Sustained Release of Nitric Oxide-Mediated Angiogenesis and Nerve Repair by Mussel-Inspired Adaptable Microreservoirs for Brain Traumatic Injury Therapy.

Traumatic brain injury (TBI) triggers inflammatory response and glial scarring, thus substantially hindering brain tissue repair. This process is exacerbated by the accumulation of activated immunocytes at the injury site, which contributes to scar formation and impedes tissue repair. In this study, a mussel-inspired nitric oxide-release microreservoir (MINOR) that combines the features of reactive oxygen species (ROS) scavengers and sustained NO release to promote angiogenesis and neurogenesis is developed for TBI therapy. The injectable MINOR fabricated using a microfluidic device exhibits excellent monodispersity and gel-like self-healing properties, thus allowing the maintenance of its structural integrity and functionality upon injection. Furthermore, polydopamine in the MINOR enhances cell adhesion, significantly reduces ROS levels, and suppresses inflammation. Moreover, a nitric oxide (NO) donor embedded into the MINOR enables the sustained release of NO, thus facilitating angiogenesis and mitigating inflammatory responses. By harnessing these synergistic effects, the biocompatible MINOR demonstrates remarkable efficacy in enhancing recovery in mice. These findings benefit future therapeutic interventions for patients with TBI.

Ixekizumab is effective in the long-term management in moderate-to-severe plaque psoriasis: results from an Italian retrospective cohort study (the LOTIXE study).

PURPOSE: Ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A approved for the treatment of moderate-to-severe plaque psoriasis. The objective of this study was to describe the real-world long-term effectiveness of ixekizumab in patients with plaque psoriasis in Italy. MATERIALS AND METHODS: A retrospective study was conducted in patients affected by moderate-to-severe plaque psoriasis who were continuously treated with ixekizumab for at least 12 months. Patient data was obtained at 4-weeks, 12-weeks and 6-, 12-, 18- and 24-months after baseline (June 2017 and September 2019) from 10 sites. Results were analyzed by complete case approach, with sensitivity analysis performed to evaluate the impact of missing data. RESULTS: A total of 198 patients were enrolled in the study. At Month 24, 94.3% of patients achieved PASI75 response, while 85.1 and 71.8% achieved PASI90 and PASI100, respectively; and 91.1% of the patients achieved absolute PASI score ≤2. Patients experienced psoriasis improvement at 4 weeks after starting treatment, and improvement was maintained with continued ixekizumab use. The quality of life of patients also improved significantly starting at Week 12, with sustained effect in the long term. CONCLUSION: This 24-month observational cohort study confirmed that ixekizumab is effective in the long-term management of patients with moderate-to-severe plaque psoriasis.

MYL9 deficiency is neonatal lethal in mice due to abnormalities in the lung and the muscularis propria of the bladder and intestine.

Class II myosin complexes are responsible for muscle contraction as well as other non-sarcomeric contractile functions in cells. Myosin heavy chain molecules form the core of these structures, while light chain molecules regulate their stability and function. MYL9 is a light chain isoform that is thought to regulate non-sarcomeric myosin. However, whether this in only in specific cell types or in all cells remains unclear. To address this, we generated MYL9 deficient mice. These mice die soon after birth with abnormalities in multiple organs. All mice exhibited a distended bladder, shortening of the small intestine and alveolar overdistension in the lung. The Myl9 allele in these mice included a LacZ reporter knockin that allowed for mapping of Myl9 gene expression. Using this reporter, we show that MYL9 expression is restricted to the muscularis propria of the small intestine and bladder, as well as in the smooth muscle layer of the bronchi in the lung and major bladder vessels in all organs. This suggests that MYL9 is important for the function of smooth muscle cells in these organs. Smooth muscle dysfunction is therefore likely to be the cause of the abnormalities observed in the intestine, bladder and lung of MYL9 deficient mice and the resulting neonatal lethality.

The applications of B. coagulans TCI711 in alcohol elimination.

This study demonstrates the applications of Bacillus coagulans in alcohol elimination. Bacillus coagulans has recently drawn tremendous interest in the food industry and medicine considering its great environmental tolerance and beneficial effects on improving gastrointestinal diseases. However, few scientific reports connect its utilities with alcohol elimination. In this study, we introduced the unique strain B. coagulans TCI711 for such exploration. TCI711 contained alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) by mass spectrum and resisted gastric acid and bile acid. Also, taking TCI711 capsules for a week can significantly improve alcohol metabolism in humans (breath alcohol level indicated 0 mg/kg in 2 h after drinking 75 mL of whisky). In brief, this exploratory research unveiled the potent applications of B. coagulans in alcohol elimination in humans.

