The Current Landscape of mRNA Vaccines Against Viruses and Cancer-A Mini Review.

Both infectious viral diseases and cancer have historically been some of the most common causes of death worldwide. The COVID-19 pandemic is a decidedly relevant example of the former. Despite progress having been made over past decades, new and improved techniques are still needed to address the limitations faced by current treatment standards, with mRNA-based therapy emerging as a promising solution. Highly flexible, scalable and cost-effective, mRNA therapy is proving to be a compelling vaccine platform against viruses. Likewise, mRNA vaccines show similar promise against cancer as a platform capable of encoding multiple antigens for a diverse array of cancers, including those that are patient specific as a novel form of personalized medicine. In this review, the molecular mechanisms, biotechnological aspects, and clinical developments of mRNA vaccines against viral infections and cancer are discussed to provide an informative update on the current state of mRNA therapy research.

A novel C-type lectin LvCTL 4.2 has antibacterial activity but facilitates WSSV infection in shrimp (L. vannamei).

Glycan-binding protein C-type lectin (CTL), one of the pattern recognition receptors (PRRs), binds to carbohydrates on the surface of pathogens and elicits antimicrobial responses in shrimp innate immunity. The objective was to identify and characterize a novel C-type lectin LvCTL 4.2 in Litopenaeus vannamei. The LvCTL 4.2 protein consisted of a signal peptide at the N terminal and a carbohydrate-recognition domain (CRD) with a mutated mannose-binding (Glu-Pro-Ala; EPA) motif at the C terminal, and thereby has a putative secreted mannose-binding C-type lectin architecture. LvCTL 4.2 was highly expressed in nervous tissue and stomach. Infection with white spot syndrome virus (WSSV) induced expression of LvCTL 4.2 in shrimp stomach at 12 h post infection. Conversely, there was no obvious upregulation in expression of LvCTL 4.2 in stomach or hepatopancreas of shrimp with AHPND (acute hepatopancreas necrosis disease). Pathogen binding assays confirmed recombinant LvCTL 4.2 protein (rLvCTL 4.2) had significant binding ability with the WSSV virion, Gram-negative, and Gram-positive bacteria. Moreover, rLvCTL 4.2 had strong growth inhibition of Vibrio parahaemolyticus. Silencing LvCTL 4.2 suppressed WSSV replication, whereas pretreatment of WSSV with rLvCTL 4.2 facilitated viral replication in vivo. In conclusion, LvCTL 4.2 acted as a PRR that inhibited AHPND-causing bacteria, but facilitated WSSV pathogenesis.

Effect of Hole Shift on Threshold Characteristics of GaSb-Based Double-Hole Photonic-Crystal Surface-Emitting Lasers.

Photonic-crystal (PC) surface-emitting lasers (SELs) with double-hole structure in the square-lattice unit cell were fabricated on GaSb-based type-I InGaAsSb/AlGaAsSb heterostructures. The relative shift of two holes was varied within one half of the lattice period. We measured the lasing wavelengths and threshold pumping densities of 16 PC-SELs and investigated their dependence on the double-hole shift. The experimental results were compared to the simulated wavelengths and threshold gains of four band-edge modes. The measured lasing wavelength did not exhibit switching of band-edge mode; however, the calculated lowest threshold mode switched as the double-hole shift exceeded one quarter of the lattice period. The identification of band-edge lasing mode revealed that modal gain discrimination was dominated over by its mode wavelength separation.

The gene structure and hypervariability of the complete Penaeus monodon Dscam gene.

Using two advanced sequencing approaches, Illumina and PacBio, we derive the entire Dscam gene from an M2 assembly of the complete Penaeus monodon genome. The P. monodon Dscam (PmDscam) gene is ~266 kbp, with a total of 44 exons, 5 of which are subject to alternative splicing. PmDscam has a conserved architectural structure consisting of an extracellular region with hypervariable Ig domains, a transmembrane domain, and a cytoplasmic tail. We show that, contrary to a previous report, there are in fact 26, 81 and 26 alternative exons in N-terminal Ig2, N-terminal Ig3 and the entirety of Ig7, respectively. We also identified two alternatively spliced exons in the cytoplasmic tail, with transmembrane domains in exon variants 32.1 and 32.2, and stop codons in exon variants 44.1 and 44.2. This means that alternative splicing is involved in the selection of the stop codon. There are also 7 non-constitutive cytoplasmic tail exons that can either be included or skipped. Alternative splicing and the non-constitutive exons together produce more than 21 million isoform combinations from one PmDscam locus in the P. monodon gene. A public-facing database that allows BLAST searches of all 175 exons in the PmDscam gene has been established at http://pmdscam.dbbs.ncku.edu.tw/ .

Cilostazol Attenuates Retinal Oxidative Stress and Inflammation in a Streptozotocin-Induced Diabetic Animal Model.

