Preparation and properties of thermoplastic starch under the synergism of ultrasonic and elongational rheology.

Thermoplastic starch, as an eco-friendly alternative to petroleum-based plastics, possesses numerous advantages, including cost-effectiveness, complete biodegradability, and renewable sourcing. Nevertheless, the plasticizer dispersion and starch plasticization efficiency are poor via the processing method dominate by shear deformation. Thus, the aim of this study is proposing a new approach combining ultrasonic treatment and elongational rheology to prepare thermoplastic starch and evaluate its properties. This innovative approach facilitated the production of thermoplastic starch with glycerol as the plasticizer at varying rotor speeds. Furthermore, this study was carried out by using a self-developed ultrasonic-assisted vane mixer (UVM) based on elongational flow. The samples were analyzed using FTIR, WAXD, polarized optical microscope, dynamic rheometer, universal testing machine and thermogravimetric analysis. FTIR and dynamic rheological analysis showed that elongational rheology and ultrasonics stimulate hydrogen bond formation between starch and glycerol, elevating starch thermoplasticity. Tensile tests and thermogravimetric analysis highlighted that high-intensity elongational field improved the mechanical properties and thermal stability of the thermoplastic starch. Additionally, the incorporation of ultrasonic treatment yielded further improvements, yielding remarkable tensile strength (6.09 MPa) and elongation at break (139.3 %). This synergistic interplay between ultrasonics and elongational rheology holds immense potential for advancing thermoplastic starch manufacturing.

A Chinese patent medicine's long-term efficacy on non-dialysis patients with CKD stages 3-5: a retrospective cohort study.

Background: Chinese patent medicine is commonly used in China as an important treatment mechanism to thwart the progression of chronic kidney disease (CKD) stages 3-5, among which Niaoduqing granules are a representative Chinese patent medicine; however, its long-term efficacy on CKD prognosis remains unclear. Methods: Patients were grouped according to Niaoduqing granule prescription duration (non-Niaoduqing granule (non-NDQ) group vs Niaoduqing granule (NDQ) group). Serum creatinine (SCr) variation was compared using a generalized linear mixed model (GLMM). Multivariate Cox regression models were constructed, adjusting for confounding factors, to explore the risk of composite outcomes (receiving renal replacement therapy (RRT) or having an estimated glomerular filtration rate (eGFR)<5 mL/min/1.73 m2, ≥50% decline in the eGFR from the baseline, and doubling of SCr) in individuals consuming Niaoduqing granules. Results: A total of 1,271 patients were included, with a median follow-up duration of 29.71 (12.10, 56.07) months. The mean SCr Z-scores for the non-NDQ group and NDQ group were -0.175 and 0.153, respectively, at baseline (p = 0.015). The coefficients of the NDQ group from visit 1 to visit 5 were -0.207 (95% CI: -0.346, -0.068, p = 0.004), -0.214 (95% CI: 0.389, -0.039, p = 0.017), -0.324 (95% CI: 0.538, -0.109, p = 0.003), -0.502 (95% CI: 0.761, -0.243, p = 0.000), and -0.252 (95% CI: 0.569, 0.065, p = 0.119), respectively. The survival probability was significantly higher in the NDQ group (p = 0.0039). Taking Niaoduqing granules was a significant protective factor for thwarting disease progression (model 1: HR 0.654 (95% CI 0.489-0.875, p = 0.004); model 2: HR 0.646 (95% CI 0.476, 0.877, p = 0.005); and model 3: HR 0.602 (95% CI 0.442, 0.820, p = 0.001)). Conclusion: The long-term use of Niaoduqing granules improved SCr variation and lowered the risk of CKD progression by 39.8%.

Clinical risk factors for preterm birth and evaluating maternal psychology in the postpartum period.

