Prognostic Performance of Cystatin C in COVID-19: A Systematic Review and Meta-Analysis.

Cystatin C is a specific biomarker of kidney function. We perform this meta-analysis to determine the association of Cystatin C with the COVID-19 severity. In this systematic review and meta-analysis, we searched PubMed, EMBASE, Cochrane library, and Web of Science for studies published until 2nd September 2022 that reported associations between Cystatin C levels and COVID-19 severity. The analysis was performed using a random-effects model to calculate pooled standard mean difference (SMD). Twenty-five studies were included in the meta-analysis. Pooled analysis showed statistically significant differences of Cystatin C levels among survive vs. decreased patients (0.998 ± 0.225 vs. 1.328 ± 0.475 mg/dL, respectively; SMD = -2.14; 95%CI: -3.28 to -1.01; p < 0.001). Cystatin C levels in COVID-19 severe vs. non-severe groups varied and amounted to 1.485 ± 1.191 vs. 1.014 ± 0.601 mg/dL, respectively (SMD = 1.81; 95%CI: 1.29 to 2.32; p < 0.001). Additionally, pooled analysis showed that Cystatin C levels in patients with acute kidney injury (AKI) was 1.562 ± 0.885 mg/dL, compared to 0.811 ± 0.108 mg/dL for patients without AKI (SMD = 4.56; 95%CI: 0.27 to 8.85; p = 0.04). Summing up, Cystatin C is a potentially very good marker to be used in the context of COVID-19 disease due to the prognosis of patients' serious condition, risk of AKI and mortality. In addition, Cystatin C could be used as a marker of renal complications in COVID-19 other than AKI due to the need to monitor patients even longer after leaving the hospital.

Initial Evaluation of Uroplakins UPIIIa and UPII in Selected Benign Urological Diseases.

BACKGROUND: Uroplakins (UPs) are glycoproteins that play a specific role in the structure and function of the urothelium. Disorders which affect the normal expression of UPs are associated with the pathogenesis of infections and neoplasms of the urinary tract, primary vesicoureteral reflux, hydronephrosis and renal dysfunction. The appearance of uroplakins in the urine and/or plasma may be of potential importance in the detection of urinary tract dysfunction. The aim of the present study was to investigate uroplakin IIIa (UPIIIa) and uroplakin II (UPII) expression in patients with selected urological diseases. METHODS: Plasma and urine from patients with benign prostatic hyperplasia (BPH), urethral stricture (US), urinary tract infection (UTI) and urolithiasis were compared to healthy people without urological disorders. UPs concentrations were measured by the immunoenzymatic method. RESULTS: In patients with BPH and UTI, concentrations of UPIIIa in urine and plasma, as well as UPII in urine, were statistically significantly higher than in the control groups. In the US group, only the plasma UPIIIa concentration differed significantly from the control. CONCLUSION: The conducted research shows that benign urological diseases may affect the state of the urothelium, as manifested by increased concentrations of both UPs in patients' urine and plasma, especially in BPH and UTI.

The Dependence between Urinary Levels of Angiogenesis Factors, 8-Iso-prostaglandin F2α, É£-Synuclein, and Interleukin-13 in Patients with Bladder Cancer: A Pilot Study.

During the last decade, a significant increase in the incidence of bladder cancer (BC) has been observed. Angiogenesis plays a key role in the process of tumor growth and metastasis. Additionally, the participation of oxidative stress and chronic inflammation in BC pathogenesis is indicated. The aim of the study was to evaluate the urinary levels of parameters of angiogenesis, stimulating angiogenin (ANG) and inhibiting angiostatin (ANGST), 8-iso-prostaglandin F2α (8-iso-PGF2α) as a marker of oxidative stress, É£-synuclein (SNCG) as a cancer progression parameter, and interleukin-13 (IL-13) as an anti-inflammatory immunomodulator. The levels of ANG, ANGST, 8-iso-PGF2α, SNCG, and IL-13 in the urine of BC patients and healthy controls were measured by the enzyme-linked immunosorbent assay. These parameters were examined in the whole group of BC patients and in subgroups depending on the clinical stage: nonmuscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC); histopathologic malignancy: low grade (LG) and high grade (HG) and in primary and recurrent BC. Significantly, higher urinary parameters were found in BC patients in comparison to controls. Levels of all parameters increased with the development of cancer, with the exception of 8-iso-prostaglandin F2α, in which the level was higher in the early stages of the disease, but these differences were not statistically significant. Some correlations have been demonstrated between parameters in BC patients. Based on the receiver operating characteristic curves, ANG and ANGST had the best diagnostic value for BC. The obtained results indicate the important role of the examined parameters of angiogenesis, oxidative stress, and inflammation in the pathogenesis and development of BC. It is reasonable to continue research in order to thoroughly assess the impact of various associated processes on the course of BC. It is also important to carry out similar tests in patients with other urological diseases.

