow-up of 3.4 years, patients with and without HRE had similar risks of progression to hypertension, AF, HF, sustained VT/VF or death. Conclusion: HRE is common in normotensive HCM patients during exercise. HRE did not carry higher risks of future hypertension or cardiovascular adverse outcomes. Conversely, the absence of HRE was associated with chronotropic incompetence and hypotensive response to exercise.

Supramolecular hydrogel for programmable delivery of therapeutics to cancer multidrug resistance.

Multidrug resistance (MDR) has been considered as a major adversary in oncologic chemotherapy. To simultaneously overcome drug resistance and inhibit tumor growth, it is essential to develop a drug delivery system that can carry and release multiple therapeutic agents with spatiotemporal control. In this study, we developed a hydrogel containing an enzyme-cleavable peptide motif, with a network structure formed by 4-armed polyethylene glycol (PEG) crosslinked by complementary nucleic acid sequences. Hydrogen bond formation between nucleobase pairing allows the hydrogel to be injectable, and the peptide motif grants deliberate control over hydrogel degradation and the responsive drug release. Moreover, MDR-targeted siRNAs are complexed with stearyl-octaarginine (STR-R8), while doxorubicin (Dox) is intercalated with DNA and nanoclay structures in this hydrogel to enhance therapeutic efficacy and overcome MDR. The results show a successful configuration of a hydrogel network with in situ gelation property, injectability, and degradability in the presence of tumor-associated enzyme, MMP-2. The synergistic effect by combining MDR-targeted siRNAs and Dox manifests with the enhanced anti-cancer effect on drug resistant breast cancer cells in both in vitro and in vivo tumor models. We suggest that with the tailor-designed hydrogel system, multidrug resistance in tumor cells can be significantly inhibited by the co-delivery of multiple therapeutics with spatial-temporal control release.

Lower Risk of Burn Injury in Children and Adolescents with Autism Spectrum Disorder: A Nationwide Population-Based Study.

Little research has examined burn injury in the pediatric population with autism spectrum disorder (ASD). We used data from Taiwan's National Health Insurance Research Database to identify 15,844 participants aged <18 years with ASD and 130,860 participants without ASD. Our results revealed that the hazard ratios differed across three age ranges. The ASD group had a lower risk of burn injury than the non-ASD group when they were less than 6 years of age, a higher risk from 6 years to 12 years of age, and no difference when they were older than 12 years of age. More research is required to study the characteristics and causes of burn injury in the pediatric population with ASD.

Blockade of the pentraxin 3/CD44 interaction attenuates lung injury-induced fibrosis.

BACKGROUND: Fibrosing interstitial lung diseases (fILD) are potentially fatal with limited therapeutic options and no effective strategies to reverse fibrogenesis. Myofibroblasts are chief effector cells in fibrosis that excessively deposit collagen in the pulmonary interstitium and lead to progressive impairment of gaseous exchange. METHODS: Plasma and lung specimens from patients with fILD were applied for detecting pentraxin 3 (PTX3) abundance by ELISA and Immunohistochemistry. Masson's trichrome and Sirius red stains and hydroxyproline assay were performed for assessing collagen accumulation in the lungs of bleomycin-exposed conditional Ptx3-deficient and PTX3-neutralizing antibody (αPTX3i)-treated mice. Downstream effectors including signaling pathways and fibrotic genes were examined for assessing CD44-involved PTX3-induced fibrosis in HFL1 and primary mouse fibroblasts. RESULTS: PTX3 was upregulated in the lungs and plasma of bleomycin-exposed mice and correlated with disease severity and adverse outcomes in fILD patients. Decreased collagen accumulation, attenuation of alveolar fibrosis and fibrotic markers, and improved lung function were observed in bleomycin-exposed conditional Ptx3-deficient mice. PTX3 activates lung fibroblasts to differentiate towards migrative and highly collagen-expressing myofibroblasts. Lung fibroblasts with CD44 inactivation attenuated the PI3K-AKT1, NF-κB, and JNK signaling pathways and fibrotic markers. αPTX3i mimic-based therapeutic studies demonstrated abrogation of the migrative fibroblast phenotype and myofibroblast activation in vitro. Notably, αPTX3i inhibited lung fibrosis, reduced collagen deposition, increased mouse survival, and improved lung function in bleomycin-induced pulmonary fibrosis. CONCLUSIONS: The present study reveals new insights into the involvement of the PTX3/CD44 axis in fibrosis and suggests PTX3 as a promising therapeutic target in fILD patients.

Pre-germinated brown rice alleviates non-alcoholic fatty liver disease induced by high fructose and high fat intake in rat.

In past researches, we had been proved the action mechanism of pre-germinated brown rice (PGBR) to treat metabolic syndrome and diabetes mellitus. This study was to investigate the protective effect of PGBR in high fructose and high fat-induced non-alcoholic fatty liver disease (NAFLD) in rodents. WKY rats were divided into: Control group was fed normal drinking water and diet; FLD group was fed 10% high-fructose-water (HFW) and high-fat-diet (HFD); PGBR group was given HFW, and HFD mixed PGBR. After four weeks, the body, hepatic and cardiac weight gains of FLD group had significant increases than that of Control group. The enhanced blood pressure and heart rate, hypertriglyceridemia, hyperuricemia, and higher liver function index (GPT levels) were observed; meanwhile, the IL-6 and TNF-α levels of serum, and TG level of liver were also elevated in FLD group. The related protein expressions of lipid synthesis, inflammation, cardiac fibrosis, and hypertrophy were deteriorated by HFW/HFD. However, in treatment group, PGBR decreased all above influenced parameters, additionally GOT; and related protein expressions. PGBR treated HFW/HFD-induced NAFLD and cardiac complications might be via improving lipid homeostasis, and inhibiting inflammation. Together, PGBR could be used as a healthy food for controlling NAFLD and its' cardiac dysfunction.

Mechanistic Studies and In Vivo Efficacy of an Oxadiazole-Containing Antibiotic.

Methicillin-resistant Staphylococcus aureus (MRSA) infections are still difficult to treat, despite the availability of many FDA-approved antibiotics. Thus, new compound scaffolds are still needed to treat MRSA. The oxadiazole-containing compound, HSGN-94, has been shown to reduce lipoteichoic acid (LTA) in S. aureus, but the mechanism that accounts for LTA biosynthesis inhibition remains uncharacterized. Herein, we report the elucidation of the mechanism by which HSGN-94 inhibits LTA biosynthesis via utilization of global proteomics, activity-based protein profiling, and lipid analysis via multiple reaction monitoring (MRM). Our data suggest that HSGN-94 inhibits LTA biosynthesis via direct binding to PgcA and downregulation of PgsA. We further show that HSGN-94 reduces the MRSA load in skin infection (mouse) and decreases pro-inflammatory cytokines in MRSA-infected wounds. Collectively, HSGN-94 merits further consideration as a potential drug for staphylococcal infections.