BACKGROUND: Although the specific pathogenesis of preterm birth (PTB) has not been thoroughly clarified, it is known to be related to various factors, such as pregnancy complications, maternal socioeconomic factors, lifestyle habits, reproductive history, environmental and psychological factors, prenatal care, and nutritional status. PTB has serious implications for newborns and families and is associated with high mortality and complications. Therefore, the prediction of PTB risk can facilitate early intervention and reduce its resultant adverse consequences. AIM: To analyze the risk factors for PTB to establish a PTB risk prediction model and to assess postpartum anxiety and depression in mothers. METHODS: A retrospective analysis of 648 consecutive parturients who delivered at Shenzhen Bao'an District Songgang People's Hospital between January 2019 and January 2022 was performed. According to the diagnostic criteria for premature infants, the parturients were divided into a PTB group (n = 60) and a full-term (FT) group (n = 588). Puerperae were assessed by the Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS), based on which the mothers with anxiety and depression symptoms were screened for further analysis. The factors affecting PTB were analyzed by univariate analysis, and the related risk factors were identified by logistic regression. RESULTS: According to univariate analysis, the PTB group was older than the FT group, with a smaller weight change and greater proportions of women who underwent artificial insemination and had gestational diabetes mellitus (P < 0.05). In addition, greater proportions of women with reproductive tract infections and greater white blood cell (WBC) counts (P < 0.05), shorter cervical lengths in the second trimester and lower neutrophil percentages (P < 0.001) were detected in the PTB group than in the FT group. The PTB group exhibited higher postpartum SAS and SDS scores than did the FT group (P < 0.0001), with a higher number of mothers experiencing anxiety and depression (P < 0.001). Multivariate logistic regression analysis revealed that a greater maternal weight change, the presence of gestational diabetes mellitus, a shorter cervical length in the second trimester, a greater WBC count, and the presence of maternal anxiety and depression were risk factors for PTB (P < 0.01). Moreover, the risk score of the FT group was lower than that of the PTB group, and the area under the curve of the risk score for predicting PTB was greater than 0.9. CONCLUSION: This study highlights the complex interplay between postpartum anxiety and PTB, where maternal anxiety may be a potential risk factor for PTB, with PTB potentially increasing the incidence of postpartum anxiety in mothers. In addition, a greater maternal weight change, the presence of gestational diabetes mellitus, a shorter cervical length, a greater WBC count, and postpartum anxiety and depression were identified as risk factors for PTB.

A Senescence-Associated Secretory Phenotype of Bone Marrow Mesenchymal Stem Cells Inhibits the Viability of Breast Cancer Cells.

Breast cancer, the most prevalent malignancy in women, often progresses to bone metastases, especially in older individuals. Dormancy, a critical aspect of bone-metastasized breast cancer cells (BCCs), enables them to evade treatment and recur. This dormant state is regulated by bone marrow mesenchymal stem cells (BMMSCs) through the secretion of various factors, including those associated with senescence. However, the specific mechanisms by which BMMSCs induce dormancy in BCCs remain unclear. To address this gap, a bone-specific senescence-accelerated murine model, SAMP6, was utilized to minimize confounding systemic age-related factors. Confirming senescence-accelerated osteoporosis, distinct BMMSC phenotypes were observed in SAMP6 mice compared to SAMR1 counterparts. Notably, SAMP6-BMMSCs exhibited premature senescence primarily due to telomerase activity loss and activation of the p21 signaling pathway. Furthermore, the effects of conditioned medium (CM) derived from SAMP6-BMMSCs versus SAMR1-BMMSCs on BCC proliferation were examined. Intriguingly, only CM from SAMP6-BMMSCs inhibited BCC proliferation by upregulating p21 expression in both MCF-7 and MDA-MB-231 cells. These findings suggest that the senescence-associated secretory phenotype (SASP) of BMMSCs suppresses BCC viability by inducing p21, a pivotal cell cycle inhibitor and tumor suppressor. This highlights a heightened susceptibility of BCCs to dormancy in a senescent microenvironment, potentially contributing to the increased incidence of breast cancer bone metastasis and recurrence observed with aging.

The experiences and needs of people with dysvascular lower extremity amputations: a qualitative systematic review and meta-synthesis.