PURPOSE: To investigate the anti-oxidative and anti-inflammatory effects of cilostazol in the ocular tissues of streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: Diabetes was induced in 6-week-old Wistar rats via peritoneal injections of STZ. The treatment group received cilostazol 18 mg/kg/day for 8 weeks (n = 10), and the diabetic group received phosphate buffer solution (n = 20). The expression of oxidative stress and inflammatory mediators in the ocular tissues was then assessed by reverse-transcription polymerase chain reactions, immunohistochemical (IHC) staining, Western blot analysis, and enzyme-linked immunosorbent assay (ELISA). RESULTS: Reverse-transcription polymerase chain reactions, IHC staining, Western blot analysis, and ELISA showed that cilostazol inhibited mRNA and protein expressions of intercellular adhesion molecule-1, monocyte chemoattractant protein-1 and fractalkine in the retina and aqueous humor (AqH). Consistent with these findings, cilostazol attenuated the activation of nuclear factor-κB (NF-κB) in the diabetic rats. The levels of oxidatively modified DNA (8-OHdG), nitrotyrosine and oxidative lipids (acrolein) were also diminished in the cilostazol-treated group. Chemiluminescence analysis showed that reactive oxygen species (ROS) levels in the AqH was significantly higher in the diabetic rats than in the non-diabetic rats. Treatment with cilostazol significantly reduced the ROS levels in the AqH compared to the diabetic rats. CONCLUSIONS: Our results indicated that cilostazol reduced inflammatory reactions and oxidative stress in diabetic eyes. The anti-inflammatory effects of cilostazol may be indirectly via reducing oxidative stress, inhibiting NF-κB activity, and subsequently decreasing inflammatory mediators. Cilostazol may be beneficial to prevent the progression of diabetic retinopathy.

Intravitreal bevacizumab and panretinal photocoagulation for proliferative diabetic retinopathy associated with vitreous hemorrhage.

PURPOSE: To evaluate the efficacy of intravitreal bevacizumab with panretinal photocoagulation (PRP) in the treatment of proliferate diabetic retinopathy (PDR) with vitreous hemorrhage (VH). METHODS: Forty cases (40 patients) with PDR and persistent VH were prospectively enrolled, with a follow-up period of 12 months or more. Intravitreal bevacizumab injection (1.25 mg) was given, followed by PRP when visualization of peripheral fundus could be obtained. A second injection was administered 4 weeks to 6 weeks after the first injection if no signs of VH decrease were noted. Vitrectomy was performed if VH persisted >12 weeks. The vitreous clear-up time (VCUT) and the rate of vitrectomy were compared with those in a historical control group (40 eyes in 40 patients) who were treated with conventional methods. RESULTS: Thirty-one eyes had 1 injection and 9 eyes (22.5%) received 2 injections. Vitreous clear-up time in the study and control groups were 11.9 +/- 9.5 weeks and 18.1 +/- 12.7 weeks (P = 0.02), respectively. Rates of required vitrectomy were 10% in the study group and 45% in the control group (P = 0.01). CONCLUSION: One or 2 intravitreal injections of 1.25 mg bevacizumab with PRP are associated with rapid regression of VH and may reduce the need for vitrectomy.

Balloon dacryocystoplasty and monocanalicular intubation with Monoka tubes in the treatment of congenital nasolacrimal duct obstruction.

PURPOSE: To report our experience with combined use of balloon dacryocystoplasty and monocanalicular intubation with Monoka tubes for treating congenital nasolacrimal duct obstruction. DESIGN: Retrospective consecutive interventional case series. MATERIALS AND METHODS: This retrospective study consisted of 25 consecutive pediatric patients with congenital nasolacrimal duct obstruction who underwent balloon dacryocystoplasty and monocanalicular intubation with Monoka tubes between November 2003 and November 2006. Outcome evaluations included an ophthalmologic examination and a dye appearance test postoperatively. Age, history of a prior probing and complications related to the main outcome were also analyzed. RESULTS: Thirty-three eyes of 25 patients aged 8 months to 9 years (3.5 +/- 2.4 years old) were included. Of the obstructed ducts treated, 97% (32/33) showed complete resolution of epiphoria. When analyzed by age groups, patients more than 1 year of age had higher success rate (30 successes in 30 patients) than patients less than 1 year of age (two successes in three patients). Statistical analysis revealed no statistically significant difference in success rate between both age groups (p = 0.09). The mean duration of intubation was 5.7 +/- 2.2 months. No significant complication was noted, except that early tube dislodgements occurred in six out of 31 Monoka intubations (19%). CONCLUSIONS: The combined use of balloon dacryocystoplasty and monocanalicular intubation with Monoka tubes is an effective procedure for children with congenital nasolacrimal duct obstruction after failure of conservative treatment or probing.

Recurrent advancing wavelike epitheliopathy from the opposite side of the initial presentation.

PURPOSE: To report an unusual case of advancing wavelike epitheliopathy that recurred at a site opposite to the initially affected site. METHODS: Single interventional case report. This report describes a 50-year-old woman who presented with advancing, wavelike epitheliopathy of her right eye that lasted 2 months. RESULTS: Slit-lamp biomicroscopy revealed wavy, coarse, irregular epithelium extending from the upper limbus to the central cornea. Confocal microscopy revealed abnormal basal epithelial cells with a loss of cellular borders and hyperreflective nuclei. Application of 1% silver nitrate solution onto the superior limbus effectively treated this condition. However, wavy, irregular epithelium was observed 2 years later in the lower limbus. CONCLUSIONS: Advancing wavelike epitheliopathy can occur from the lower limbus and recur from the opposite side of the initial presentation, even after successful treatment with 1% silver nitrate solution.