Eosinophilic granulomatosis with polyangiitis, asthma as the first symptom, and subsequent Loeffler endocarditis: A case report.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, is a rare form of anti-neutrophil cytoplasmic antibody-associated vasculitis characterized by asthma, vasculitis, and eosinophilia. CASE SUMMARY: We report an atypical case of EGPA in a 20-year-old female patient. Unlike previously reported cases of EGPA, this patient's initial symptom was asthma associated with a respiratory infection. This was followed by Loeffler endocarditis and cardiac insufficiency. She received treatment with methylprednisolone sodium succinate, low molecular weight heparin, recombinant human brain natriuretic peptide, furosemide, cefoperazone sodium/sulbactam sodium, and acyclovir. Despite prophylactic anticoagulation, she developed a large right ventricular thrombus. EGPA diagnosis was confirmed based on ancillary test results and specialty consultations. Subsequent treatment included mycophenolate mofetil. Her overall condition improved significantly after treatment, as evidenced by decreased peripheral blood eosinophils and cardiac markers. She was discharged after 17 d. Her most recent follow-up showed normal peripheral blood eosinophil levels, restored cardiac function, and a reduced cardiac mural thrombus size. CONCLUSION: This case illustrates the swift progression of EGPA and underscores the significance of early detection and immediate intervention to ensure a favorable prognosis.

Ginseng-derived panaxadiol ameliorates STZ-induced type 1 diabetes through inhibiting RORγ/IL-17A axis.

Retinoic-acid-receptor-related orphan receptor γ (RORγ) is a major transcription factor for proinflammatory IL-17A production. Here, we revealed that the RORγ deficiency protects mice from STZ-induced Type 1 diabetes (T1D) through inhibiting IL-17A production, leading to improved pancreatic islet ß cell function, thereby uncovering a potential novel therapeutic target for treating T1D. We further identified a novel RORγ inverse agonist, ginseng-derived panaxadiol, which selectively inhibits RORγ transcriptional activity with a distinct cofactor recruitment profile from known RORγ ligands. Structural and functional studies of receptor-ligand interactions reveal the molecular basis for a unique binding mode for panaxadiol in the RORγ ligand-binding pocket. Despite its inverse agonist activity, panaxadiol induced the C-terminal AF-2 helix of RORγ to adopt a canonical active conformation. Interestingly, panaxadiol ameliorates mice from STZ-induced T1D through inhibiting IL-17A production in a RORγ-dependent manner. This study demonstrates a novel regulatory function of RORγ with linkage of the IL-17A pathway in pancreatic ß cells, and provides a valuable molecule for further investigating RORγ functions in treating T1D.

Protective effects of Antrodia camphorata extract against hypoxic cell injury and ischemic stroke brain damage.

Ischemic stroke is the most prevalent stroke condition in the world resulted in either a transient ischemic attack or long-lasting neurological problems due to the interrupted or reduced blood flow to the brain. Antrodia camphorata is a well-known medicinal mushroom native to Taiwan and is familiar due to its medicinal effects. The current study investigated the protective effect of A. camphorata-alcohol extracts (AC-AE) against cobalt (II) chloride (CoCl2 )-induced oxidative stress in vitro and ischemia/reperfusion-induced brain injury in vivo. The rats were pre-treated with AC-AE for 4 weeks. Our results showed that AC-AE reduced cell damage and decreased reactive oxygen species (ROS) production in C6 and PC12 cells under CoCl2 -induced hypoxic condition. AC-AE doses (385, 770, 1,540 mg/kg/day, 4 weeks) increased nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) mRNA expressions and decreased inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA expressions in Sprague Dawley rat. Besides, it decreased stroke infarct size and increased the level of antioxidants in both brain and serum. Furthermore, it reduced the formation of malondialdehyde (MDA) after ischemia/reperfusion (I/R). Our results suggested that AC-AE exerted an effective reduction of ischemia stroke by regulating ROS production.

Surfactin-Loaded ĸ-Carrageenan Oligosaccharides Entangled Cellulose Nanofibers as a Versatile Vehicle Against Periodontal Pathogens.

