Antioxidant and anti-inflammatory protective effects of yellowtail (Seriola quinqueradiata) milt hydrolysates on human intestinal epithelial cells in vitro and dextran sodium sulphate-induced mouse colitis in vivo.

Milt is an underutilized fish processing by-product containing valuable nutrients for human health. Here, a gastrointestinal hydrolysate of degreased yellowtail (Seriola quinqueradiata) milt contained 70.6% arginine-rich protein, 20% nucleic acids, 7.1% minerals and 2.3% carbohydrates. Yellowtail milt hydrolysates (YMH) effectively attenuated the H2O2-induced burst of intracellular reactive oxygen species, plasma membrane impairment, loss of cell viability, interleukin 8 production and the expression of claudin-4 and occludin in Caco-2 cells with its protein fraction playing a greater antioxidant role than its nucleic acid fraction. YMH also significantly counteracted the tumor necrosis factor α- and interleukin 1ß-stimulated interleukin 8 production and cyclooxygenase-2 and inducible nitric oxide synthase expression in Caco-2 cells and inhibited the production of nitric oxide and proinflammatory mediators in lipopolysaccharide-stimulated RAW 264.7 cells depending on its protein fraction, rather than its nucleic acid fraction. YMH and a positive drug 5-aminosalicylic acid were intragastrically administered to C57BL/6 mice daily for 7 days during and after 4-day dextran sodium sulphate exposure. Based on clinical signs, colon histopathology and biochemical analysis of colonic tight junction proteins, mucus compositions and goblet cells, YMH ameliorated mouse colitis symptoms and intestinal epithelial barrier dysfunction more effectively than 5-aminosalicylic acid. According to myeloperoxidase activity, proinflammatory cytokines and NF-κB, YMH and 5-aminosalicylic acid exerted equivalent inhibitory effects on colonic and systemic inflammation. Overall, YMH have considerable antioxidant and anti-inflammatory efficacies to maintain gut health.

Research Progress on Exosomes in Osteonecrosis of the Femoral Head.

Osteonecrosis of the femoral head (ONFH) is a progressive disease that often necessitates hip replacement if hip preservation therapy fails. ONFH places a heavy economic burden and severe psychological pressure on patients. At present, ONFH is treated by either surgical or non-surgical methods. In clinical practice, stem cells combined with surgery has achieved some positive results, but many problems remain to be resolved. Exosomes are small vesicles of 30-150 nm, which are rich in various nucleic acids, proteins, and small molecules depending on the cells from which they are derived. A growing number of studies have found that exosomes play an important role in tissue damage repair. In comparison with stem cells, exosomes have lower immunogenicity. Also, exosomes can promote cell proliferation and inhibit tumor growth. In addition, exosomes can also be used as natural carriers of drugs. Many studies have shown that exosomes have therapeutic effects in hormone-induced ONFH. Exosomes have the effect of promoting vascular regeneration and show good application prospects in ONFH. Here, we present a review of studies on the application of exosomes in ONFH to provide a reference for future research.

Beyond Pegylated Interferon-Alpha: New Treatments for Hepatitis Delta.

Persistent coinfection with the hepatitis B/D viruses (HDV) represents the most severe form of viral hepatitis. Hepatitis D often leads to liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma. The current treatment options are limited as only pegylated interferon-alpha (PEG-IFNa) has efficacy against HDV. However, treatment response is still unsatisfactory with 25-40% HDV RNA suppression after 1-2 years. In addition, late HDV RNA relapses have been described during long-term follow-up. Fortunately, new treatment options for patients with chronic hepatitis delta are now on the horizon. The hepatocyte entry inhibitor bulevirtide (formerly myrcludex B) and the farnesyl transferase inhibitor lonafarnib are currently explored in patients with chronic hepatitis delta in Phase 3 clinical studies. The nucleic acid inhibitor REP-2139-Ca and PEG-IFN-lambda are studied in Phase 2 trials. We here summarize data on the efficacy of these new antiviral drugs and the existing safety data on the treatment of HDV infection.

Therapeutic Effects of Ribunucleinate (Ribonucleotides) in Immuno-Inflammatory and Arthritic Diseases.

Ribonucleic acids from different organs and from yeast have been used for the treatment of chronic and degenerative diseases in the context of naturopathic medicine in the last 60 years. This chapter provides general information about ribonucleinates as therapeutic agents. Past and present pharmacological and clinical investigations are discussed in the field of the central nervous system, sensory organs, cancer and degenerative diseases of joints and vertebra.

Efficacy and safety of MCNA in patients with nonmuscle invasive bladder cancer at high risk for recurrence and progression after failed treatment with bacillus Calmette-Guérin.

PURPOSE: Patients with high risk recurrences after bacillus Calmette-Guérin failure have limited options. We performed an open label study to evaluate the efficacy and safety of intravesical MCNA in this setting. MATERIALS AND METHODS: Patients were treated intravesically with 8 mg MCNA weekly for 6 weeks followed by 3 weekly instillations at months 3, 6, 12, 18 and 24. Cystoscopy and cytology were performed every 3 months for 2 years with mandatory biopsy at 6 months and as clinically indicated thereafter. The primary efficacy end point was the disease-free survival rate at 1 year. RESULTS: A total of 129 patients were enrolled in study, including 91 with carcinoma in situ with or without papillary disease and 38 with papillary only tumors. Most patients had high risk disease. A total of 107 cases were bacillus Calmette-Guérin refractory and 2 or more prior bacillus Calmette-Guérin induction courses had been given in 68. Median followup in all patients was 34.7 months. The overall disease-free survival rate was 25.0% at 1 year and 19.0% at 2 years. In patients with papillary only tumors the disease-free survival rate was 35.1% and 32.2% at 1 and 2 years, respectively. The median disease-free duration in the 30 responders was 32.7 months. The progression-free survival rate was 87.3%, 79.8% and 77.7% at 1, 2 and 3 years, respectively, with a progression event in 28 patients. MCNA was well tolerated and few adverse events led to treatment discontinuation. CONCLUSIONS: Intravesical MCNA achieved significant activity in patients at high risk with nonmuscle invasive bladder cancer in whom bacillus Calmette-Guérin treatment failed, especially those with papillary only tumors and those with bacillus Calmette-Guérin relapse. A durable response was seen, particularly in patients with a response at 1 year. MCNA offers an option for patients who are not candidates for or who refuse cystectomy.

Safety considerations for nucleic acid vaccines.

Whilst it is premature to formulate guidelines for the manufacturing requirements of a nucleic acid vaccine, it can never be too early to discuss and debate the issues surrounding the use of a novel biotherapeutic. The major safety issues posed by nucleic acid vaccination include the possibility of transformation (or tumorigenic) events in recipients of a DNA vaccine, the potential formation of anti-DNA antibodies, and unexpected and untoward effects of long-term expression of a foreign antigen. This paper examines the extent to which these points impinge on the safety of DNA vaccines.