Integrative proteomics and bioinformatic prediction enable a high-confidence apicoplast proteome in malaria parasites.

Malaria parasites (Plasmodium spp.) and related apicomplexan pathogens contain a nonphotosynthetic plastid called the apicoplast. Derived from an unusual secondary eukaryote-eukaryote endosymbiosis, the apicoplast is a fascinating organelle whose function and biogenesis rely on a complex amalgamation of bacterial and algal pathways. Because these pathways are distinct from the human host, the apicoplast is an excellent source of novel antimalarial targets. Despite its biomedical importance and evolutionary significance, the absence of a reliable apicoplast proteome has limited most studies to the handful of pathways identified by homology to bacteria or primary chloroplasts, precluding our ability to study the most novel apicoplast pathways. Here, we combine proximity biotinylation-based proteomics (BioID) and a new machine learning algorithm to generate a high-confidence apicoplast proteome consisting of 346 proteins. Critically, the high accuracy of this proteome significantly outperforms previous prediction-based methods and extends beyond other BioID studies of unique parasite compartments. Half of identified proteins have unknown function, and 77% are predicted to be important for normal blood-stage growth. We validate the apicoplast localization of a subset of novel proteins and show that an ATP-binding cassette protein ABCF1 is essential for blood-stage survival and plays a previously unknown role in apicoplast biogenesis. These findings indicate critical organellar functions for newly discovered apicoplast proteins. The apicoplast proteome will be an important resource for elucidating unique pathways derived from secondary endosymbiosis and prioritizing antimalarial drug targets.

Comparison of the efficacy of the early LI-SWT plus daily tadalafil with daily tadalafil only as penile rehabilitation for postprostatectomy erectile dysfunction.

This study compares the efficacy of the early low-intensity shock wave therapy (LI-SWT) plus daily tadalafil with daily tadalafil only therapy as penile rehabilitation for postprostatectomy erectile dysfunction in patients with prostate cancer who underwent bilateral interfascial nerve-sparing radical prostatectomy (robotic or open). From April 2019 to March 2021, 165 patients were enrolled, and 80 of them successfully completed this prospective study. Daily tadalafil were administered to all the patients. LI-SWT consisted of a total of six sessions. Each session was performed on days 4, 5, 6, and 7, and on the second and fourth weeks after surgery. Each LI-SWT session consisted of 300 shocks at an energy density of 0.09 mJ/mm2 and a frequency of 120 shocks per minute that were delivered at each of the five treatment points for 15 min. Thirty-nine patients were treated with tadalafil-only (group A) while 41 were treated with tadalafil and LI-SWT simultaneously (group B). At postoperative 6 months, the proportion of patients with erection hardness scores (EHS) ≥ 3 (4/39 vs. 12/41) was significantly higher in group B (p = 0.034), and LI-SWT was the only independent factor for predicting EHS ≥ 3 (OR, 3.621; 95% CI, 1.054-12.437; p = 0.041). There were no serious side effects related to early LI-SWT. Early LI-SWT plus daily tadalafil therapy as penile rehabilitation for postprostatectomy erectile dysfunction is thought to be more efficacious than tadalafil only. Further large-scaled randomized controlled trials will be needed to validate these findings.

Should We Always Perform Preoperative Chest Computed Tomography in Patients with cT1a Renal Cell Carcinoma?

No definitive criteria regarding the performance of preoperative chest computed tomography (CT) in patients with cT1a renal cell carcinoma (RCC) exists. We aimed to establish an objective standard for the optimal timing of preoperative chest CT in patients with RCC. Data from 890 patients who underwent surgical treatment for RCC between January 2011 and December 2020 were retrospectively collected. The primary endpoint was detection of lung metastasis on chest CT before nephrectomy. A multivariable logistic regression model predicting positive chest CT scans was used. Predictors included preoperative cTN stage, presence of systemic symptoms, Charlson comorbidity index (CCI), platelet count/hemoglobin ratio, albumin/globulin ratio (AGR), and De Ritis ratio. The overall rate of positive chest CT scans before nephrectomy was 3.03% (27/890). Only one patient had lung metastasis before surgery for cT1a. cT stage (≥cT1b), CCI ≥4, and low AGR were associated with a higher risk of positive chest CT scans. The best cutoff value for AGR was 1.39. After 890-sample bootstrap validation, the concordance index was 0.80. The net benefit of the proposed strategy was superior to that of the select-all and select-none strategies according to decision curve analysis. Therefore, when chest CT scans were performed with a risk of a positive result ≥10%, 532 (59.8%) negative chest CT scans could be prevented. Only 24 (2.7%) potentially positive chest CT scans were misdiagnosed. Therefore, we recommend chest CT in patients with ≥cT1b disease, CCI ≥4, and low AGR.

Comparison of the Effect of Steroids on the Treatment of Phimosis according to the Steroid Potencies.