PURPOSE: Periodontitis is a chronic inflammatory disease associated with microbial accumulation. The purpose of this study was to reuse the agricultural waste to produce cellulose nanofibers (CNF) and further modification of the CNF with κ-carrageenan oligosaccharides (CO) for drug delivery. In addition, this study is focused on the antimicrobial activity of surfactin-loaded CO-CNF towards periodontal pathogens. MATERIALS AND METHODS: A chemo-mechanical method was used to extract the CNF and the modification was done by using CO. The studies were further proceeded by adding different quantities of surfactin [50 mg (50 SNPs), 100 mg (100 SNPs), 200 mg (200 SNPs)] into the carrier (CO-CNF). The obtained materials were characterized, and the antimicrobial activity of surfactin-loaded CO-CNF was evaluated. RESULTS: The obtained average size of CNF and CO-CNF after ultrasonication was 263 nm and 330 nm, respectively. Microscopic studies suggested that the CNF has a short diameter with long length and CO became cross-linked to form as beads within the CNF network. The addition of CO improved the degradation temperature, crystallinity, and swelling property of CNF. The material has a controlled drug release, and the entrapment efficiency and loading capacity of the drug were 53.15 ± 2.36% and 36.72 ± 1.24%, respectively. It has antioxidant activity and inhibited the growth of periodontal pathogens such as Streptococcus mutans and Porphyromonas gingivalis by preventing the biofilm formation, reducing the metabolic activity, and promoting the oxidative stress. CONCLUSION: The study showed the successful extraction of CNF and modification with CO improved the physical parameters of the CNF. In addition, surfactin-loaded CO-CNF has potential antimicrobial activity against periodontal pathogens. The obtained biomaterial is economically valuable and has great potential for biomedical applications.

Nanoparticles of Antroquinonol-Rich Extract from Solid-State-Cultured Antrodia cinnamomea Improve Reproductive Function in Diabetic Male Rats.

PURPOSE: To characterize the nanoparticle of antroquinonol from A. cinnamomea and its ameliorative effects on the reproductive dysfunction in the diabetic male rat. MATERIAL AND METHODS: The chitosan-silicate nanoparticle was used as the carrier for the delivery of antroquinonol from solid-state-cultured A. cinnamomea extract (AC). The rats were fed with a high-fat diet and intraperitoneally injected with streptozotocin to induce diabetes. The rats were daily oral gavage by water [Diabetes (DM) and Control groups], three different doses of chitosan-silicate nanoparticle of antroquinonol from solid-state-cultured A. cinnamomea (nano-SAC, NAC): (DM+NAC1x, 4 mg/kg of body weight; DM+NAC2x, 8 mg/kg; and DM+NAC5x, 20 mg/kg), solid-state-cultured AC (DM+AC5x, 20 mg/kg), or metformin (DM+Met, 200 mg/kg) for 7 weeks. RESULTS: The nano-SAC size was 37.68±5.91 nm, the zeta potential was 4.13±0.49 mV, encapsulation efficiency was 79.29±0.77%, and loading capacity was 32.45±0.02%. The nano-SAC can improve diabetes-induced reproductive dysfunction by regulating glucose, insulin, and oxidative enzyme and by increasing the level of testosterone, follicle-stimulating hormone, luteinizing hormone, and sperm count as well as sperm mobility. In testicular histopathology, the seminiferous tubules of A. cinnamomea-supplemented diabetic rats showed similar morphology with the control group. CONCLUSION: The nanoparticle of antroquinonol from Antrodia cinnamomea can be used as an effective strategy to improve diabetes-induced testicular dysfunction.

Dietary polysaccharide-rich extract from Eucheuma cottonii modulates the inflammatory response and suppresses colonic injury on dextran sulfate sodium-induced colitis in mice.