Chemical Synthesis of Oligoribonucleotide (ASL of tRNALys T.†brucei) Containing a Recently Discovered Cyclic Form of 2-Methylthio-N6 -threonylcarbamoyladenosine (ms2 ct6 A).

The synthesis of the protected form of 2-methylthio-N6 -threonylcarbamoyl adenosine (ms2 t6 A) was developed starting from adenosine or guanosine by using the optimized carbamate method and, for the first time, an isocyanate route. The hypermodified nucleoside was subsequently transformed into the protected ms2 t6 A-phosphoramidite monomer and used in a large-scale synthesis of the precursor 17nt ms2 t6 A-oligonucleotide (the anticodon stem and loop fragment of tRNALys from T. brucei). Finally, stereochemically secure ms2 t6 A→ms2 ct6 A cyclization at the oligonucleotide level efficiently afforded a tRNA fragment bearing the ms2 ct6 A unit. The applied post-synthetic approach provides two sequentially homologous ms2 t6 A- and ms2 ct6 A-oligonucleotides that are suitable for further comparative structure-activity relationship studies.

Are There Differences in Toxicity and Efficacy between Various Bacillus Calmette-Guerin Strains in Bladder Cancer Patients? Analysis of 844 Patients.

PURPOSE: To evaluate if there are differences in toxicity and efficacy between different Bacillus Calmette-Guerin (BCG) stains used for intravesical immunotherapy in patients with non-muscle invasive bladder cancer. METHODS: We retrospectively analysed a group of 844 patients who received TICE, RIVM and Moreau BCG strains. The allocation of the strain to each patient was random, stemming from differences in supply and distribution. The patients were analysed in terms of toxicity, recurrence-free (RFS), progression-free (PFS), cancer-specific (CSS) and overall survival (OS). RESULTS: In the survival analysis, statistical significance was not reached in any tumour group for any clinical event. TICE caused more local and mild adverse effects and severe complications were mainly associated with RIVM strain. In a group in which the strain was changed during the course of the therapy, significantly more severe complications were observed and, in most of these cases, complications appeared right after the strain change. CONCLUSIONS: There were no differences in terms of RFS, PFS, CSS and OS after use of TICE, RIVM and Moreau strains. The complication profile differed statistically between used strains with TICE causing mostly mild complications. Also, strain change during the therapy course was associated with the increased risk of moderate to severe toxicity occurrence.

Efficient conversion of N6-threonylcarbamoyladenosine (t6A) into a tRNA native hydantoin cyclic form (ct6A) performed at nucleoside and oligoribonucleotide levels.

A t6A nucleoside was efficiently and stereospecifically transformed into a hydantoin cyclic form of N6-l-threonylcarbamoyladenosine (ct6A) by the use of polymer bounded carbodiimide (EDC-P) and HOBt. The procedure was successfully applied for a post-synthetic conversion of t6A-containing RNA 17-mers (of the sequences of anticodon stem and loop (ASL) fragments of S. pombe tRNAi and E. coli tRNALys) into the products bearing the ct6A unit.

A hydantoin isoform of cyclic N6-threonylcarbamoyladenosine (ct6A) is present in tRNAs.

N6-Threonylcarbamoyladenosine (t6A) and its derivatives are universally conserved modified nucleosides found at position 37, 3΄ adjacent to the anticodon in tRNAs responsible for ANN codons. These modifications have pleiotropic functions of tRNAs in decoding and protein synthesis. In certain species of bacteria, fungi, plants and protists, t6A is further modified to the cyclic t6A (ct6A) via dehydration catalyzed by TcdA. This additional modification is involved in efficient decoding of tRNALys. Previous work indicated that the chemical structure of ct6A is a cyclic active ester with an oxazolone ring. In this study, we solved the crystal structure of chemically synthesized ct6A nucleoside. Unexpectedly, we found that the ct6A adopted a hydantoin isoform rather than an oxazolone isoform, and further showed that the hydantoin isoform of ct6A was actually present in Escherichia coli tRNAs. In addition, we observed that hydantoin ct6A is susceptible to epimerization under mild alkaline conditions, warning us to avoid conventional deacylation of tRNAs. A hallmark structural feature of this isoform is the twisted arrangement of the hydantoin and adenine rings. Functional roles of ct6A37 in tRNAs should be reconsidered.