PURPOSE: This study aimed to evaluate the outcomes of topical steroid therapy according to potency as the first-line treatment for boys with symptomatic phimosis. MATERIALS AND METHODS: From April 2017 to March 2019, we retrospectively reviewed 45 boys with severe phimosis (Kikiros retractability grade 4 or 5) who presented with phimosis-related complications. During the first year of the study period, methylprednisolone aceponate (MPA, Advantan®, potent topical steroid) was administered in 24 boys. Hydrocortisone butyrate (HCB, Bandel®, moderately potent topical steroid) was administered in 21 boys in the subsequent period. Topical steroids were administered for 4-8 weeks in all patients. Success of the therapy was determined by two conditions at 3 months after therapy: achieving Kikiros grade 3 and less with disappearance of symptoms. RESULTS: Of 45 boys, 35 (77.8%) achieved success of the therapy. Mean age was 46.64±22.42 months. Recurrence of phimosis with clinical complications was confirmed in three of 35 patients with initial success (8.6%) during the follow-up period. All boys with recurrence showed remission after additional topical steroid therapy. Success rate of the MPA group was higher than that of the HCB group (91.7% and 61.9% respectively, P = .029). Side effects associated with the topical steroid application were not observed in all children. CONCLUSION: Topical steroid application is an effective and safe procedure as first-line treatment in symptomatic boys with severe phimosis. Moreover, the potency of topical steroids for the treatment of phimosis is considered a factor affecting the success rate.

Lysed and disrupted Bifidobacterium bifidum BGN4 cells promote anti-inflammatory activities in lipopolysaccharide-stimulated RAW 264.7 cells.

Bifidobacterium bifidum BGN4 has been shown to improve the immune system by regulating interleukin (IL)-6 in RAW 264.7 macrophage cells. In this study, the dead cells of B. bifidum BGN4 were produced by enzymatic and physical processing to enhance the inhibition properties of pro-inflammatory cytokines using lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Notably, the secretion levels of cytokines such as interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor (TNF)-α were decreased by the cell-wall disrupted extracts compared to heat-killed cells. The result suggests that the exposed interior-surface of B. bifidum BGN4 has a potential ability to regulate the immune-responses in the gastrointestinal tract due to major substances in inside-cell wall such as peptidoglycan and teichoic acids. In conclusion, the lysed and disrupted cells from the inside out of B. bifidum BGN4 have anti-inflammatory properties as paraprobiotic agents to control chronic inflammatory related-diseases.

Heterologous expression of Deinococcus geothermalis amylosucrase in Corynebacterium glutamicum for luteolin glucoside production.

Amylosucrase (ASase) has great industrial potential owing to its multifunctional activities, including transglucosylation, polymerization, and isomerization. In the present study, the properties of Deinococcus geothermalis ASase (DGAS) expressed in Corynebacterium glutamicum (cDGAS) and purified via Ni-NTA affinity chromatography were compared to those of DGAS expressed in Escherichia coli (eDGAS). The pH profile of cDGAS was similar to that of eDGAS, whereas the temperature profile of cDGAS was lower than that of eDGAS. The melting temperature of both enzymes did not differ significantly. Interestingly, polymerization activity was slightly lower in cDGAS than in eDGAS, whereas luteolin (an acceptor molecule) transglucosylation activity in cDGAS was 10 % higher than that in eDGAS. Analysis of protein secondary structure via circular dichroism spectroscopy revealed that cDGAS had a lower strand/helix ratio than eDGAS. The present results indicate that cDGAS is of greater industrial significance than eDGAS.

Enzymatic synthesis of α-flavone glucoside via regioselective transglucosylation by amylosucrase from Deinococcus geothermalis.

α-Flavone glycosides have beneficial properties for applications in the pharmaceutical, cosmetic, and food industries. However, their chemical syntheses are often limited by a low efficiency or scarcity of substrates. In this study, α-flavone glucosides were enzymatically synthesized by amylosucrase from Deinococcus geothermalis (DGAS) using sucrose and various flavones as a donor for glucosyl units and acceptors, respectively. Luteolin was the most effective acceptor in the transglucosylation reaction using DGAS among nine flavone materials (apigenin, chrysin, 6,7-dihydroxyflavone, homoorientin, 7-hydroxyflavone, isorhoifolin, luteolin, luteolin-3',7-diglucoside, and orientin). The highest production yield of luteolin glucoside was 86%, with a 7:1 molar ratio of donor to acceptor molecules, in 50 mM Tris-HCl buffer (pH 7) at 37°C for 24 h using 2 U of DGAS. The synthesized luteolin glucoside was identified as luteolin-4'-O-α-D-glucopyranoside with a glucose molecule linked to the C-4' position on the B-ring of luteolin via an α-glucosidic bond, as determined by 1H and 13C nuclear magnetic resonance. This result clearly confirmed that the glucosylated luteolin was successfully synthesized by DGAS and it can be applied as a functional ingredient. Furthermore, this approach using DGAS has the potential to be utilized for the synthesis of various glucosylated products using different types of polyphenols to enhance their functionalities.

Two Cases of Russell Body Gastritis Treated by Helicobacter pylori Eradication.

Russell body gastritis was first defined in 1998, but not many cases have been reported since then. The exact causes and process of this condition are unknown yet; however, considering the reported cases, it has been highly suggested to have correlation with Helicobacter pylori infection. Russell body gastritis has a non-specific clinical presentation of gastritis such as gastric mucosal edema in the macroscopic view. It can be mistaken as xanthoma, signet ring cell carcinoma, or a malignant lymphoma including mucosa-associated lymphoid tissue lymphoma and plasmocytoma. Russell body gastritis features polyclonal immunoglobulin and is differentiated from Mott cancer, of which immune globulin has monoclonal aspect. Authors report here two cases of Russell body gastritis with examined endoscopic findings as well as a review of related literature on the association of all reported cases of Russell body gastritis with H. pylori infection.