Examining the use of allopurinol: Perspectives from recent drug injury relief applications.

BACKGROUND/PURPOSE: Previous studies have reported that the indication and starting dose of allopurinol may be associated with the incidence of hypersensitive reactions. As allopurinol-related severe cutaneous adverse reactions (SCARs) constitute a significant proportion of drug injury relief applications in Taiwan, this study sought to examine allopurinol use and related adverse reactions through an analysis of recent drug injury relief applications. METHODS: Allopurinol-related drug injury relief applications from 1999 to 2016 were collected, and descriptive statistical methods were used to analyze recent applications dating from 2011 to 2016. RESULTS: A total of 174 allopurinol-related drug injury relief applications were submitted between 2011 and 2016, with the majority involving cases over the age of 65 (75.3%; mean age of all cases was 69.2). Most allopurinol-related drug injuries concerned the skin (173 out of 174 cases, 99.4%). The majority of cases had other co-morbidities such as cardiovascular disease/hypertension (86.2%), chronic kidney disease (58.6%), or diabetes (46.6%). Over 70% of cases initiated allopurinol at a dose of 100 mg/day or less. Analysis revealed that the greatest number of cases (44.6%) occurred in those with an estimated glomerular filtration rate (eGFR) between 15 and 60 mL/min/1.73 m2 and who initiated allopurinol at a dose of 100 mg/day. CONCLUSION: Old age and renal dysfunction are key risk factors for allopurinol hypersensitivity. When considering allopurinol for elderly patients with impaired kidney function, a full risk-benefit assessment, dosage adjustments, and careful monitoring may be warranted.

Probiotic BSH Activity and Anti-Obesity Potential of Lactobacillus plantarum Strain TCI378 Isolated from Korean Kimchi.

Lactobacillus (Lab.) is a human probiotic beneficial for the prevention and improvement of disease, yet properties of different Lab. strains are diverse. To obtain a Lab. strain that possesses greater potential against gastrointestinal dysfunction, we isolated Lactobacillus plantarum TCI378 (TCI378) from naturally fermented Korean kimchi. TCI378 has shown potential as probiotic since it can survive at pH 3.0 and in the presence of 0.3% bile acid. The bile salt hydrolase activity of TCI378 was shown by formation of opaque granular white colonies on solid de Man Rogosa Sharpe (MRS) medium supplemented with taurodeoxycholic acid, and its cholesterol-lowering ability in MRS medium supplemented with cholesterol. The metabolites of TCI378 from liquid culture in MRS medium prevented emulsification of bile salts. Moreover, both the metabolites of TCI378 and the dead bacteria reduced oil droplet accumulation in 3T3-L1, as detected by Oil red O staining. The expressions of adipocyte-specific genes perilipin 1 and glucose transporter type 4 were suppressed by the metabolites of TCI378, indicating TCI378 may have anti-obesity effects in adipocytes. These in vitro data show the potential of the prophylactic applications of TCI378 and its metabolites for reducing fat and lowering cholesterol.

Formation of covalently modified folding intermediates of simian virus 40 Vp1 in large T antigen-expressing cells.

The folding and pentamer assembly of the simian virus 40 (SV40) major capsid protein Vp1, which take place in the infected cytoplasm, have been shown to progress through disulfide-bonded Vp1 folding intermediates. In this report, we further demonstrate the existence of another category of Vp1 folding or assembly intermediates: the nonreducible, covalently modified mdVp1s. These species were present in COS-7 cells that expressed a recombinant SV40 Vp1, Vp1ΔC, through plasmid transfection. The mdVp1s persisted under cell and lysate treatment and SDS-PAGE conditions that are expected to have suppressed the formation of artifactual disulfide cross-links. As shown through a pulse-chase analysis, the mdVp1s were derived from the newly synthesized Vp1ΔC in the same time frame as Vp1's folding and oligomerization. The apparent covalent modifications occurred in the cytoplasm within the core region of Vp1 and depended on the coexpression of the SV40 large T antigen (LT) in the cells. Analogous covalently modified species were found with the expression of recombinant polyomavirus Vp1s and human papillomavirus L1s in COS-7 cells. Furthermore, the mdVp1s formed multiprotein complexes with LT, Hsp70, and Hsp40, and a fraction of the largest mdVp1, md4, was disulfide linked to the unmodified Vp1ΔC. Both mdVp1 formation and most of the multiprotein complex formation were blocked by a Vp1 folding mutation, C87A-C254A. Our observations are consistent with a role for LT in facilitating the folding process of SV40 Vp1 by stimulating certain covalent modifications of Vp1 or by recruiting certain cellular proteins.