PURPOSE: The aim of this review is to synthesise the experiences and needs of people who had undergone dysvascular lower extremity amputations. Given the increasing global prevalence of vascular diseases like diabetes mellitus and peripheral arterial disease, the risk of requiring an amputation remains high. MATERIALS AND METHODS: This systematic review follows the PRISMA and ENTREQ reporting guidelines. Seven databases were searched for qualitative studies from January 2011 to October 2023. In total 6435 studies were obtained, where 1146 were duplicates and 5271 studies failed to meet the eligibility criteria. The remaining 18 studies were synthesised using Sandelowski and Barroso's approach and appraised using the CASP checklist. RESULTS: Four themes emerged from the meta-synthesis: (1) making the decision to amputate, (2) difficulties in the physical adaptation to limb loss, (3) psychosocial consequences of living with an amputation, and (4) regaining control and building hope. CONCLUSIONS: Having dysvascular lower extremity amputations is a complicated experience as not only was the pre-amputation pain relieved, but a new set of physical, emotional and social challenges would surface after the amputation. These synthesised findings serve as a platform to explore the factors behind the various experiences faced by these people and how healthcare professionals can help them in their adjustment.

Dysvascular lower extremity amputations can affect the physical and mental well-being of people who have experienced them.Healthcare professionals (HCPs) are encouraged to individualise care that meets the physical and emotional needs of patients.Sufficient time and information should be provided before the operation for these people to be better prepared for the changes following the amputation.Physical support by HCPs should include physical rehabilitation, checking on the wound healing and managing any existing co-morbidities.Emotional support can be given through additional referral to medical social workers or psychologists and the involvement of support groups.

Region-specific sympatho-adrenergic regulation of specialized vasculature in bone homeostasis and regeneration.

Type H vessels couple angiogenesis with osteogenesis, while sympathetic cues regulate vascular and skeletal function. The crosstalk between sympathetic nerves and type H vessels in bone remains unclear. Here, we first identify close spatial connections between sympathetic nerves and type H vessels in bone, particularly in metaphysis. Sympathoexcitation, mimicked by isoproterenol (ISO) injection, reduces type H vessels and bone mass. Conversely, beta-2-adrenergic receptor (ADRB2) deficiency maintains type H vessels and bone mass in the physiological condition. In vitro experiments reveal indirect sympathetic modulation of angiogenesis via paracrine effects of mesenchymal stem cells (MSCs), which alter the transcription of multiple angiogenic genes in endothelial cells (ECs). Furthermore, Notch signaling in ECs underlies sympathoexcitation-regulated type H vessel formation, impacting osteogenesis and bone mass. Finally, propranolol (PRO) inhibits beta-adrenergic activity and protects type H vessels and bone mass against estrogen deficiency. These findings unravel the specialized neurovascular coupling in bone homeostasis and regeneration.

Mesenchymal Stem Cell Aggregation-Released Extracellular Vesicles Induce CD31+ EMCN+ Vessels in Skin Regeneration and Improve Diabetic Wound Healing.

The blood vessel system is essential for skin homeostasis and regeneration. While the heterogeneity of vascular endothelial cells has been emergingly revealed, whether a regeneration-relevant vessel subtype exists in skin remains unknown. Herein, a specialized vasculature in skin featured by simultaneous CD31 and EMCN expression contributing to the regeneration process is identified, the decline of which functionally underlies the impaired angiogenesis of diabetic nonhealing wounds. Moreover, enlightened by the developmental process that mesenchymal condensation induces angiogenesis, it is demonstrated that mesenchymal stem/stromal cell aggregates (CAs) provide an efficacious therapy to enhance regrowth of CD31+ EMCN+ vessels in diabetic wounds, which is surprisingly suppressed by pharmacological inhibition of extracellular vesicle (EV) release. It is further shown that CAs promote secretion of angiogenic protein-enriched EVs by proteomic analysis, which directly exert high efficacy in boosting CD31+ EMCN+ vessels and treating nonhealing diabetic wounds. These results add to the current knowledge on skin vasculature and help establish feasible strategies to benefit wound healing under diabetic condition.

Effectiveness of aromatherapy on anxiety and sleep quality among adult patients admitted into intensive care units: A systematic review.

