B7 immune checkpoint family members as putative therapeutics in autoimmune disease: An updated overview.

Autoimmune diseases, especially among young people in the US, are one of the leading causes of morbidity and death. The immune responses are the fundamental pathogenicity of autoimmune disorders. The equilibrium between stimulatory and inhibitory signals is critical for the stimulation, migration, survival, and T cell-related immune responses. The B7 family can substantially regulate T cell-mediated immune responses. Nevertheless, recent breakthroughs in immune checkpoint blockade in cancer immunotherapy have facilitated autoimmune diseases, especially among the prone populations. In the current study, we tried to concisely review the role of the B7 family in regulating immune reactions and the influence of immune checkpoint inhibitors on autoimmunity development.

Effect of TiO2 NPs on the growth, anatomic features and biochemistry parameters of Baby sun rose (Aptenia cordifolia).

Rapid commercialization, industrialization and the use of nanotechnology has led to an increase in the distribution of nanoparticles (NPs) in the environment. The most common metal oxide NPs which is present within products is Titanium dioxide (TiO2). TiO2 NPs have photocatalytic nature and can affect plant growth. The current study investigated the morphological, anatomical and biochemical features of Baby sun rose (Aptenia cordifolia) after exposure to different concentrations of TiO2 nanoparticles (0, 1, 5, 10 and 20 mg L-1). Treatment with TiO2 NPs showed changes in the morphological features and increased photosynthetic pigmentation within the plant. An increase in the level of phenolics (12%) and flavonoid compounds (13%) was observed when plants were treated with moderate levels of TiO2 NPs. A reduction in the diameter of the vascular bundles and increased thickening of the transverse wall were observed in several samples. The number of scattered vascular bundles in the stems increased. The morphological, biochemical, and anatomical responses of Baby sun rose indicates that plants can adapt to environments contaminated with up to 20 mg L-1 TiO2 NPs. The cultivation of Baby sun rose plants in environments polluted with TiO2 NPs is recommended. This study enhances the knowledge of the effect of TiO2 NPs on the growth of Baby sun rose which is an ornamental plant, widely cultivated in different regions of Iran. The results of this study suggest that contaminated environments up to 20 mg L-1 TiO2 NPs can be managed by phytoremediation. Further studies are needed to investigate this plant's tolerance strategies against stress caused by TiO2 NPs and bulk TiO2 as well as the effect of other nanoparticles on plant.

Characterization of Tigecycline Resistance Among Tigecycline Non-susceptible Klebsiella pneumoniae Isolates From Humans, Food-Producing Animals, and in vitro Selection Assay.

Emergence of extensively drug-resistant isolates of Klebsiella pneumoniae has prompted increased reliance on the last-resort antibiotics such as tigecycline (TGC) for treating infections caused by these pathogens. Consumption of human antibiotics in the food production industry has been found to contribute to the current antibiotic resistance crisis. In the current study, we aimed to investigate the mechanisms of TGC resistance among 18 TGC-non-susceptible (resistant or intermediate) K. pneumoniae (TGC-NSKP) isolates obtained from human (n = 5), food animals (n = 7), and in vitro selection experiment (n = 6). Isolates were genotyped by multilocus sequence typing (MLST). ramR, acrR, rpsJ, tetA, and mgrB (for colistin resistance) genes were sequenced. The presence of tetX, tetX1, and carbapenemase genes was examined by PCR. Susceptibility to different classes of antibiotics was evaluated by disc diffusion and broth macrodilution methods. The expression level of acrB was quantified by RT-qPCR assay. The 12 TGC-NSKP isolates [minimum inhibitory concentrations (MICs) = 4-32 mg/l] belonged to 10 distinct sequence types including ST37 (n = 2), ST11, ST15, ST45, ST1326 (animal isolates); ST147 (n = 2, human and animal isolates); and ST16, ST377, ST893, and ST2935 (human isolates). Co-resistance to TGC and colistin was identified among 57 and 40% of animal and human isolates, respectively. All human TGC-NSKP isolates carried carbapenemase genes (bla OXA - 48, bla NDM - 1, and bla NDM - 5). tetX/X1 genes were not detected in any isolates. About 83% of TGC-NSKP isolates (n = 15) carried ramR and/or acrR alterations including missense/nonsense mutations (A19V, L44Q, I141T, G180D, A28T, R114L, T119S, Y59stop, and Q122stop), insertions (positions +205 and +343), or deletions (position +205) for ramR, and R90G substitution or frameshift mutations for acrR. In one isolate ramR amplicon was not detected using all primers used in this study. Among seven colistin-resistant isolates, five harbored inactivated/mutated MgrB due to premature termination by nonsense mutations, insertion of IS elements, and frameshift mutations. All isolates revealed wild-type RpsJ and TetA (if present). Increased expression of acrB gene was detected among all resistant isolates, with the in vitro selected mutants showing the highest values. A combination of RamR and AcrR alterations was involved in TGC non-susceptibility in the majority of studied isolates.

