Diagnostic utility of whole-body computed tomography/pan-scan in trauma: a systematic review and meta-analysis study.

Trauma is a significant cause of mortality and morbidity. It is crucial to diagnose trauma patients quickly to provide effective treatment interventions in such conditions. Whole-body computed tomography (WBCT)/pan-scan is an imaging technique that enables a faster and more efficient diagnosis for polytrauma patients. The purpose of this systematic review and meta-analysis is to evaluate the efficacy of WBCT in diagnosing injuries in polytrauma patients. We will also assess its impact on the mortality rate and length of hospital stay among trauma centers between patients who underwent WBCT and those who did not (non-WBCT). Twenty-seven studies meeting our inclusion criteria were selected among PubMed, Scopus, Web of Science, and Google Scholar. The criteria were centered on the significance of WBCT/pan-scan application in trauma patients. Stata version 15 was used to perform statistical analysis on the data. The authors have also used I2 statistics to evaluate heterogeneity. Egger and Begg's tests were performed to rule out any publication bias. Total of twenty-seven studies including 68,838 trauma patients with a mean age of 45.0 ± 24.7 years were selected. Motor vehicle collisions were the most common cause of blunt injuries (80.0%). Head, neck, and face injuries were diagnosed in 44% (95% CI, 0.28-0.60; I2 = 99.8%), 6% (95% CI, 0.02-0.09; I2 = 97.2%), and 9% (95% CI, 0.05-0.13; I2 = 97.1%), respectively. Chest injuries were diagnosed by WBCT in 39% (95% CI, 0.28-0.51; I2 = 99.8%), abdominal injuries in 23% (95% CI, 0.03-0.43; I2 = 99.9%) of cases, spinal injuries 19% (95% CI, 0.11-0.27; I2 = 99.4%), extremity injuries 33% (95% CI, 0.23-0.43; I2 = 99.2%), and pelvic injuries 11% (95% CI, 0.04-0.18; I2 = 97.4%). A mortality odd ratio of 0.94 (95% CI, 0.83-1.06; I2 = 40.1%) was calculated while comparing WBCT and non-WBCT groups. This systematic review and meta-analysis provide insight into the possible safety, efficacy, and efficiency of WBCT/pan-scan as a diagnostic tool for trauma patients with serious injuries, regardless of their hemodynamic status. In patients with serious injuries from trauma, whether or not there are indicators of hemodynamic instability, our recommended approach is to, wherever possible, perform a WBCT without stopping the hemostatic resuscitation. By using this technology, the optimal surgical strategy for these patients can be decided upon without causing any delays in their final care or greatly raising their radiation dose.

Multi-Epitope Vaccine Candidates Associated with Mannosylated Chitosan and LPS Conjugated Chitosan Nanoparticles Against Brucella Infection.

One promising approach to increase protection against infectious diseases is to use adjuvants that can selectively stimulate the immune responses. In this study, multi-epitope antigens associated with LPS loaded chitosan (LLC) as toll-like receptor agonist or mannosylated chitosan nanoparticle (MCN) as vaccine delivery system were evaluated for their ability to stimulate immune responses to Brucella infection in mice model. Our results indicated that the addition of MCN to our vaccine formulations significantly elicited IFN-γ and IL-2 cytokines and antibody titers, in comparison with the non-adjuvanted vaccine candidates. The present results indicated that multi-epitopes and their administration with LLC or MCN induced Th1 immune response. In addition, vaccine candidates containing MCN provided high percentage of protection against B. melitensis and B. abortus infection. Our results provided support to previous reports indicating that MCNs are attractive adjuvants and addition of this adjuvant to multi-epitopes antigens play an important role in the development of vaccine against Brucella.

Brucella antigens (BhuA, 7α-HSDH, FliC) in poly I:C adjuvant as potential vaccine candidates against brucellosis.