PURPOSE: This review aims to evaluate the effectiveness of aromatherapy on anxiety and sleep quality among adult patients admitted to an intensive care unit. MATERIALS AND METHODS: A systematic search for published and unpublished studies across nine databases and sources were conducted. Randomised Controlled Trials and Controlled Clinical Trials, which assessed the effectiveness of aromatherapy on anxiety and sleep quality among intensive care unit patients, were included in this review. Only studies that used aromatherapy as a single intervention were included. Narrative synthesis was conducted across all outcomes due to high heterogeneity across studies. RESULTS: A total of 26 studies involving 2176 participants across six countries were included in this review. Most studies had an overall high risk of bias. Publication bias was detected in the studies. Findings have shown that aromatherapy may be effective in reducing anxiety based on the low GRADE certainty of evidence, and improving sleep quality based on the very low GRADE certainty of evidence. Inconsistencies in findings were also observed. CONCLUSION: Aromatherapy might be beneficial on anxiety and sleep quality among intensive care unit patients, however, the level of evidence is very low, based on the low quality of studies. Considerations can be made to incorporate aromatherapy into existing interventions that improve anxiety and sleep quality in the intensive care unit. Due to inconsistencies in findings, further research can be done to investigate and strengthen these evidence. IMPLICATION FOR CLINICAL PRACTICE: This review has demonstrated that aromatherapy may have benefits on anxiety and sleep quality. Despite uncertain evidence, aromatherapy may still be considered as a complementary or alternative option to improve anxiety and sleep quality among intensive care patients as it is relatively safe, cost-effective and easy to implement (Buckle, 2014). However, proper training by a professional clinical aromatherapist is needed to ensure there is screening of patients for suitability, proper technique for administering aromatherapy, safe handling of essential oils and monitoring for adverse events (Farrar & Farrar, 2020).

Sphingosine-1-phosphate induces myocyte autophagy after myocardial infarction through mTOR inhibition.

Sphingosine-1-phosphate (S1P)/S1P receptor 1 signaling exerts cardioprotective effects including inhibition of myocyte apoptosis. However, little is known about the effect of S1P treatment on myocyte autophagy after myocardial infarction (MI). In the present study, we tested the hypothesis that S1P induces myocyte autophagy through inhibition of the mammalian target of rapamycin (mTOR), leading to improvement of left ventricular (LV) function after MI. Sprague-Dawley rats underwent MI or sham operation. The animals were randomized to receive S1P (50 µg/kg/day, i.p.) or placebo for one week. H9C2 cardiomyocytes cultured in serum- and glucose-deficient medium were treated with or without S1P for 3 h. MI rats exhibited an increase in LV end-diastolic dimension (EDD) and decreases in LV fractional shortening (FS) and the maximal rate of LV pressure rise (+dP/dt). S1P treatment attenuated the increase in LV EDD and decreases in LV FS and +dP/dt. In the MI placebo group, the LC3 II/I ratio, a marker of autophagy, was increased, and increased further by S1P treatment. S1P also enhanced the autophagy-related proteins Atg4b and Atg5 after MI. Similarly, in cultured cardiomyocytes, autophagy was increased under glucose and serum deprivation, and increased further by S1P treatment. The effect of S1P on myocyte autophagy was associated with mTOR inhibition after MI or in cultured cardiomyocytes under glucose and serum deprivation. S1P treatment prevents LV remodeling, enhances myocyte autophagy and inhibits mTOR activity after MI. These findings suggest that S1P treatment induces myocyte autophagy through mTOR inhibition, leading to the attenuation of LV dysfunction after MI.

Apocynin prevents reduced myocardial nerve growth factor, contributing to amelioration of myocardial apoptosis and failure.

