Clinical features and lymphocyte immunophenotyping analysis in primary immunodeficiency patients with non-transplant lymphoproliferative disorders.

Lymphoproliferative disorders (LPD) comprise a heterogeneous group and are originally classified into the "Disease of immune dysregulation" category. Of 96 Taiwanese patients during 2003-2022, 31 (median 66, range 0.03-675 months) developed LPD, mainly including palpable lymphadenopathy (in 10 patients), intestinal lymphadenopathy associated with refractory inflammatory bowel disease (IBD in 8) and hepatosplenomegaly (in 7) during long-term follow-up (median 144, range 3-252 months). They distributed in the categories of antibody deficiency (2 CVID, 2 TTC37, PIK3CD, PIK3R1 and AICDA each), phagocyte (4 CYBB, 1 STAT1 and 1 IFNRG1), immune dysregulation (2 FOXP3, 2 XIAP and 2 HLH), combined immunodeficiencies (2 IL2RG; CD40L, ZAP70 and unknown each), syndromic features (2 STAT3-LOF, 1 WAS and 1 ATM) and three with anti-IFN-γ autoantibodies. An increased senescent (CD8 + CD57+) and CD21-low, disturbed transitional B (CD38 + IgM++), plasmablast B (CD38++IgM-), memory B (CD19 + CD27+) and TEMRA (CD27-IgD-) components were often observed in cross-sectional immunophenotyping and trended to develop LPD.

A preliminary study of the effectiveness of video visitation on depression and stress in mothers with preterm infants during the pandemic.

BACKGROUND AND PURPOSE: Parents of preterm infants experience anxiety and stress in the neonatal intensive care unit (NICU). Visitation restrictions due to COVID-19 have increased maternal pressure and limited bonding opportunities. Little research exists in Taiwan on using video conferencing as a solution. This study investigates depression and stress levels in mothers of preterm infants and evaluates the effectiveness of video visitation during NICU restrictions. METHODS: This study adopts a cross-sectional design and a qualitative survey. Mothers of premature infants were recruited and they participated in the study. Interventions for video visits were scheduled on the third day of admission to the NICU (T1) and during the second week of the study (T2). After each video visit, participants completed an online survey. The study's online survey used structured questionnaires including demographics, the Edinburgh Postnatal Depression Scale (EPDS) and the Parental Stress Scale (PSS): Infant Hospitalization (IH). RESULTS: A total of 51 mothers of preterm infants participated in the study. During the T1 and T2 periods, single mothers with lower educational levels and those aged below 30 experienced depression and high levels of stress. Lower birth weight and gestational age were associated with maternal depression. Video visitation intervention led to a significant decrease in depression scores (EPDS, T1: 11.3 ± 5.5 vs. T2: 10.1 ± 5.2, p = 0.039). Positive correlations were observed between EPDS and PSS: IH scores (p < 0 .005). CONCLUSION: Video visitation intervention can reduce maternal depression in mothers with preterm infants. Since it is practical, video visitation may be applied even after the pandemic.

[Improving the Rate of Palliative Care Completion in NICU Nurses].

BACKGROUND: Critically ill neonates receive care in the neonatal intensive care unit (NICU). Unfortunately, some neonates pass away in the NICU. Providing comprehensive neonatal palliative care and hospice services is crucial in supporting parents through the loss of their offspring. In our NICU, we identified that only 74.5% of nurses are able to properly recognize the need for palliative care and only 55% are able to implement the necessary procedures. PURPOSE: A project was designed and implemented to enhance the ability of nursing staff to recognize the need for and properly implement palliative care to improve the quality of this care in the NICU. RESOLUTIONS: We organized an on-the-job education and training program within our NICU with the goals of heightening awareness among nursing staff. In addition, a specialist palliative care operation flow chart, process preparation checklist, and palliative-care-related tools were created to facilitate the care process. RESULTS: After program implementation, among nursing staff in our NICU, the palliative care recognition accuracy rate rose to 100% (from 74.5%) and the implementation rate rose to 94.8% (from 55%). The quality of provided neonatal palliative care and hospice services was significantly improved. CONCLUSIONS: The developed program was shown to significantly improve nursing staff recognition and implementation of neonatal palliative care in our NICU. This experience provides a reference for improving palliative care quality and for helping families effectively manage end-of-life challenges.