A promising strategy for controlling animal brucellosis is vaccination with commercial vaccine strains (Brucella melitensis Rev.1 and Brucella abortus RB51). Owing to safety concerns associated with these vaccines, developing a more effective and safe vaccine is essential. In this study, we examined the capacity of BhuA, 7α-HSDH or FliC antigens in the presence or absence of adjuvant in eliciting immune responses against brucellosis. After cloning, expression and purification, these proteins were used to examine immunologic responses. All immunized mice induced a vigorous IgG, with a predominant IgG2a response. Moreover, splenocytes of immunized mice proliferated and produced IL-2 and IFN-γ, suggesting the induction of cellular immunity. The high IgG2a/IgG1 ratio and IL-2 and IFN-γ indicated a Th1-oriented immune response in test groups. BhuA-, 7α-HSDH- or FliC- poly I:C formulations were the most effective at inducing Th1 immune response compared to groups immunized with naked proteins. Immunization with proteins protected mice against B. melitensis 16M and B. abortus 544. The proteins in adjuvant induced higher levels of protection than proteins only and exhibited similar degree of protection to live attenuated vaccines. Our results, for first time, introduced five potential candidates for subunit vaccine development against B. melitensis and B. abortus infection.

Nanoparticle-Based Vaccines for Brucellosis: Calcium Phosphate Nanoparticles-Adsorbed Antigens Induce Cross Protective Response in Mice.

INTRODUCTION: Vaccine formulation with appropriate adjuvants is an attractive approach to develop protective immunity against pathogens. Calcium phosphate nanoparticles (CaPNs) are considered as ideal adjuvants and delivery systems because of their great potential for enhancing immune responses. In the current study, we have designed nanoparticle-based vaccine candidates to induce immune responses and protection against B. melitensis and B. abortus. MATERIALS AND METHODS: For this purpose, we used three Brucella antigens (FliC, 7α-HSDH, BhuA) and two multi-epitopes (poly B and poly T) absorbed by CaPNs. The efficacy of each formulation was evaluated by measuring humoral, cellular and protective responses in immunized mice. RESULTS: The CaPNs showed an average size of about 90 nm with spherical shape and smooth surface. The CaPNs-adsorbed proteins displayed significant increase in cellular and humoral immune responses compared to the control groups. In addition, our results showed increased ratio of specific IgG2a (associated with Th1) to specific IgG1 (associated with Th2). Also, immunized mice with different vaccine candidate formulations were protected against B. melitensis 16M and B. abortus 544, and showed same levels of protection as commercial vaccines (B. melitensis Rev.1 and B. abortus RB51) except for BhuA-CaPNs. DISCUSSION: Our data support the hypothesis that these antigens absorbed with CaPNs could be effective vaccine candidates against B. melitensis and B. abortus.

Mannosylated chitosan nanoparticles loaded with FliC antigen as a novel vaccine candidate against Brucella melitensis and Brucella abortus infection.

Brucellosis is a worldwide bacterial zoonosis disease. Live attenuated Brucella vaccines have several drawbacks. Thus development of a safe and effective vaccine for brucellosis is a concern of many scientists. FliC protein contributes in virulence of Brucella; hence, it is a promising target for brucellosis vaccine. In this study, Mannosylated Chitosan Nanoparticles (MCN) loaded with FliC protein were synthesized as a targeted vaccine delivery system. The immunogenicity and protective efficacy of FliC and FliC-MCN against Brucella infection were evaluated in BALB/c mice. After cloning, expression and purification, FliC protein was loaded on MCN. The particle size, loading efficiency and in vitro release of the NPs were determined. Our investigation revealed that FliC and FliC-MCN could significantly increase specific IgG response (higher IgG2a titers). Besides, spleen cells from immunized mice produced high level of IFN-γ and IL-2 and low level IL-10 cytokines. Immunization with FliC and FliC-MCN conferred significant degree of protection against B. melitensis 16 M and B. abortus 544 infections. Overall these results indicate that FliC protein would be a novel potential antigen candidate for the development of a subunit vaccine against B. melitensis and B. abortus. Moreover, MCN could be used as an adjuvant and targeted vaccine delivery system.

Evaluation of immunogenicity of novel multi-epitope subunit vaccines in combination with poly I:C against Brucella melitensis and Brucella abortus infection.