Inflammatory bowel disease (IBD) is a known medical burden in most developed countries and a significant cause of morbidity. The IBD label includes Crohn's disease (CD) and ulcerative colitis (UC). Pharmacological and surgical intervention are the two main management approaches for IBD. Some drugs have been developed for IBD therapy, but accessibility is limited due to high costs. Furthermore, these agents have demonstrated inactivity over long-term treatment courses. Therefore, an urgent need is present for new treatment options that are safe, able to sustain clinical remission, and improve mucosal gut healing. Seaweed has received much attention in the pharmacological field owing to its various biomedical properties, including the prolongation of blood clotting time, as well as antitumor, anti-inflammation, and antioxidant effects. This study therefore aimed to examine the effects of a dietary polysaccharide-rich extract obtained from Eucheuma cottonii (EC) on a model of colitis. Colitis was induced in male BALB/c mice by the administration of 2.5% (w/v) dextran sulfate sodium (DSS) for 7 days. DSS-induced mice were treated with either one of three different doses of EC extracts (0.35, 0.70, and 1.75 g/kg body weight) or curcumin as a positive control (0.10 g/kg). Mice were sacrificed post-treatment and blood samples were collected. The disease activity index (DAI) and inflammatory cytokine levels (tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-10) were measured. After treatment for 7 days, EC extract administration protected against weight loss and decreased the colon weight per length ratio. EC extract administration also decreased pro-inflammatory cytokine expression, increased IL-10 levels, and reduced colonic damage. Therefore, a dietary polysaccharide-rich extract from E. cottonii reduced DSS-induced bowel inflammation, thereby becoming a promising candidate for the treatment of colitis.

Effect of Cistanche Tubulosa Extracts on Male Reproductive Function in Streptozotocin⁻Nicotinamide-Induced Diabetic Rats.

Diabetes is a chronic disorder characterized by hyperglycemia due to decreased levels of insulin or the inefficiency of the tissue to use it effectively. Infertility is known as a major outcome of diabetes and affects the male reproductive system by causing sperm impairment and gonadal dysfunction. Cistanche tubulosa is a parasitic plant which has the capacity to improve memory, immunity, and sexual ability, reduce impotence, and minimize constipation. This study was focused on the investigation of the anti-inflammatory and protective effects of echinacoside (ECH) in Cistanche tubulosa extract (CTE) on the male reproductive system of the diabetic rats. The antioxidant, anti-inflammatory, and protective effects of CTE were evaluated by both in vitro and in vivo methods. The in vitro results show that the ECH inhibited reactive oxygen species (ROS) production and improved StAR, CYP11A1, CYP17A1, and HSD17ß3 protein expression. The in vivo analysis was carried out with three doses of echinacoside (ECH) (80, 160, and 320 mg/kg) in CTE. In total, 0.571 mg/kg of rosiglitazone (RSG) was administered as a positive control. Diabetes was induced by streptozotocin (STZ) (65 mg/kg) and nicotinamide (230 mg/kg) in combination with a high-fat diet (45%). The in vivo studies confirmed that the ECH improved blood sugar levels, insulin resistance, leptin resistance, and lipid peroxidation. It can restore kisspeptin 1 (KiSS1), G protein-coupled receptor GPR 54, suppressor of cytokine signaling 3 (SOCS-3), and sirtuin 1 (SIRT1) messenger ribonucleic acid (mRNA) expression in the hypothalamus and recover sex hormone level. Thus, this study confirmed the antioxidant, anti-inflammatory, and steroidogenesis effects of CTE.

Modulation of Diabetes Mellitus-Induced Male Rat Reproductive Dysfunction with Micro-Nanoencapsulated Echinacea purpurea Ethanol Extract.

Diabetes mellitus is a major health problem that affects a patient's life quality throughout the world due to its worst complications. It was recognized that chronic hyperglycemia with oxidative stress was the major cause of male infertility. Echinacea purpurea ethanol extract (EE) contains phenolic acid and isobutylamides had been proven to ameliorate diabetic complications. Chitosan/silica nanoparticles are well-known in the medicinal field because of its controlled release and drug delivery properties. This study was aimed at investigating whether the EE encapsulated chitosan/silica nanoparticle (nano-EE) can enhance the amelioration of male infertility. Our results indicated that the average size of nano-EE was 218 ± 42 nm with an encapsulation efficiency of 66.9% and loading capacity of 39.9%. The reduction in oxidative stress and antioxidant activity of nano-EE was observed in LC-540 cells. In in vivo experiment, 33 mg/kg of streptozotocin (STZ) was used to induce diabetes in male Sprague-Dawley rats. Diabetic rats were treated with nano (465 mg/kg), nano-EE 1 (93mg/kg), nano-EE3 (279mg/kg), nano-EE5 (465 mg/kg), and metformin (Met) (200 mg/kg) for 7 weeks. The results show that the nano-EE5 can improve hyperglycemia, insulin resistance, and plasma fibroblast growth factor 21 (FGF 21) resistance. It was also confirmed that nano-EE5 significantly improved the testis tissue structure, increasing sperm quality and DNA integrity as well as reducing reactive oxygen species level.