Enhancing nurses' perceptions of having a place to reduce turnover intentions.

AIM: To investigate whether education, tenure, being an advanced practice nurse, skill level, and time pressure impact perceptions of "having a place" and, further, turnover intentions. BACKGROUND: Nursing shortages persist worldwide. Nurses' turnover intentions are negatively related to their perceptions of "having a place" (i.e., the feeling that the nursing workplace is their territory). However, the sources of nurses' perceptions of the perception of "having a place" remain unknown. METHODS: Our research employed a cross-sectional and correlational design. This research was conducted at a large-scale hospital in northern Taiwan from December 2021 to January 2022. We used personnel data pertaining to 430 nurses as well as scales for time pressure, "having a place" and turnover intentions to assess nurses' intention to leave their place of employment. The inclusion criteria focused on full-time nurses who worked for the hospital under investigation. Most of our participants were women. The STROBE statement was used as the EQUATOR checklist (supplemental file). RESULTS: "Having a place" was positively related to educational level, tenure, and skill level, while being an advanced practice nurse was negatively associated with perceptions of "having a place," which in turn were negatively related to turnover intention among nurses. CONCLUSION: Our study is the first to examine the antecedents of nurses' perceptions of "having a place," which include education, tenure, and skill level. IMPLICATIONS FOR NURSING POLICY: Nursing policymakers could encourage nurses to pursue higher degrees and update their nursing skills while instilling perceptions of "having a place" in nurses with a brief tenure and advanced practice nurses.

Gypenoside XIII regulates lipid metabolism in HepG2 hepatocytes and ameliorates nonalcoholic steatohepatitis in mice.

Gypenoside XIII is isolated from Gynostemma pentaphyllum (Thunb.) Makino. In mice, G. pentaphyllum extract and gypenoside LXXV have been shown to improve non-alcoholic steatohepatitis (NASH). This study investigated whether gypenoside XIII can regulate lipid accumulation in fatty liver cells or attenuate NASH in mice. We used HepG2 hepatocytes to establish a fatty liver cell model using 0.5 mM oleic acid. Fatty liver cells were treated with different concentrations of gypenoside XIII to evaluate the molecular mechanisms of lipid metabolism. In addition, a methionine/choline-deficient diet induced NASH in C57BL/6 mice, which were given 10 mg/kg gypenoside XIII by intraperitoneal injection. In fatty liver cells, gypenoside XIII effectively suppressed lipid accumulation and lipid peroxidation. Furthermore, gypenoside XIII significantly increased SIRT1 and AMPK phosphorylation to decrease acetyl-CoA carboxylase phosphorylation, reducing fatty acid synthesis activity. Gypenoside XIII also decreased lipogenesis by suppressing sterol regulatory element-binding protein 1c and fatty acid synthase production. Gypenoside XIII also increased lipolysis and fatty acid ß-oxidation by promoting adipose triglyceride lipase and carnitine palmitoyltransferase 1, respectively. In an animal model of NASH, gypenoside XIII effectively decreased the lipid vacuole size and number and reduced liver fibrosis and inflammation. These findings suggest that gypenoside XIII can regulate lipid metabolism in fatty liver cells and improve liver fibrosis in NASH mice. Therefore, gypenoside XIII has potential as a novel agent for the treatment of NASH.

The association between human milk fatty acid composition in mothers with an elevated body mass index and infant growth changes.