Reduced nerve growth factor (NGF) is associated with cardiac sympathetic nerve denervation in heart failure (HF) which is characterized by increased oxidative stress. Apocynin is considered an antioxidant agent which inhibits NADPH oxidase activity and improves reactive oxygen species scavenging. However, it is unclear whether apocynin prevents reduced myocardial NGF, leading to improvement of cardiac function in HF. In this study, we tested the hypothesis that apocynin prevents reduced myocardial NGF, contributing to amelioration of myocardial apoptosis and failure. Rabbits with myocardial infarction (MI) or sham operation were randomly assigned to receive apocynin or placebo for 4 weeks. MI rabbits exhibited left ventricular (LV) dysfunction, and elevation in oxidative stress, as evidenced by a decreased reduced-to-oxidized glutathione ratio and an increased 4-hydroxynonenal expression, and reduction in NGF and NGF receptor tyrosine kinase A (TrKA) expression in the remote non-infarcted myocardium. Apocynin treatment ameliorated LV dysfunction, reduced oxidative stress, prevented decreases in NGF and TrKA expression and reduced cardiomyocyte apoptosis after MI. In cultured H9C2 cardiomyocytes, hypoxia or hydrogen peroxide decreased NGF expression, and apocynin normalized hypoxia-induced reduction of NGF. Recombinant NGF attenuated hypoxia-induced apoptosis. Apocynin prevented hypoxia-induced apoptosis, and the suppressive effect of apocynin on apoptosis was abolished by NGF receptor TrKA inhibitor K252a. We concluded that apocynin prevented reduced myocardial NGF, leading to attenuation of cardiomyocyte apoptosis and LV remodelling and dysfunction in HF after MI. These findings suggest that strategies to prevent NGF reduction by inhibition of oxidative stress may be of value in amelioration of LV dysfunction in HF.

Exploring prior diseases associated with pancreatic cancer.

Background Pancreatic cancer (PC) is among the most deadly forms of cancer; however, the risk factors of PC have yet to be sufficiently identified. In the present study, we sought to screen all prior diseases associated with PC incidence concurrently and construct pathways for the diseases. Materials and methods This total population-based case-control study used data collected from Taiwan's National Health Insurance Research Database for the period covering 1997-2013. The case group included 3726 patients newly diagnosed with PC, who were precisely matched to 3726 controls based on gender, age, residence, and insurance premiums. Stepwise multivariate logistic regression was used to screen previous diseases in windows of 1, 2 …, 9 years prior to the first diagnosis of PC. Path analysis was used to construct the pathways between relevant prior diseases and PC. Results Within 1 year prior to PC diagnosis, a total of 11 diseases were significantly correlated with PC, included 9 positive and 2 negative associations. Path analysis identified diabetes, pancreatitis as diseases with direct positive pathways to PC incidence, and dementia with direct negative pathways. Conclusions It appears that diabetes, peptic ulcer, and digestive conditions were the prior diseases associated with PC incidence.

Gender differences in acute toxicity, toxicokinetic and tissue distribution of amphotericin B liposomes in rats.

Amphotericin B (AmB), an effective polyene drug with broad spectrum antifungal activity, is used for serious fungal infections. Liposomal amphotericin B (LAmB) is a lipid dosage form, which has a significantly improved toxicity profile compared with conventional amphotericin B deoxycholate (DAmB). This study focused on verifying the gender differences in the acute toxicity of LAmB and further exploring its causes. Acute toxicity study of LAmB and DAmB were performed in rats, and toxicity responses and mortality of different sexes were observed and recorded. Concentrations of AmB in rat plasma and tissues were determined by a fully validated UPLC-MS/MS assay. The results demonstrated that LAmB showed significant gender differences in acute toxicity, with more severe toxic symptoms and higher mortality for female rats at different doses, but the same differences were not observed for DAmB under the same condition. To explore the cause of differences, toxicokinetic and tissue distribution studies were performed and the results showed that female animals had higher drug exposure, longer half-life and lower plasma clearance compared to male rats, and the drug was mostly distributed in the liver and kidneys, in which female rats displayed a significant higher concentration than that of male rats.

ROP18-Mediated Transcriptional Reprogramming of HEK293T Cell Reveals New Roles of ROP18 in the Interplay Between Toxoplasma gondii and the Host Cell.

