Changes in Diarrhea Score, Nutrient Digestibility, Zinc Utilization, Intestinal Immune Profiles, and Fecal Microbiome in Weaned Piglets by Different Forms of Zinc.

Twenty weaned piglets with initial body weight of 6.83 ± 0.33 kg (21 day of age, LYD) were randomly assigned to four treatments for a two-week feeding trial to determine the effects of different dietary zinc on nutrient digestibility, intestinal health, and microbiome of weaned piglets. The dietary treatments included a negative control (CON), standard ZnO (ZnO, 2500 ppm), zinc chelate with glycine (Chelate-ZnO, 200 ppm), and nanoparticle-sized ZnO (Nano-ZnO, 200 ppm). At 0 to 1 week, the diarrhea score was decreased in the CON group compared with the ZnO, Chelate-ZnO, and Nano-ZnO group. In overall period, the ZnO and Nano-ZnO groups exhibited improved diarrhea scores compared to the CON group. The apparent total tract digestibility of dry matter and gross energy was the lowest in the CON group after one week. Compared to the ZnO group, the chelate-ZnO group exhibited higher proportion of T-bet+ and FoxP3+ T cells and the nano-ZnO group had higher numbers of RORgt+ and GATA3+ T cells in the mesenteric lymph nodes. ZnO group increased IL-6 and IL-8 levels in the colon tissues and these positive effects were observed in both chelate ZnO and nano-ZnO groups with lower level. The 16S rRNA gene analysis showed that the relative abundance of Prevotella was higher in the ZnO-treated groups than in the CON group and that of Succinivibrio was the highest in the nano-ZnO group. The relative abundance of Lactobacillus increased in the ZnO group. In conclusion, low nano-ZnO levels have similar effects on nutrient digestibility, fecal microflora, and intestinal immune profiles in weaning pigs; thus, nano-ZnO could be used as a ZnO alternative for promoting ZnO utilization and intestinal immunity.

PEGylated nanoparticle albumin-bound steroidal ginsenoside derivatives ameliorate SARS-CoV-2-mediated hyper-inflammatory responses.

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on a global scale urges prompt and effective countermeasures. Recently, a study has reported that coronavirus disease-19 (COVID-19), the disease caused by SARS-CoV-2 infection, is associated with a decrease in albumin level, an increase in NETosis, blood coagulation, and cytokine level. Here, we present drug-loaded albumin nanoparticles as a therapeutic agent to resolve the clinical outcomes observed in severe SARS-CoV-2 patients. PEGylated nanoparticle albumin-bound (PNAB) was used to promote prolonged bioactivity of steroidal ginsenoside saponins, PNAB-Rg6 and PNAB-Rgx365. Our data indicate that the application of PNAB-steroidal ginsenoside can effectively reduce histone H4 and NETosis-related factors in the plasma, and alleviate SREBP2-mediated systemic inflammation in the PBMCs of SARS-CoV-2 ICU patients. The engineered blood vessel model confirmed that these drugs are effective in suppressing blood clot formation and vascular inflammation. Moreover, the animal model experiment showed that these drugs are effective in promoting the survival rate by alleviating tissue damage and cytokine storm. Altogether, our findings suggest that these PNAB-steroidal ginsenoside drugs have potential applications in the treatment of symptoms associated with severe SARS-CoV-2 patients, such as coagulation and cytokine storm.

Lung-selective 25-hydroxycholesterol nanotherapeutics as a suppressor of COVID-19-associated cytokine storm.

In response to the coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), global efforts are focused on the development of new therapeutic interventions. For the treatment of COVID-19, selective lung-localizing strategies hold tremendous potential, as SARS-CoV-2 invades the lung via ACE2 receptors and causes severe pneumonia. Similarly, recent reports have shown the association of COVID-19 with decreased 25-hydroxycholesterol (25-HC) and increased cytokine levels. This mechanism, which involves the activation of inflammatory NF-κB- and SREBP2-mediated inflammasome signaling pathways, is believed to play a crucial role in COVID-19 pathogenesis, inducing acute respiratory distress syndrome (ARDS) and sepsis. To resolve those clinical conditions observed in severe SARS-CoV-2 patients, we report 25-HC and didodecyldimethylammonium bromide (DDAB) nanovesicles (25-HC@DDAB) as a COVID-19 drug candidate for the restoration of intracellular cholesterol level and suppression of cytokine storm. Our data demonstrate that 25-HC@DDAB can selectively accumulate the lung tissues and effectively downregulate NF-κB and SREBP2 signaling pathways in COVID-19 patient-derived PBMCs, reducing inflammatory cytokine levels. Altogether, our findings suggest that 25-HC@DDAB is a promising candidate for the treatment of symptoms associated with severe COVID-19 patients, such as decreased cholesterol level and cytokine storm.

