Vaccines, Vol. 6, Pages 12: Meningococcal Vaccines: Current Status and Emerging Strategies

Vaccines, Vol. 6, Pages 12: Meningococcal Vaccines: Current Status and Emerging Strategies

Vaccines doi: 10.3390/vaccines6010012

Authors: Pumtiwitt C. McCarthy Abeer Sharyan Laleh Sheikhi Moghaddam

Neisseria meningitidis causes most cases of bacterial meningitis. Meningococcal meningitis is a public health burden to both developed and developing countries throughout the world. There are a number of vaccines (polysaccharide-based, glycoconjugate, protein-based and combined conjugate vaccines) that are approved to target five of the six disease-causing serogroups of the pathogen. Immunization strategies have been effective at helping to decrease the global incidence of meningococcal meningitis. Researchers continue to enhance these efforts through discovery of new antigen targets that may lead to a broadly protective vaccine and development of new methods of homogenous vaccine production. This review describes current meningococcal vaccines and discusses some recent research discoveries that may transform vaccine development against N. meningitidis in the future.

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Antibiotics, Vol. 7, Pages 16: Protective Effects of Bacteriophages against Aeromonas hydrophila Species Causing Motile Aeromonas Septicemia (MAS) in Striped Catfish

Antibiotics, Vol. 7, Pages 16: Protective Effects of Bacteriophages against Aeromonas hydrophila Species Causing Motile Aeromonas Septicemia (MAS) in Striped Catfish

Antibiotics doi: 10.3390/antibiotics7010016

Authors: Tuan Son Le Thi Hien Nguyen Hong Phuong Vo Van Cuong Doan Hong Loc Nguyen Minh Trung Tran Trong Tuan Tran Paul C. Southgate D. İpek Kurtböke

To determine the effectivity of bacteriophages in controlling the mass mortality of striped catfish (Pangasianodon hypophthalmus) due to infections caused by Aeromonas spp. in Vietnamese fish farms, bacteriophages against pathogenic Aeromonas hydrophila were isolated. A. hydrophila-phage 2 and A. hydrophila-phage 5 were successfully isolated from water samples from the Saigon River of Ho Chi Minh City, Vietnam. These phages, belonging to the Myoviridae family, were found to have broad activity spectra, even against the tested multiple-antibiotic-resistant Aeromonas isolates. The latent periods and burst size of phage 2 were 10 min and 213 PFU per infected host cell, respectively. The bacteriophages proved to be effective in inhibiting the growth of the Aeromonas spp. under laboratory conditions. Phage treatments applied to the pathogenic strains during infestation of catfish resulted in a significant improvement in the survival rates of the tested fishes, with up to 100% survival with MOI 100, compared to 18.3% survival observed in control experiments. These findings illustrate the potential for using phages as an effective bio-treatment method to control Motile Aeromonas Septicemia (MAS) in fish farms. This study provides further evidence towards the use of bacteriophages to effectively control disease in aquaculture operations.

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LncRNA RP11-552M11.4 promotes cells proliferation, migration and invasion by targeting BRCA2 in ovarian cancer

Summary

This study aimed to investigate the effect of long non-coding RNA (lncRNA) RP11-552M11.4 on cells proliferation, apoptosis, migration and invasion as well as its targeting genes in epithelial ovarian cancer (EOC) cells. LncRNA RP11-552M11.4 expression was detected in 67 tumor tissues and paired adjacent tissues obtained from EOC patients. lncRNA RP11-552M11.4 mimic/inhibitor plasmids were transferred into ovarian cancer cells (SKOV3, A-2780) and normal ovarian epithelial cells (IOSE80 cells). In addition, rescue experiment was performed by transferring BRCA2 inhibitor&lncRNA RP11-552M11.4 inhibitor plasmids into SKOV3 and A-2780 cells. qPCR, western blot, CKK-8, AV/PI, wound-healing and matrigel invasion assays were performed to detect RNA expression, protein expression, cells proliferation, apoptosis, migration and invasion respectively. LncRNA RP11-552M11.4 expression was elevated in tumor tissues compared with paired adjacent tissues and correlated with higher pathological grade, FIGO stage and worse overall survival in EOC patients. LncRNA RP11-552M11.4 promoted SKOV3 cells proliferation, migration and invasion while inhibited the apoptosis. Rescue experiment and luciferase reporter assay revealed that lncRNA RP11-552M11.4 regulated SKOV3 cells functions via binding BRCA2. Further experiments in A-2780 cells also validated that lncRNA RP11-552M11.4 induced A-2780 cells proliferation while repressed apoptosis by targeting BRCA2. In addition, upregulation of lncRNA RP11-552M11.4 increased IOSE80 cells proliferation, migration and invasion while decreased apoptosis. In conclusion, lncRNA RP11-552M11.4 correlates with worse prognosis, and promotes cells proliferation, migration, invasion and inhibits cells apoptosis by downregulating BRCA2 in EOC.