Toxoplasma gondii secretes a number of virulence-related effector proteins, such as the rhoptry protein 18 (ROP18). To further broaden our understanding of the molecular functions of ROP18, we examined the transcriptional response of human embryonic kidney cells (HEK293T) to ROP18 of type I T. gondii RH strain. Using RNA-sequencing, we compared the transcriptome of ROP18-expressing HEK293T cells to control HEK293T cells. Our analysis revealed that ROP18 altered the expression of 750 genes (467 upregulated genes and 283 downregulated genes) in HEK293T cells. Gene ontology (GO) and pathway enrichment analyses showed that differentially expressed genes (DEGs) were significantly enriched in extracellular matrix- and immune-related GO terms and pathways. KEGG pathway enrichment analysis revealed that DEGs were involved in several disease-related pathways, such as nervous system diseases and eye disease. ROP18 significantly increased the alternative splicing pattern "retained intron" and altered the expression of 144 transcription factors (TFs). These results provide new insight into how ROP18 may influence biological processes in the host cells via altering the expression of genes, TFs, and pathways. More in vitro and in vivo studies are required to substantiate these findings.

iTRAQ-based Quantitative Proteomics Analysis Identifies Host Pathways Modulated during Toxoplasma gondii Infection in Swine.

Toxoplasma gondii is a leading cause of foodborne illness and consumption of undercooked pig meat is a major risk factor for acquiring toxoplasmosis, which causes a substantial burden on society. Here, we used isobaric tags for relative and absolute quantification (iTRAQ) labelling coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify cellular proteins and pathways altered during T. gondii infection in pigs. We also used parallel reaction monitoring-based LC-MS/MS to verify the levels of protein expression of infected spleens and mesenteric lymph nodes (MLNs). At 6 days post-infection (dpi), 156, 391, 170, 292, and 200 differentially expressed proteins (DEPs) were detected in the brain, liver, lung, MLNs and spleen, respectively. At 18 dpi, 339, 351, 483, 388, and 303 DEPs were detected in the brain, liver, lung, MLNs and spleen, respectively. Although proteins involved in immune responses were upregulated in all infected tissues, protein expression signature in infected livers was dominated by downregulation of the metabolic processes. By weighted gene co-expression network analysis, we could further show that all proteins were clustered into 25 co-expression modules and that the pink module significantly correlated with the infection status. We also identified 163 potential anti-T. gondii proteins (PATPs) and provided evidence that two PATPs (HSP70.2 and PDIA3) can reduce T. gondii burden in porcine macrophages in vitro. This comprehensive proteomics analysis reveals new facets in the pathogenesis of T. gondii infection and identifies key proteins that may contribute to the pig's defense against this infection.

Transcriptional changes in Toxoplasma gondii in response to treatment with monensin.

BACKGROUND: Infection with the apicomplexan protozoan parasite T. gondii can cause severe and potentially fatal cerebral and ocular disease, especially in immunocompromised individuals. The anticoccidial ionophore drug monensin has been shown to have anti-Toxoplasma gondii properties. However, the comprehensive molecular mechanisms that underlie the effect of monensin on T. gondii are still largely unknown. We hypothesized that analysis of T. gondii transcriptional changes induced by monensin treatment can reveal new aspects of the mechanism of action of monensin against T. gondii. METHODS: Porcine kidney (PK)-15 cells were infected with tachyzoites of T. gondii RH strain. Three hours post-infection, PK-15 cells were treated with 0.1 µM monensin, while control cells were treated with medium only. PK-15 cells containing intracellular tachyzoites were harvested at 6 and 24 h post-treatment, and the transcriptomic profiles of T. gondii-infected PK-15 cells were examined using high-throughput RNA sequencing (RNA-seq). Quantitative real-time PCR was used to verify the expression of 15 differentially expressed genes (DEGs) identified by RNA-seq analysis. RESULTS: A total of 4868 downregulated genes and three upregulated genes were identified in monensin-treated T. gondii, indicating that most of T. gondii genes were suppressed by monensin. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of T. gondii DEGs showed that T. gondii metabolic and cellular pathways were significantly downregulated. Spliceosome, ribosome, and protein processing in endoplasmic reticulum were the top three most significantly enriched pathways out of the 30 highly enriched pathways detected in T. gondii. This result suggests that monensin, via down-regulation of protein biosynthesis in T. gondii, can limit the parasite growth and proliferation. CONCLUSIONS: Our findings provide a comprehensive insight into T. gondii genes and pathways with altered expression following monensin treatment. These data can be further explored to achieve better understanding of the specific mechanism of action of monensin against T. gondii.

The NADPH oxidase inhibitor apocynin improves cardiac sympathetic nerve terminal innervation and function in heart failure.