Comparison of procedural, clinical and valve performance results of transcatheter aortic valve replacement in patients with bicuspid versus tricuspid aortic stenosis.

BACKGROUND: Limited date describing the procedural, clinical and valve performance results of transcatheter aortic valve replacement (TAVR) in patients with bicuspid versus tricuspid aortic stenosis (TAV). METHODS: Procedural and clinical results were defined and reported according to VARC-2 criteria. RESULTS: Consecutive 87 patients with BAV and 70 patients with TAV were included. Compared to patients with TAV, patients with BAV had similar incidence of second valve implantation (14.9% vs 12.9%, p=0.708), more than mild paravalvular leakage (PVL, 40.2% vs 31.9%, p=0.288), permanent pacemaker implantation (PPM, 24.1% vs 28.6%, p=0.53). Furthermore, the procedural and clinical results of TAVR also did not differ between patients with type 0 and type 1 (second valve implantation: 18.4% vs 11.8%, p=0.71, PVL: 38.8% vs 41.2%, p=0.83, PPM: 18.4% vs 31.6%, p=0.16). The hemodynamic outcomes were similar in patients with BAV and TAV at 1-year (maximum velocity, 2.3 vs 2.2m/s, p=0.307) and 2-year (2.3 vs 2.1m/s, p=0.184) follow-up respectively. Adjusted binary logistic regression analysis found oversizing ratio at 14.45-20.57% is at lower risk for more than mild PVL (OR, 0.069, 95% CI, 0.011-0.428, p=0.004). Moreover, the Kaplan-Meier survival analysis revealed that TAVR in type 0 BAV, type 1 BAV and TAV have comparable risk for midterm mortality (Log rank, p=0.772). CONCLUSION: TAVR in whatever type of BAV appeared to be safe and efficacy, and TAVR in BAV was associated with comparable bioprosthetic function during follow up compared to patients with TAV.

Analysis of putative ORF3 gene within porcine circovirus type 2.

Porcine circovirus type 2 (PCV2) is associated with postweaning multisystemic syndrome in pigs, whereas the ubiquitous related porcine circovirus type 1 (PCV1) is nonpathogenic. Corroborating an earlier observation in PCV2, Rep and Rep' proteins encoded by ORF1 are essential for the initiation of PCV2 replication. Cap protein encoded by ORF2 has a potential causative role in the initiation of PCV2 replication and contains a type-specific epitope. The putative ORF3 of PCV2 oriented in the opposite direction within ORF1 is unknown. In this study, ORF3-encoding protein of PCV2 was expressed in vitro as a fusion protein (GST-ORF3 protein), and monoclonal antibodies (MAbs) to the PCV2-ORF3-encoding protein were generated and biologically characterized. The mRNA transcript of ORF3 was characterized during a productive infection in PK-15 cells, and the PCV2 infectious DNA clone lacking ORF3 was constructed. GST-ORF3 protein, with an approximate molecular weight of 37.7 kDa, was obtained from the Escherichia coli transformed with the recombinant vector pGEX-4T-1-F3 after codon optimization of ORF3 DNA sequence. Four MAbs reacted strongly to the ORF3-encoding protein expressed in PK-15 cells in immunohistochemical staining. The mRNA transcript of ORF3 was confirmed in RT-PCR, Northern blot, and sequencing analyses. The progeny PCV2 virions were not revealed in the PK-15 cells transfected by the PCV2 infectious DNA clone without ORF3. These results demonstrate that the ORF3 of PCV2 can be transcribed and expressed and that ORF3-encoding protein plays a pivotal role in viral replication.