BACKGROUND & AIMS: Few studies have investigated alternations in human milk polyunsaturated fatty acid (PUFA) composition in the context of maternal obesity and its effects on infant growth trajectories. This study explored whether maternal weight status and breastfeeding type influence human milk FA composition and infant anthropometry during the first six months of life. METHODS: Mother-infant dyads were enrolled from the Prediction of Allergies in Taiwanese Children birth cohort study. Data concerning maternal pre-pregnancy weight, infants' breastfeeding practices, and anthropometric data were obtained regularly. We identified and compared between the composition of 30 FAs in the colostrum and 2-month milk, respectively, in obese/overweight (OB/OW) and normal-weight (NW) mothers. Multiple linear regression analyses were performed to determine the association between PUFA composition at different lactation stages and infant anthropometric parameter changes and to identify the independent variables for body mass index (BMI) z-scores by six months of age. RESULTS: We included 338 mother-infant dyads (OB/OW mothers, 16.9 %). OB/OW mothers exhibited lower total n-3 PUFAs (P = 0.035), higher ratios of arachidonic acid (C20:4n-6)/eicosapentaenoic acid (C20:5n-3) + docosahexaenoic acid (C22:6n-3), and n-6/n-3 PUFA in colostrum (P = 0.037 and 0.011, respectively), and their offspring had higher body weight and BMI z-scores. Nevertheless, no PUFA composition or n-6/n-3 PUFA ratios in colostrum and 2-month milk were associated with anthropometric parameter changes by age 6 months. Infant birth weight z-scores were independently associated with BMI outcomes at age 6 months (adjusted ß = 0.16, 95 % confidence interval (0.05-0.35), P = 0.010) CONCLUSION: Neither n-3 nor n-6 PUFA profiles nor n-6/n-3 PUFA ratios at different lactation stages were found to be associated with anthropometric changes by age 6 months, suggesting that human milk PUFA composition may not be an important determinant of early infant growth trajectories.

Adeno-Associated Viral Vector-Delivered Pannexin-1 Mimetic Peptide Alleviates Airway Inflammation in an Allergen-Sensitized Mouse Model.

Asthma is a chronic inflammatory disease around the world. Extracellular adenosine triphosphate works as a dangerous signal in responding to cellular stress, irritation, or inflammation. It has also been reported its association with the pathogenicity in asthma, with increased level in lungs of asthmatics. Pannexin-1 is one of the routes that contributes to the release of adenosine triphosphate form intracellular to extracellular. The aim of this study was to apply pannexin-1 peptide antagonist 10Panx1 into adeno-associated viral (AAV) vectors on ovalbumin (OVA)-induced asthmatic mouse model. The results demonstrated that this treatment was able to reduce the adenosine triphosphate level in bronchoalveolar lavage fluid and downregulate the major relevant to the symptom of asthma attack, airway hyperresponsiveness to methacholine. The histological data also gave a positive support with decreased tissue remodeling and mucus deposition. Other asthmatic related features, including eosinophilic inflammation and OVA-specific T helper type 2 responses, were also decreased by the treatment. Beyond the index of inflammation, the proportion of effector and regulatory T cells was examined to survey the potential mechanism behind. The data provided a slightly downregulated pattern in lung GATA3+ CD4 T cells. However, an upregulated population of CD25+FoxP3+ CD4 T cells was seen in spleens. These data suggested that exogeneous expression of 10Panx1 peptide was potential to alleviated asthmatic airway inflammation, and this therapeutic effect might be from 10Panx1-mediated disruption of T cell activation or differentiation. Collectively, AAV vector-mediated 10Panx1 expression could be a naval therapy option to develop.

Introduction of Egg White and Yolk to Infant Diets and Early Childhood Atopic Dermatitis.

This study investigated whether the introduction of allergenic foods in infancy is associated with atopic dermatitis (AD) in early childhood. Information regarding parental allergic histories, the introduction of six possible allergenic foods (fruits, egg white, egg yolk, fish, shellfish, and peanuts), and physician-diagnosed AD was obtained using age-specific questionnaires (0-2 years). Immunoglobulin E, specific to 20 food allergens, was also quantified at 12 months of age. Logistic regression analyses were used to determine the association between individual food introduction and the outcomes of food sensitization and AD. We found AD development by 2 years of age was significantly related to a parental history of allergy (adjusted odds ratio (aOR) = 1.29) and not being introduced to egg white and yolk during infancy (aORs = 2.27 and 1.97, respectively). Stratified analyses revealed that the introduction of both egg white and yolk was negatively associated with AD by 2 years of age, especially for those children where both parents had allergic diseases (aOR = 0.10). In summary, the introduction of egg white and yolk to an infant's diet may be a modifiable factor in reducing the risk of physician-diagnosed AD by 2 years of age, which may be particularly important for infants where both parents have allergies.