Brucellosis is a worldwide zoonotic disease affecting domestic animals and humans. Due to several safety problems associated with live attenuated vaccines (Rev1 and RB51), it is necessary to produce an efficient and safer vaccine against Brucella. In this study, we evaluated efficacy of two novel multi-peptide vaccine candidates of FliC, 7α-HSDH, BhuA antigens with and without poly I:C adjuvant. Hence, humoral and cellular immune responses and protective efficacy were determined in immunized mice. Our investigation indicated that multi-epitope antigens showed a significant induction of Th1 immunity with high levels of specific IgG (especially the IgG2a), as well as IFN-γ and IL-2 compared to the control group. The addition of poly I:C to multi-epitope antigens improved the humoral and cellular immune responses. The multi-epitope antigens with and without poly I:C also provided cross protection against B. melitensis16M and B. abortus544 infections. The present study suggests that the novel multi-epitope vaccine candidates based on B cell, CD4+ and CD8+T-cell epitopes of FliC, 7α-HSDH, BhuA proteins would be potential vaccine candidate against B. melitensis and B. abortus infections. Furthermore, poly I:C could be considered as a strong Th1-inducing adjuvant in designing vaccine formulation against brucellosis.

Upregulation of MiR-122 via Trichostatin A Treatments in Hepatocyte-like Cells Derived from Mesenchymal Stem Cells.

The miR-122 is a tissue-specific miRNA; its expression is abundant in liver. MiR-122 upregulation is crucial for differentiation, functionality, and maintenance of differentiated phenotype in hepatocytes. The improving effects of trichostatin A (TSA) on hepatic differentiation have been reported previously. The aim of this study was to determine whether TSA can affect the expression of miR-122 in hepatocyte-like cells (HLCs) generated from human adipose tissue-derived mesenchymal stem cells (hAT-MSCs). The hepatic differentiation of hAT-MSCs induced by a mixture of growth factors and cytokines either with or without TSA treatments. The functionality of HLCs generated with or without TSA and the expression levels of miR-122 were studied. The expression levels of miR-122 in TSA-treated HLCs was significantly (p < 0.05) higher than those generated by growth factors and cytokines, only. The downregulation of a-fetoprotein (AFP) levels but enhanced albumin synthesis (p < 0.05) and upregulation of liver-enriched transcription factors (LETFs) HNF4α (hepatocyte nuclear factor 4α) and HNF6 (hepatocyte nuclear factor 6) were observed in TSA-treated HLCs (p < 0.05). In conclusion, administration of TSA in hepatogenic differentiation of hAT-MSCs resulted in higher expression levels of miR-122, facilitation of differentiation, and subsequently attenuation of AFP levels.

Molecular target therapy of AKT and NF-kB signaling pathways and multidrug resistance by specific cell penetrating inhibitor peptides in HL-60 cells.

BACKGROUND: PI3/AKT and NF-kB signaling pathways are constitutively active in acute myeloid leukemia and cross-talk between the two has been shown in various cancers. However, their role in acute myeloid leukemia has not been completely explored. We therefore used cell penetrating inhibitor peptides to define the contributions of AKT and NF-kB to survival and multi drug resistance (MDR) in HL-60 cells. MATERIALS AND METHODS: Inhibition of AKT and NF-kB activity by AKT inhibitor peptide and NBD inhibitor peptide, respectively, resulted in decreased expression of mRNA for the MDR1 gene as assessed by real time PCR. In addition, treatment of HL-60 cells with AKT and NBD inhibitor peptides led to inhibition of cell viability and induction of apoptosis in a dose dependent manner as detected by flow cytometer. RESULTS: Finally, co-treatment of HL-60 cells with sub-optimal doses of AKT and NBD inhibitor peptides led to synergistic apoptotic responses in AML cells. CONCLUSIONS: These data support a strong biological link between NF-kB and PI3-kinase/AKT pathways in the modulation of anti- apoptotic and multi drug resistant effects in AML cells. Synergistic targeting of these pathways using NF-kB and PI3-kinase/AK inhibitor peptides may have a therapeutic potential for AML and possibly other malignancies with constitutive activation of these pathways.