IL-23 receptor signaling licenses group 3-like innate lymphoid cells to restrict a live-attenuated oral Chlamydia vaccine in the gut.

An IFNγ-susceptible mutant of Chlamydia muridarum is attenuated in pathogenicity in the genital tract and was recently licensed as an intracellular Oral vaccine vector or intrOv. Oral delivery of intrOv induces transmucosal protection in the genital tract, but intrOv itself is cleared from the gut (without shedding any infectious particles externally) by IFNγ from group 3-like innate lymphoid cells (ILC3s). We further characterized the intrOv interactions with ILC3s in the current study, since the interactions may impact both the safety and efficacy of intrOv as an oral Chlamydia vaccine. Intracolonic inoculation with intrOv induced IFNγ that in return inhibited intrOv. The intrOv-IFNγ interactions were dependent on RORγt, a signature transcriptional factor of ILC3s. Consistently, the transfer of oral intrOv-induced ILC3s from RORγt-GFP reporter mice to IFNγ-deficient mice rescued the inhibition of intrOv. Thus, IFNγ produced by intrOv-induced ILC3s is likely responsible for inhibiting intrOv, which is further supported by the observation that oral intrOv did induce significant levels of IFNγ-producing LC3s (IFNγ+ILC3s). Interestingly, IL-23 receptor knockout (IL-23R-/-) mice no longer inhibited intrOv, which was accompanied by reduced colonic IFNγ. Transfer of oral intrOv-induced ILC3s rescued the IL-23R-/- mice to inhibit intrOv, validating the dependence of ILC3s on IL-23R signaling for inhibiting intrOv. Clearly, intrOv induces intestinal IFNγ+ILC3s for its own inhibition in the gut, which is facilitated by IL-23R signaling. These findings have provided a mechanism for ensuring the safety of intrOv as an oral Chlamydia vaccine and a platform for investigating how oral intrOv induces transmucosal protection in the genital tract.

Effect of Hydroxyethyl starch (HES) versus 5% albumin solution on intra-abdominal pressure in severe burn patients: A prospective randomized clinical trial.

INTRODUCTION: Massive burn patients are at risk of developing intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) as a complication of resuscitation. OBJECTIVE: This study aimed to evaluate the effect of Hydroxyethyl starch (HES) versus 5% albumin solution on intra-abdominal pressure (IAP) in massive burn patients. METHODS: This was a prospective randomized clinical trial carried on at Ain Shams University (ASU) burn unit for 2 years. Where adult patients with burns more than 20% of TBSA were equally randomized into HES group or albumin group. RESULTS: Fifty-two patients were equally randomized into 2 groups. We found no difference in age, sex, weight, type of burn, and TBSA between the two groups. The mean total resuscitation fluid volume in the first 48 h was 213 ml/kg and 206.2 ml/kg for the HES group and the albumin group respectively (p = 0.674). IAP statistically was non-significantly higher in the HES group. We found no statistical difference between the two groups as regards the renal function tests. CONCLUSION: Both HES and 5% albumin solution are effective and safe colloids for burn resuscitation. As regards the IAP, it seems that both 5% albumin and HES have comparable effect regarding IAH in severely burn patients. Both HES and 5% albumin were partially equal in terms of renal involvement and vital data stability.

Parietin Cyclodextrin-Inclusion Complex as an Effective Formulation for Bacterial Photoinactivation.

Multidrug resistance in pathogenic bacteria has become a significant public health concern. As an alternative therapeutic option, antimicrobial photodynamic therapy (aPDT) can successfully eradicate antibiotic-resistant bacteria with a lower probability of developing resistance or systemic toxicity commonly associated with the standard antibiotic treatment. Parietin (PTN), also termed physcion, a natural anthraquinone, is a promising photosensitizer somewhat underrepresented in aPDT because of its poor water solubility and potential to aggregate in the biological environment. This study investigated whether the complexation of PTN with (2-hydroxypropyl)-ß-cyclodextrin (HP-ß-CD) could increase its solubility, enhance its photophysical properties, and improve its phototoxicity against bacteria. At first, the solubilization behavior and complexation constant of the PTN/HP-ß-CD inclusion complexes were evaluated by the phase solubility method. Then, the formation and physicochemical properties of PTN/HP-ß-CD complexes were analyzed and confirmed in various ways. At the same time, the photodynamic activity was assessed by the uric acid method. The blue light-mediated photodegradation of PTN in its free and complexed forms were compared. Complexation of PTN increased the aqueous solubility 28-fold and the photostability compared to free PTN. PTN/HP-ß-CD complexes reduce the bacterial viability of Staphylococcus saprophyticus and Escherichia coli by > 4.8 log and > 1.0 log after irradiation, respectively. Overall, the low solubility, aggregation potential, and photoinstability of PTN were overcome by its complexation in HP-ß-CD, potentially opening up new opportunities for treating infections caused by multidrug-resistant bacteria.

Potent Cytotoxicity of Four Cameroonian Plant Extracts on Different Cancer Cell Lines.

In this study, the potential cytotoxicity of four plant extracts originated from Cameroon: Xylopia aethiopica (XA), Imperata cylindrica (IC), Echinops giganteus (EG) and Dorstenia psilurus (DP) were examined in vitro. We tested the anti-proliferative activity of the methanolic extracts of these compounds using MTT assay on seven different human cancer cell lines: HeLa, MDA-MB-231, A549, HepG2, U-87, SK-OV-3 and HL60. Induction of cell death was assessed by cell cycle analysis, apoptosis was determined by Annexin V-FITC binding and caspase 3/7 activity. As well, changes in mitochondrial membrane potential (MMP) and cell migration were tested. The genetic toxicity, using the alkaline comet assay, was evaluated. The studied extracts inhibited the cell proliferation of all tested cancer cell lines with concentration dependent effect over time. All of these extracts mainly induced apoptosis of HeLa cells by the accumulation of hypodiploid cells in the sub-G0/G1 phase and increasing the activity of caspase 3/7, as well they showed potential MMP disturbance and expressed a marked inhibitory effect on cell migration. Assessment of probable genetic toxicity by these extracts revealed no or minimum incidence of genetic toxicity. Therefore, the studied plant extracts are exhibiting potent anticancer activity based upon marked induction of tumor-cell death.