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Bortezomib plus dexamethasone versus thalidomide plus dexamethasone for relapsed or refractory multiple myeloma

Abstract

A randomized phase II selection design study (JCOG0904) was conducted to evaluate the more promising regimen between bortezomib (Bor) plus dexamethasone (Dex: BD) and thalidomide (Thal) plus Dex (TD) in Bor and Thal-naïve patients with relapsed or refractory multiple myeloma (RRMM). Patients ≥ 20 and < 80 years old with a documented diagnosis of symptomatic multiple myeloma (MM) with ≥ 1 prior therapies were randomized to receive BD (Bor 1.3 mg/m²) or TD (Thal 200 mg/day). In both arms, 8 cycles of induction (3-week cycle) were followed by maintenance phase (5-week cycle) until disease progression, unacceptable toxicity or patient refusal. The primary endpoint was 1-year progression-free survival (PFS). Forty-four patients were randomized and assigned to receive BD and TD (n = 22, each). At a median follow-up of 34.3 months, the 1-year PFS in the BD and TD arms were 45.5% (95% confidence interval (CI) 24.4%-64.3%) and 31.8% (95%CI 14.2%-51.1%), respectively, while the overall response rates were 77.3% and 40.9% respectively. The 3-year overall survival (OS) was 70.0% (95%CI 44.9%-85.4%) in the BD, and 48.8% (95%CI 25.1%-69.0%) in the TD arm. Among grade 3/4 adverse events, thrombocytopenia (54.5% vs 0%) and sensory peripheral neuropathy (22.7% vs 9.1%) were more frequent in BD when compared with the TD arm. BD had better outcomes than TD with regard to the 1-year PFS and 3-year OS. Thus, BD was prioritized over TD for further investigations in Bor and Thal-naïve RRMM patients. (UMIN000003135).

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The roles of protein kinase R in cancer: Potential as a therapeutic target

Summary

Double-stranded (ds) RNA-dependent protein kinase (PKR) is a ubiquitously expressed serine/threonine protein kinase. It was initially identified as an innate immune anti-viral protein induced by interferon (IFN) and activated by dsRNA. PKR is recognized as a key executor of the antiviral host defense. Moreover, it contributes to inflammation and immune regulation through several signaling pathways. In addition to IFN and dsRNA, PKR is activated by multiple stimuli and regulates various signaling pathways including the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells pathways. PKR was initially thought to be a tumor suppressor due to its ability to suppress cell growth and interact with major tumor suppressor genes. However, in several types of malignant diseases such as colon and breast cancers, its role remains controversial. In hepatocellular carcinoma, hepatitis C virus is the main cause of liver cancer, and PKR inhibits HCV replication, indicating its role as a tumor suppressor. However, PKR is overexpressed in cirrhotic patients, and acts as a tumor promoter through enhancement of cancer cell growth by mediating MAPK or signal transducer and activator of transcription pathways. Moreover, PKR is reportedly required for the activation of inflammasomes and influences metabolic disorders. In this review, we introduce the multifaceted roles of PKR such as antiviral function, tumor cell growth, regulation of inflammatory immune responses, and maintaining metabolic homeostasis; and discuss future perspectives on PKR biology including its potential as a therapeutic target for liver cancer.

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Frequency of unsatisfactory cervical cytology smears in cancer screening of Japanese women: A systematic review and meta-analysis

Abstract

The Bethesda system (TBS) has been used for cervical cytological diagnosis in Japan since 2008. Evaluation of specimen adequacy is the most important aspect of quality assurance and for precise diagnosis in TBS. A systematic review and meta-analysis were performed to assess the unsatisfactory specimen rate in the primary cervical cancer screening setting in Japan.

Ovid MEDLINE and Ichushi-Web were searched from inception through May 2017. Prospective and retrospective studies that reported the proportion of unsatisfactory specimens in healthy asymptomatic Japanese women in a cervical cancer screening program were eligible for inclusion; 17 studies were included in the meta-analysis.

The random-effects model meta-analysis calculated summary estimates of the unsatisfactory rate of 0.60% (95% CI: 0.18 – 1.96%; I² = 99%) for conventional cytology and 0.04% (95% CI: 0.00 – 0.35%; I² = 99%) for liquid-based cytology (LBC). However, comparative results between conventional and liquid-based cytology, based on 4 direct and 9 comparative studies, showed no significant difference (summary odds ratio = 3.5×10^-2 favoring LBC [95% CI: 6.9×10^-4 – 1.7]; I² = 98%). In the subgroup analyses and meta-regressions, use of non-cotton devices for conventional cytology and use of a particular platform for LBC were associated with lower unsatisfactory rates. Meta-regression also suggested chronological improvement in unsatisfactory rates for both tests.

In Japanese cervical cancer screening programs, conventional cytology remains prevalent. Future research needs to focus on evaluating the impact of screening programs using LBC by comparing the accuracy, performance, and cost-effectiveness with conventional cytology in the Japanese population.

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IJMS, Vol. 19, Pages 649: Hazard Screening Methods for Nanomaterials: A Comparative Study

IJMS, Vol. 19, Pages 649: Hazard Screening Methods for Nanomaterials: A Comparative Study

International Journal of Molecular Sciences doi: 10.3390/ijms19030649

Authors: Barry Sheehan Finbarr Murphy Martin Mullins Irini Furxhi Anna Costa Felice Simeone Paride Mantecca

Hazard identification is the key step in risk assessment and management of manufactured nanomaterials (NM). However, the rapid commercialisation of nano-enabled products continues to out-pace the development of a prudent risk management mechanism that is widely accepted by the scientific community and enforced by regulators. However, a growing body of academic literature is developing promising quantitative methods. Two approaches have gained significant currency. Bayesian networks (BN) are a probabilistic, machine learning approach while the weight of evidence (WoE) statistical framework is based on expert elicitation. This comparative study investigates the efficacy of quantitative WoE and Bayesian methodologies in ranking the potential hazard of metal and metal-oxide NMs—TiO2, Ag, and ZnO. This research finds that hazard ranking is consistent for both risk assessment approaches. The BN and WoE models both utilize physico-chemical, toxicological, and study type data to infer the hazard potential. The BN exhibits more stability when the models are perturbed with new data. The BN has the significant advantage of self-learning with new data; however, this assumes all input data is equally valid. This research finds that a combination of WoE that would rank input data along with the BN is the optimal hazard assessment framework.

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