[Improve the Completion Rate of ECMO Placement Assistance for Nurses in the NICU].

BACKGROUND & PROBLEMS: The extracorporeal membrane oxygenation (ECMO) system can provide cardiopulmonary support to and reduce the mortality rate in severely ill newborns. According to our investigation, completion rate of the care process among staff nurses was only 63.5% in our ward. We assumed that the reasons for the above problems included: lack of care awareness, unfamiliarity with the ECMO operation process, inadequate instruments preparation, improper ECMO pipeline fixation, lack of designated space in the unit for placing ECMO supplies, lack of specialty care guidelines, lack of a regular inspection system, and lack of regular on-the-job education. PURPOSE: Improve awareness related to assisting ECMO placement among nurses in the neonatal intensive care unit and the completeness of care. RESOLUTIONS: 1. Create a care process guidebook describing the procedures for ECMO system placement in newborns to help nurse accomplish proper placement. 2. Establish the ECMO system consumables checklist and install an ECMO system-specialized toolbox to reduce the preparation time and smooth the process. 3. Regularly organize comprehensive nurse training and develop performance indicators to enhance ECMO system placement awareness and skills. RESULTS: The cognitive accuracy rate for the assisted placement of ECMO among nurses in the neonatal intensive care unit increased from 51.9% before improvement to 89.9% afterward. Also, the complete care rate of ECMO placement increased from 63.5% before improvement to 100% afterward. CONCLUSIONS: This project effectively improved the accuracy rate of nurses involved in assisting with ECMO placement, made the ECMO system placement process easier to implement, improved the care process completion rate, and improved newborn care quality.

Contribution of genetic variants associated with primary immunodeficiencies to childhood-onset systemic lupus erythematous.

BACKGROUND: A dysregulated immune response is a hallmark of autoimmune disorders. Evidence suggests that systemic autoimmune diseases and primary immunodeficiency disorders (PIDs) may be similar diseases with different clinical phenotypes. OBJECTIVE: This study aimed to investigate the burden of PID-associated genetic variants in patients with childhood-onset systemic lupus erythematosus (cSLE). METHODS: We enrolled 118 cSLE patients regularly followed at Chang Gung Memorial Hospital. Targeted next-generation sequencing identified PID genetic variants in patients versus 1475 unrelated healthy individuals, which were further filtered by allelic frequency and various functional scores. Customized immune assays tested the functions of the identified variants. RESULTS: On filtration, 36 patients (30.5%) harbored rare variants in PID-associated genes predicted to be damaging. One homozygous TREX1 (c.294dupA) mutation and 4 heterozygous variants with possible dominant PID traits, including BCL11B (c.G1040T), NFKB1 (c.T695G), and NFKB2 (c.G1210A, c.G1651A), were discovered. With recessive traits, variants were found across all PID types; one fifth involved phagocyte number or function defects. Predicted pathogenic PID variants were more predominant in those with a family history of lupus, regardless of infection susceptibility. Moreover, mutation loads were greater among cSLE patients than controls despite sex or age at disease onset. While greater mutation loads were observed among cSLE patients with peripubertal disease onset, no significant differences in sex or phenotype were noted among cSLE patients. CONCLUSION: cSLE is mostly not monogenic. Gene-specific analysis and mutation load investigations suggested that rare and predicted damaging variants in PID-related genes can potentially contribute to cSLE susceptibility.

Association between Serum Zinc and Toll-like-Receptor- Related Innate Immunity and Infectious Diseases in Well-Nourished Children with a Low Prevalence of Zinc Deficiency: A Prospective Cohort Study.