Molecular epidemiology and nitrofurantoin resistance determinants of nitrofurantoin-non-susceptible Escherichia coli isolated from urinary tract infections.

OBJECTIVES: The worldwide emergence of multidrug-resistant uropathogens has resulted in the revival of old antibiotics such as nitrofurantoin (NIT) for the treatment of uncomplicated urinary tract infections (UTIs). This study aimed to identify determinants of NIT resistance and to investigate the genetic diversity of NIT-resistant (NIT-R) Escherichia coli isolates. METHODS: Six NIT-R and three NIT-susceptible clinical E. coli isolates from patients with UTI were studied. The susceptibility of the isolates to various classes of antibiotics was evaluated by disk diffusion. The presence of plasmid-encoded efflux pump genes (oqxA and oqxB) was investigated by PCR. Nucleotide sequences of the nfsA, nfsB and ribE genes were determined. The genetic relatedness of the NIT-R isolates was evaluated by multilocus sequence typing (MLST). RESULTS: All six NIT-R isolates were characterised with high-level NIT resistance (MIC ≥ 512 mg/L) and they belonged to five distinct STs including ST131 (n = 2), ST73, ST405, ST10 and ST354 (n = 1 each). Amikacin, carbapenems, minocycline, tigecycline and fosfomycin were the most active agents against the studied uropathogens. The oqxA and oqxB genes were not detected in any isolate. All NIT-R isolates harboured inactivating genetic alterations in nfsA and nfsB [NfsA H11Y, S33N, S38Y, W212R substitutions, Δg638 (frameshift), Δa64-g73 (frameshift) and NfsB F84S, P45S, W94Stop, E197Stop substitutions, ΔnfsB locus]. The ribE gene of most isolates was unaffected, except for one isolate co-harbouring a deleterious RibE G85C substitution and NfsA/B alterations. CONCLUSION: NIT resistance in the studied E. coli isolates was mainly mediated by nfsA and nfsB alterations.

Biological activity of the Agrobacterium rhizogenes-derived trolC gene of Nicotiana tabacum and its functional relation to other plast genes.

Agrobacterium rhizogenes induces hairy roots through the activity of three essential T-DNA genes, rolA, rolB, and rolC, whereas the orf13 gene acts as an accessory root-inducing gene. rolB, rolC, and orf13 belong to the highly diverged plast gene family with remotely related representatives in the endomycorrhizal basidiomycete Laccaria bicolor. Nicotiana glauca and N. tabacum contain A. rhizogenes-derived T-DNAs with active plast genes. Here, we report on the properties of a rolC homolog in N. tabacum, trolC. Dexamethasone-inducible trolC and A4-rolC genes from A. rhizogenes A4 induce comparable, strong growth effects affecting all parts of the plants. Several have not been described earlier and were found to be very similar to the effects of the distantly related plast gene 6b. They include leaf chlorosis and starch accumulation, enations, increase of sucrose-dependent leaf disk expansion, growth of isolated roots on low-sucrose media, and stimulation of sucrose uptake by small root fragments. Collectively, our findings indicate that enhancement of sucrose uptake plays an important role in generating the complex 6b and rolC phenotypes and might be an ancestral property of the plast genes.