NEW FINDINGS: What is the central question of this study? Does NADPH oxidase activation mediate cardiac sympathetic nerve denervation and dysfunction in heart failure. What is the main findings and its importance? Cardiac sympathetic nerve terminal density and function were reduced in heart failure after myocardial infarction in rabbits. The NADPH oxidase inhibitor apocynin prevented the reduction in cardiac sympathetic nerve terminal density and function in heart failure. This suggest that NADPH oxidase activation mediates cardiac sympathetic nerve terminal abnormalities in heart failure. NADPH oxidase may be a potential therapeutic target for cardiac sympathetic denervation and dysfunction in heart failure. ABSTRACT: Congestive heart failure (CHF) is characterized by cardiac sympathetic nerve terminal abnormalities, as evidenced by decreased noradrenaline transporter (NAT) density and cardiac catecholaminergic and tyrosine hydroxylase (TH) profiles. These alterations are associated with increased reactive oxygen species (ROS). NADPH oxidase is a major source of ROS in CHF. In this study, we tested the hypothesis that NADPH oxidase activation mediates cardiac sympathetic nerve terminal abnormalities in CHF. CHF was produced by myocardial infarction (MI) in rabbits. Rabbits with MI or a sham operation were randomized to orally receive an NADPH oxidase inhibitor, apocynin (6 mg kg-1  day-1 ), or placebo for 30 days. MI rabbits exhibited left ventricular dilatation, systolic dysfunction, and increases in NADPH oxidase activity and 4-hydroxynonenal expression in the remote non-infarcted myocardium, all of which were prevented by treatment with apocynin. Cardiac catecholaminergic histofluorescence profiles and immunostained TH and PGP9.5 expression were decreased, and the decreases were ameliorated by apocynin treatment. NAT, TH and PGP9.5 protein and mRNA expression were reduced and the reduction was mitigated by apocynin treatment. The effects of apocynin were confirmed by utilizing the NADPH oxidase inhibitor diphenyleneiodonium in a separate experiment. In conclusion, the NADPH oxidase inhibitor apocynin attenuated increased myocardial oxidative stress and decreased cardiac sympathetic nerve terminals in CHF after MI in rabbits. These findings suggest that the activation of NADPH oxidase mediates cardiac sympathetic nerve terminal abnormalities in CHF, and the inhibition of NADPH oxidase may be beneficial for the treatment of heart failure.

The Multitasking Fasciola gigantica Cathepsin B Interferes With Various Functions of Goat Peripheral Blood Mononuclear Cells in vitro.

Cathepsin B, a lysosomal cysteine protease, is thought to be involved in the pathogenesis of Fasciola gigantica infection, but its exact role remains unclear. In the present study, a recombinant F. gigantica cathepsin B (rFgCatB) protein was expressed in the methylotrophic yeast Pichia pastoris. Western blot analysis confirmed the reactivity of the purified rFgCatB protein to serum from F. gigantica-infected goats. The effects of serial concentrations (10, 20, 40, 80, and 160 µg/ml) of rFgCatB on various functions of goat peripheral blood mononuclear cells (PBMCs) were examined. We demonstrated that rFgCatB protein can specifically bind to the surface of PBMCs. In addition, rFgCatB increased the expression of cytokines (IL-2, IL-4, IL-10, IL-17, TGF-ß, and IFN-γ), and increased nitric oxide production and cell apoptosis, but reduced cell viability. These data show that rFgCatB can influence cellular and immunological functions of goat PBMCs. Further characterization of the posttranslational modification and assessment of rFgCatB in immunogenicity studies is warranted.

Global Transcriptome Profiling of Multiple Porcine Organs Reveals Toxoplasma gondii-Induced Transcriptional Landscapes.