Existing reports focus on zinc-associated immunity and infection in malnourished children; however, whether zinc also plays an important role in the immune homeostasis of the non-zinc-deficient population remained unknown. This study aimed to investigate the association between zinc status and toll-like receptor (TLR)-related innate immunity and infectious outcome in well-nourished children. A total of 961 blood samples were collected from 1 through 5 years of age. Serum zinc was analyzed, and mononuclear cells isolated to assess TNF-α, IL-6, and IL-10 production by ELISA after stimulation with TLR ligands. Childhood infections were analyzed as binary outcomes with logistic regression. The prevalence of zinc deficiency was 1.4-9.6% throughout the first 5 years. There was significant association between zinc and TLR-stimulated cytokine responses. Higher serum zinc was associated with decreased risk of ever having pneumonia (aOR: 0.94; 95% CI: 0.90, 0.99) at 3 years, and enterocolitis (aOR: 0.96; 95% CI: 0.93, 0.99) at 5 years. Serum zinc was lower in children who have had pneumonia before 3 years of age (72.6 ± 9 vs. 81.9 ± 13 µg/dL), and enterocolitis before 5 years (89.3 ± 12 vs. 95.5 ± 13 µg/dL). We emphasize the importance of maintaining optimal serum zinc in the young population.

The explorations of the awareness, contemplation, self-Efficacy, and readiness of advance care planning, and its predictors in Taiwanese patients while receiving hemodialysis treatment.

BACKGROUND: End-stage renal disease (ESRD) is a major chronic illness worldwide, and Taiwan reports one of the highest incidence rates of ESRD with 529 cases per million population (pmp). A number of patients with ESRD patients might require lifelong hemodialysis (HD) or peritoneal dialyses (PD). Due to the progression of dialysis, patients are likely to experience other chronic comorbidities, anxiety and depression, frequent hospitalizations, and higher rates of mortality compared to patients with other types of chronic illnesses. As a result, dialysis patients are prone to experience advance care planning (ACP) needs, such as whether they withdraw from receiving dialysis while approaching their end-of-life (EOL). Yet, existing studies have shown that dialysis patients seldom receive timely consultation regarding ACP and there are limited studies examining ACP amongst Taiwan HD patients. PURPOSE: The purpose of this study was to examine ACP awareness, contemplation, self-efficacy and readiness; and factors influencing ACP readiness. DESIGN: This cross-sectional descriptive study with convenience sampling was conducted in the out-patient HD unit at a regional teaching hospital in southern Taiwan. A total of 143 ESRD patients undergoing HD treatments were recruited. A 55-item ACP engagement survey containing the subscales of awareness, contemplation, self-efficacy, and readiness was employed. The data were analyzed with t-tests, one-way ANOVAs, Pearson's correlations and multiple regressions. RESULTS: The results of our investigation revealed that approximately half of the participants (n = 67, 46.9%) were not informed of ACP. Although they reported considering their EOL, medical decisions and desired care, they demonstrated significantly low self-efficacy in discussing ACP (t= -5.272, p < 0.001). HD duration influenced all four ACP subscales; religious beliefs significantly influenced ACP-self-efficacy and readiness; and marital status, education, and primary decision-maker status significantly influenced ACP-readiness. The predictors of ACP-readiness were high self-efficacy and being the primary decision-maker (Adjusted R2 61%). CONCLUSION: Most of the HD patients in this study had low ACP-awareness, contemplation, self-efficacy, and readiness, and most had not completed any ACP-related advance directives (AD). Healthcare professionals should proactively provide HD patients with ACP-related information and answer patients' and medical decision-makers' questions in a timely manner, thereby improving the quality of EOL care.

The Post-Traumatic Growth of Primary Caregivers of Patients after Liver Transplantation.

Liver transplantation is a very important surgery. In many cases, it involves two loved ones (receiver and donor in the same family) and causes stress and feelings of burden in family caregivers. The purpose of this study was to investigate post-traumatic growth in primary caregivers of liver transplant patients. A cross-sectional research design was adopted to recruit 84 participants. The Perceived Stress Scale, Short-Form Coping Strategies Scale, and Post-traumatic Growth Scale were used. The results revealed that the total score of perceived stress of the main caregivers of liver transplantation was 27.27 ± 6.63; problem-oriented coping and emotion-oriented coping were used as the main coping strategies, and the traumatic growth score was 42.01 ± 13.84. All three variables were significant predictors of post-traumatic growth (F = 13.71, p < 0.05), explaining 38% of the total variance. This study can help nurses understand the post-traumatic growth status and related factors of the main caregivers of liver transplant patients. It can also help caregivers understand their own perceived pressure and then take relevant care measures to reduce the degree of physical and mental load and achieve a balanced state.