Arginine addition in a diet for weaning pigs can improve the growth performance under heat stress.

The effects of arginine (Arg) and methionine (Met) supplementation on nutrient use in pigs were determined under hot season conditions. A total of five experimental diets including basal diet (CON) were supplemented with two types of amino acids (Arg and Met) and two different amounts of amino acids (0.2% and 0.4%). Under hot season condition, pigs fed with additional Arg were significantly higher in average daily gain (ADG) than the CON group and the ADG increased linearly (p < 0.05) with increasing Arg supplementation. But there was no significant difference with Met supplementation (p > 0.05). The apparent ileal digestibility (AID) of amino acids had no significant difference among treatments (p > 0.05), while d-reactive oxygen metabolites (d-ROMs) concentration in treatments with Arg supplementation, were significantly higher (p < 0.05) than other treatments. In conclusion, exposure of pigs to heat stress does not affect the AID of amino acid, whereas pig fed with additional Arg improved ADG and feed efficiency under heat stress condition.

Preparation and Evaluation of Eudragit L100-PEG Proliponiosomes for Enhanced Oral Delivery of Celecoxib.

PEGylated Eudragit L100 (ELP)-containing proliponiosomes (PLNs) were developed for improved oral delivery of celecoxib (CXB). The successful introduction of PEG 2000 or 5000 to Eudragit L100 (EL) was confirmed via proton nuclear magnetic resonance analysis of which calculated molar substitution ratio of PEG to EL was 36.0 or 36.7, respectively. CXB, ELP, phospholipid, and non-ionic surfactants were dissolved in dimethyl sulfoxide and lyophilized to produce CXB-loaded PLNs (CXB@PLNs). The physical state of CXB@PLNs was evaluated using differential scanning calorimetry and powder X-ray diffractometry, which revealed that crystalline CXB was transformed into amorphous form after the fabrication procedure. The reconstitution of CXB@PLNs in aqueous media generated CXB-loaded liponiosomes with nano-sized mean diameters and spherical morphology. CXB@PLNs displayed enhanced dissolution rate and permeability compared to CXB suspension. In vivo pharmacokinetic studies performed on rats demonstrated the improved oral bioavailability of CXB@PLNs compared to that of CXB suspension. No serious systemic toxicity was observed in the blood biochemistry tests performed on rats. These results suggest that the developed PLNs could be promising oral delivery systems for improving the bioavailability of poorly water-soluble drugs, such as CXB.

Long-term Outcome of Incision and Curettage Treatment in Patients with Lacrimal Gland Ductulitis.

PURPOSE: To describe the effects and long-term outcomes of incision and curettage treatment in patients with lacrimal gland ductulitis. METHODS: Twenty-four patients (24 eyes) with lacrimal gland ductulitis who were treated at Saevit Eye Hospital from June 2010 to November 2016. All patients underwent incision and curettage through the lacrimal ductule, and granules or concretions were removed. After the procedure, oral and topical antibiotics, oral anti-inflammatory agent were used for a week. Clinical presentations of the patients were analyzed. The resolution of symptoms and inflammatory signs and recurrence were evaluated more than 12 months after the procedure including telephone follow-up by a specialist nurse. RESULTS: Common symptoms were a painful, swelling mass with mucous discharge (17 eyes) and conjunctival injection (7 eyes) at the lateral canthal area. During the procedure, 22 patients (91.7%) had typical sulfur granule of Actinomyces, and 10 patients (41.7%) had many cilia in the expressed debris from the ductule. Twenty-three of 24 patients had resolution of symptoms after the procedure and all but one patient (95.8%) showed no recurrence. CONCLUSIONS: Incision and curettage is a simple and less invasive procedure that may be considered as a first treatment option for lacrimal gland ductulitis. Furthermore, incision and curettage of the affected lacrimal ductule has been shown to be effective at minimizing long-term recurrence of lacrimal ductulitis.