We characterized the porcine tissue transcriptional landscapes that follow Toxoplasma gondii infection. RNAs were isolated from liver, spleen, cerebral cortex, lung, and mesenteric lymph nodes (MLNs) of T. gondii-infected and uninfected (control) pigs at days 6 and 18 postinfection, and were analyzed using next-generation sequencing (RNA-seq). T. gondii altered the expression of 178, 476, 199, 201, and 362 transcripts at 6 dpi and 217, 223, 347, 119, and 161 at 18 dpi in the infected brain, liver, lung, MLNs and spleen, respectively. The differentially expressed transcripts (DETs) were grouped into five expression patterns and 10 sub-clusters. Gene Ontology enrichment and pathway analysis revealed that immune-related genes dominated the overall transcriptomic signature and that metabolic processes, such as steroid biosynthesis, and metabolism of lipid and carboxylic acid, were downregulated in infected tissues. Co-expression network analysis identified transcriptional modules associated with host immune response to infection. These findings not only show how T. gondii infection alters porcine transcriptome in a tissue-specific manner, but also offer a gateway for testing new hypotheses regarding human response to T. gondii infection.

Toxoplasma gondii ROP17 inhibits the innate immune response of HEK293T cells to promote its survival.

Toxoplasma gondii secretes a group of rhoptry-secreted kinases (ROPs), which play significant roles in promoting intracellular infection. T. gondii rhoptry organelle protein 17 (ROP17) is one of these important effector proteins. However, its role in modulating host cell response during infection remains poorly understood. Here, we reveal that ROP17 (genotype I) induces significant changes in the expression genes and transcription factors of host cells. HEK293T cells were transfected with PCMV-N-HA-ROP17 plasmid or empty control PCMV-N-HA plasmid. Transcriptomic analysis revealed 3138 differentially expressed genes (DEGs) in PCMV-N-HA-ROP17-transfected HEK293T cells, including 1456 upregulated, 1682 downregulated DEGs. Also, 715 of the DEGs were transcription factors (TFs), including 423 downregulated TFs and 292 upregulated TFs. Most differentially expressed TFs, whether belong to signal transduction, cancer-related pathways or immune-related pathways, were downregulated in ROP17-expressing cells. ROP17 also decreased alternative splicing events in host cells, presumably via alteration of the expression of genes involved in the alternative splicing pathway. Taken together, our findings suggest a novel strategy whereby T. gondii ROP17 manipulates various cellular processes, including immune response through reprogramming host gene expression to promote its own colonization and survival in the infected host cells.

Sphingobacterium athyrii sp. nov., a cellulose- and xylan-degrading bacterium isolated from a decaying fern (Athyrium wallichianum Ching).

Assessment of the bacterial diversity associated with a decaying fern, Athyrium wallichianum Ching, revealed the presence of a novel bacterial strain named M46T. It was Gram-stain-negative, rod-shaped, non-motile and aerobic with cellulose and xylan degradation abilities. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain M46T was affiliated to the genus Sphingobacterium, exhibiting the highest sequence similarity of 97.9 % to Sphingobacterium ginsenosidimutans THG 07T, Sphingobacterium canadense CR11T and Sphingobacterium detergens6.2 ST. Multilocus sequence analysis (MLSA) based on concatenated sequences of the rpoB, cpn60 and 16S rRNA genes showed that strain M46T clustered together with S. canadense CR11T. The genome of strain M46T had a G+C content of 40.6 mol% and chromosome of 6 853 865 bp. Average nucleotide identity (ANI) between strain M46T and S. detergens 6.2 ST and S. siyangense SY1T was 85.1 and 78.1 %, respectively. DNA-DNA relatedness values among strain M46T and other closely related Sphingobacterium species were <70 %. ANI and DNA-DNA relatedness findings strongly supported M46T as a putative novel strain of Sphingobacterium. The predominant fatty acids of strain M46T were iso-C15 : 0, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and iso-C17 : 0 3-OH, and MK-7 was the dominant isoprenoid quinone. The polar lipid profile of strain M46T contained phosphatidylethanolamine as the dominant component, while minor amounts of phosphoglycolipid, one unidentified aminophospholipid, two unidentified phospholipids and four unidentified lipids were also detected. Based on 16S rRNA gene sequence similarities, MLSA results, genomic characteristics, and phenotypic and biochemotaxonomic analyses, strain M46T is considered to represent a novel species in the genus Sphingobacterium, for which the name Sphingobacterium athyrii sp. nov. is proposed. The type strain is M46T (=CGMCC 1.13466T=JCM 32543T).