Perilla Fruit Water Extract Attenuates Inflammatory Responses and Alleviates Neutrophil Recruitment via MAPK/JNK-AP-1/c-Fos Signaling Pathway in ARDS Animal Model.

Airway respiratory distress syndrome (ARDS) is usually caused by a severe pulmonary infection. However, there is currently no effective treatment for ARDS. Traditional Chinese medicine (TCM) has been shown to effectively treat inflammatory lung diseases, but a clear mechanism of action of TCM is not available. Perilla fruit water extract (PFWE) has been used to treat cough, excessive mucus production, and some pulmonary diseases. Thus, we propose that PFWE may be able to reduce lung inflammation and neutrophil infiltration in a lipopolysaccharide (LPS)-stimulated murine model. C57BL/6 mice were stimulated with LPS (10 µg/mouse) by intratracheal (IT) injection and treated with three doses of PFWE (2, 5, and 8 g/kg) by intraperitoneal (IP) injections. To investigate possible mechanisms, A549 cells were treated with PFWE and stimulated with LPS. Our results showed that PFWE decreased airway resistance, neutrophil infiltration, vessel permeability, and interleukin (IL)-6 and chemokine (C-C motif) ligand 2 (CCL2/MCP-1) expressions in vivo. In addition, the PFWE inhibited the expression of IL-6, CCL2/MCP-1, chemokine (CXC motif) ligand 1 (CXCL1/GROα), and IL-8 in vitro. Moreover, PFWE also inhibited the MAPK/JNK-AP-1/c-Fos signaling pathway in A549 cells. In conclusion, we demonstrated that PFWE attenuated pro-inflammatory cytokine and chemokine levels and downregulated neutrophil recruitment through the MAPK/JNK-AP-1/c-Fos pathway. Thus, PFWE can be a potential drug to assist the treatment of ARDS.

[Reducing the Incidence of Feeding Intolerance in Premature Infants in the Neonatal Intensive Care Unit].

BACKGROUND ≥ PROBLEMS: Nutrition is very important for premature infants. Our recent research showed that the accuracy of recognition related to tube feeding was 74.8%, and the completeness of tube feeding was 74.3%. After analyzing this situation, the reasons found to be significantly associated with the low rates of tube-feeding recognition accuracy and completion included: inconsistent treatment of gastric residual by nurses in the neonatal intensive care unit (NICU), lack of sufficient assessment tools in the NICU, out-of-date specialist care guidelines, and lack of a regular inspection system. PURPOSE: Our aim was to improve tube-feeding-related recognition accuracy and completion to reduce the incidence of feeding intolerance. RESOLUTIONS: The intervention included developing a guideline manual for feeding procedures and making a gastric residual color card as a clinical-care reference. Holding on-the-job training and monitoring the quality of nursing care can reduce the incidence of feeding intolerance in preterm. RESULTS: The accuracy of tube-feeding recognition increased from 74.8% to 93.7%. The completion of tube feeding increased from 74.3% to 95.5%. The incidence of feeding intolerance in premature infants decreased from 71.8% to 39.0%. CONCLUSIONS: The results and process of this project provides a reference for improving the clinical care model for preterm infants in the NICU and for improving the enteral nutrition of preterm infants. The implementation of this project may improve the quality of nursing care and enable preterm infants to receive safer and more-complete care.

Sophoraflavanone G from Sophora flavescens Ameliorates Allergic Airway Inflammation by Suppressing Th2 Response and Oxidative Stress in a Murine Asthma Model.