Interference of porcine circovirus type 2 ORF2 immunogenicity by ORF1 and ORF3 mixed DNA immunizations in mice.

Little is known about the influences of other porcine circovirus type 2 (PCV2) proteins on the immunogenicity of Cap protein. Here we constructed plasmids expressing the ORF1 (pORF1) and ORF3 (pORF3) of PCV2, and mixed either of them with the plasmid expressing ORF2 (pORF2) as combined DNA vaccines, to compare their immunogenicity and protective efficacy. Our data revealed that pORF1 reduced the Cap-specific CD8(+)cell frequency, and both pORF1 and pORF3 attenuated the Cap-specific Th1 and post-challenge-recall VN antibody responses induced by the pORF2 plasmid, despite successful induction of Rep and ORF3 antibodies by pORF1 and pORF3, respectively. Subsequently, protocols with pORF1 or pORF3 showed significantly decreased protective efficacy compared to pORF2 alone. Overall, our data suggested that the ORF1- and ORF3-encoded Rep and ORF3 proteins may interfere with the cellular, humoral and protective immunity of the ORF2-encoded Cap protein in vivo.

Fine mapping of antigenic epitopes on capsid proteins of porcine circovirus, and antigenic phenotype of porcine circovirus type 2.

Type 2 porcine circovirus (PCV2) is associated with post-weaning multisystemic wasting syndrome in pigs. In this study, three monoclonal antibodies (mAbs) against the capsid protein (Cap) of PCV2, eight mAbs to Cap of type 1 porcine circovirus (PCV1) and five mAbs specific for Cap of both PCV1 and PCV2, were generated and used to finely map the antigenic sites of PCV1 and PCV2, and to identify the antigenic phenotype of PCV2 with different length of genome. Five linear B-cell epitopes, including the residues 231-233 and 195-202 specific for PCV2, residues 92-103 specific for PCV1, and residues 156-162 and 175-192 shared between PCV1 and PCV2, were finely defined with synthetic peptides, and the critical residue in epitope 231-233 and 156-162 was located at residues 233 ((233)Proline) and 156 ((156)Tyrosine), respectively. The conformational epitopes recognized by mAbs with neutralizing activity against both PCV1 and PCV2 were detected in transfected PK-15 and the residues 231-233 also participated in the formation of conformational epitopes. Analysis of antigenic diversity on these epitopes exhibited three antigenic phenotypes of PCV2, (1766)PCV2, (1767)PCV2 and (1768)PCV2 using mAbs. The results from this study first demonstrated the different antigenic phenotype between PCV2 isolates.

Protective immunity against porcine circovirus 2 by vaccination with ORF2-based DNA and subunit vaccines in mice.

The protective immune response against porcine circovirus 2 (PCV2) infection in mice was characterized using flow cytometric analysis (FCM), assays of antibody (of different IgG isotypes) and viraemia, and histopathological examination. An open reading frame 2 plasmid (pORF2) and the capsid protein (Cap) of PCV2 were used as DNA and subunit vaccines, respectively. In FCM analysis, although pORF2 and Cap alone showed comparable efficacy in eliciting lymphoproliferative responses and Cap-specific CD4(+) T cells, pORF2 was superior to the Cap protein in triggering CD8(+) T cells. A virus neutralization assay showed that pORF2 evoked stronger recall virus-neutralizing (VN) antibody responses than the Cap protein on PCV2 challenge. Correspondingly, VN antibody kinetics coincided with those of Cap-specific IgG2a, but not with the kinetics of IgG and IgG1. Following virus challenge, real-time PCR and histopathological analysis confirmed that only low viral DNA loads and mild microscopic lesions appeared in pORF2-immunized mice. These findings indicate that CD8(+) T cells and VN antibody responses correlating mainly with Cap-specific IgG2a play crucial roles in protecting against PCV2 infection, and that the protective immunity induced by the pORF2 plasmid is superior to that induced by the PCV2 Cap protein.