Sophoraflavanone G (SG), isolated from Sophora flavescens, has anti-inflammatory and anti-tumor bioactive properties. We previously showed that SG promotes apoptosis in human breast cancer cells and leukemia cells and reduces the inflammatory response in lipopolysaccharide-stimulated macrophages. We investigated whether SG attenuates airway hyper-responsiveness (AHR) and airway inflammation in asthmatic mice. We also assessed its effects on the anti-inflammatory response in human tracheal epithelial cells. Female BALB/c mice were sensitized with ovalbumin, and asthmatic mice were treated with SG by intraperitoneal injection. We also exposed human bronchial epithelial BEAS-2B cells to different concentrations of SG to evaluate its effects on inflammatory cytokine levels. SG treatment significantly reduced AHR, eosinophil infiltration, goblet cell hyperplasia, and airway inflammation in the lungs of asthmatic mice. In the lungs of ovalbumin-sensitized mice, SG significantly promoted superoxide dismutase and glutathione expression and attenuated malondialdehyde levels. SG also suppressed levels of Th2 cytokines and chemokines in lung and bronchoalveolar lavage samples. In addition, we confirmed that SG decreased pro-inflammatory cytokine, chemokine, and eotaxin expression in inflammatory BEAS-2B cells. Taken together, our data demonstrate that SG shows potential as an immunomodulator that can improve asthma symptoms by decreasing airway-inflammation-related oxidative stress.

Adeno-Associated Virus-Mediated Interleukin-12 Gene Expression Alleviates Lung Inflammation and Type 2 T-Helper-Responses in Ovalbumin-Sensitized Asthmatic Mice.

High levels of allergen exposure increase the prevalence of asthma in developed countries. The asthmatic type 2 T-helper (Th2) response is characterized with high eosinophil infiltration, elevated Th2 cytokines, and immunoglobulin (Ig) E secretion resulting in local or systemic inflammation. However, the treatment with palliative Th2 inhibitor drugs cannot completely control asthma and that is why the development of novel approaches is still important. Based on type 1 T-helper (Th1) and Th2 immune homeostasis, the enhanced Th1 immune response has high potential to alleviate Th2 immune response. Thus, we aimed to overexpress single chain IL-12 (scIL-12) through recombinant adeno-associated virus (rAAV) vector (as rAAV-IL-12) and test the efficacy in an ovalbumin (OVA)-induced asthmatic murine model. We firstly demonstrated the bioactivity of exogenous scIL-12. The expression of exogenous scIL-12 was also detected in the lungs of rAAV-IL-12 transduced mice. The data demonstrated that overexpression of exogenous scIL-12 significantly suppressed total number of cells and eosinophil infiltration, as well as the mucus secretion in rAAV-IL-12-treated mice. The decreased OVA-specific IgE in bronchoalveolar lavage fluid and gene expression of Th2-cytokines or C-C motif ligand (CCL) 11 (also eotaxin-1) in lung were observed. In addition, the production of cytokines in the supernatants of OVA-stimulated splenocytes were suppressed with rAAV-IL-12 treatment. Thus, scIL-12 expression by rAAV vector was able to modulate Th2 activity and has the potential to be developed as a feasible strategy in modulating allergic diseases.

Acacetin Protects against Non-Alcoholic Fatty Liver Disease by Regulating Lipid Accumulation and Inflammation in Mice.

We previously demonstrated that acacetin reduces adipogenesis in adipocytes, and decreases lipid accumulation in visceral adipocyte tissue. Here we investigated whether acacetin regulated the mechanisms of lipogenesis and inflammation in non-alcoholic fatty liver disease (NAFLD) in obese mice. Male C57BL/6 mice were fed a high-fat diet (HFD), and then administered acacetin by intraperitoneal injection. Acacetin reduced body weight and liver weight in obese mice. Acacetin-treated obese mice exhibited decreased lipid accumulation, increased glycogen accumulation, and improved hepatocyte steatosis. Acacetin regulated triglycerides and total cholesterol in the liver and serum. Acacetin decreased low-density lipoprotein and leptin concentrations, but increased high-density lipoprotein and adiponectin levels in obese mice. Acacetin effectively weakened the gene expressions of transcription factors related to lipogenesis, and promoted the expressions of genes related to lipolysis and fatty acid ß-oxidation in liver. Acacetin also reduced expressions of inflammation-related cytokines in the serum and liver. Oleic acid induced lipid accumulation in murine FL83B hepatocytes, and the effects of acacetin treatment indicated that acacetin may regulate lipid metabolism through the AMPK pathway. Acacetin may protect against hepatic steatosis by modulating inflammation and AMPK expression.

Increased fecal human beta-defensin-2 expression in preterm infants is associated with allergic disease development in early childhood.

Background: This study aimed to investigate whether fecal human beta-defensins (HBD)-2 and eosinophil cationic protein (ECP) expression in preterm infants are associated with allergic disease development by age 2 years. Methods: Preterm infants' stool samples were collected at the age of 6 and 12 months postnatally. Information regarding medication exposure histories (antibiotics, antipyretics, probiotics) and physician-diagnosed allergic diseases was obtained using age-specific questionnaires and medical records. We compared the 6-month and 12-month fecal HBD-2 and ECP concentrations between the medication exposure and non-exposure group, respectively, and between children who developed allergic diseases and those who did not by 2 years of age. Univariate and multivariable logistic regression analyses were performed to investigate independent variables related to physician-diagnosed allergic diseases by 2 years of age. Results: Seventy-four preterm infants (gestational age, 31-36 weeks) were included. Fecal HBD-2 levels were significantly increased at 12 months of age among children who developed allergic diseases compared to those who did not (37.18 ± 11.80 ng/g vs. 8.56 ± 4.33 ng/g, P = 0.011). This association was more apparent among allergic children given antibiotics (50.23 ± 16.15 ng/g vs. 9.75 ± 7.16 ng/g, P = 0.008) or antipyretics (46.12 ± 14.22 ng/g vs. 10.82 ± 6.81 ng/g, P = 0.018) during the first year, whereas among allergic children who were previously not exposed to antibiotics or antipyretics, the differences were not significant. Results of the multivariable logistic regression analysis indicated that HBD-2 concentration in 12-month stools was an independent indicator associated with physician-diagnosed allergic diseases by 2 years of age (adjusted odds ratio: 1.03 [95% confidence interval: 1.00-1.05], P = 0.036). Our data revealed a lack of association between fecal ECP and allergic diseases. Conclusions: We found that preterm infants who expressed high fecal HBD-2 at 12 months of age were associated with physician-diagnosed allergic diseases by the age of 2 years. Further studies are needed to determine the role of fecal HBD-2 in the development of allergic diseases.

Comorbidities of systemic lupus erythematosus prior to and following diagnosis in different age-at-onset groups.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a female-dominated autoimmune disease that can occur at any age and has a diverse course. The clinical manifestation of this disease can vary depending on the patient's age at onset. The aim of this study was to characterise the comorbidities at the time of SLE diagnosis and after in different age groups. METHODS: A total 1042 incident cases of SLE with a Catastrophic Illness Card in 2005 and 10,420 age- and sex-matched controls from the general population registered in the National Health Insurance Research Database in Taiwan were enrolled in the study. The risk of comorbidities before (adjusted odds ratio, [aOR]) and after (adjusted hazard ratio, [aHR]) of SLE was analysed. The burden of these SLE-associated comorbidities was weight by the Charlson comorbidity index (CCI). We used the cumulative incidence to evaluate the impact of comorbidities on different age onset groups. RESULTS: In this study, musculoskeletal diseases had the highest positive association (aOR, 5.29; 95% confidence interval [CI]: 4.25-6.57) prior to the diagnosis of SLE and they were also the most common developing incident comorbidity after the diagnosis (HR, 13.7; 95% CI: 11.91-15.77). It only took less than 1 year for 50% of the late-onset SLE patients to develop any increase in CCI score. The developing comorbidities attributed to 16.3% all-cause mortality and they had the greatest impact on late-onset SLE patients, with 33.3% cumulative incidence to all-cause mortality. There is no difference in the incidence of infectious diseases across different age groups. The herpes zoster infection had the greatest cumulative incidence among the category of infection diseases in child-onset SLE patients. CONCLUSION: SLE patients had increased risks of multiple pre-existing comorbidities at diagnosis. The developed comorbidity after diagnosis could contribute to all-cause mortality. The herpes zoster infection is primarily an issue in child-onset SLE patients.