Identification of 2-methylthio cyclic N6-threonylcarbamoyladenosine (ms2ct6A) as a novel RNA modification at position 37 of tRNAs.

Transfer RNA modifications play pivotal roles in protein synthesis. N6-threonylcarbamoyladenosine (t6A) and its derivatives are modifications found at position 37, 3΄-adjacent to the anticodon, in tRNAs responsible for ANN codons. These modifications are universally conserved in all domains of life. t6A and its derivatives have pleiotropic functions in protein synthesis including aminoacylation, decoding and translocation. We previously discovered a cyclic form of t6A (ct6A) as a chemically labile derivative of t6A in tRNAs from bacteria, fungi, plants and protists. Here, we report 2-methylthio cyclic t6A (ms2ct6A), a novel derivative of ct6A found in tRNAs from Bacillus subtilis, plants and Trypanosoma brucei. In B. subtilis and T. brucei, ms2ct6A disappeared and remained to be ms2t6A and ct6A by depletion of tcdA and mtaB homologs, respectively, demonstrating that TcdA and MtaB are responsible for biogenesis of ms2ct6A.

Uroplakins and their potential applications in urology.

INTRODUCTION: Urothelium is a highly specialized type of epithelium covering the interior of the urinary tract. One of the structures responsible for its unique features are urothelial plaques formed from glycoprotein heteropolymers, the uroplakins. Four types of uroplakins are known - UPIa, UPIb, UPII, UPIII. Herein we review the current status of knowledge about uroplakins and discuss their potential clinical applications. MATERIAL AND METHODS: A PubMed search was conducted to find original and review papers about uroplakins. RESULTS: Uroplakins can be detected in tissue, urine and blood. The process of urothelial plaque formation is complex and its disturbances resulting in incorrect plaque formation might be responsible for some pathological states. Additionally, uroplakins might be associated with other pathological processes i.e. urothelial cancer or infections of the urinary tract. CONCLUSIONS: Uroplakins as the end-product of urothelial cells have unique features and a complex structure. These glycoproteins can be involved in some diseases of the urinary tract and as such can be used as potential targets for intervention and markers of the disease.

Review of current optical diagnostic techniques for non-muscle-invasive bladder cancer.

INTRODUCTION: Urinary bladder urothelial cell carcinoma is one of the most commonly diagnosed cancers in Europe. After prostate, lung and colon cancers, bladder cancer rates as the fourth most common cancer in men in the world. Urinary bladder cancer detection, treatment, and staging have traditionally been based on an endoscopic examination - cystoscopy. MATERIAL AND METHODS: A Medline, and Web of Science database search was performed on September 2015 without setting time limits, using the terms 'bladder cancer' in conjunction with 'cystoscopy', 'diagnosis', 'detection', 'fluorescence', 'blue-light', 'PDD', 'narrow band imaging', 'molecular imaging', 'optical coherence tomography' or 'confocal laser endomicroscopy'. RESULTS: The new imaging techniques can be classified according to their scope as macroscopic, microscopic, and molecular. Macroscopic techniques, such as narrow band imaging, are similar to white light cystoscopy; however, they help visualize even very minute lesions in the bladder mucosa by means of contrast enhancement. Microscopic imaging techniques, such as optical coherence tomography and confocal laser endomicroscopy, provide high-resolution cross-sectional views of vesicular tissues, which resemble images obtained by histopathological examination. Therefore, these are referred as 'optical biopsy'. Molecular imaging methods offer highly specific real-time visualization of cancer cells and their differentiation from healthy tissue, by combining optical imaging with fluorescent labeling of elements such as antibodies. CONCLUSIONS: In this article we present a review of studies and literature concerning modern optical diagnostic techniques for non-muscle-invasive bladder cancer. We present available technology with its advantages and disadvantages, and studies regarding its effectiveness.

Patient comfort during flexible and rigid cystourethroscopy.

INTRODUCTION: Cystourethroscopy (CS) is an endoscopic method used to visualize the urethra and the bladder. AIM: In this study, we prospectively evaluated pain in men undergoing cyclic cystoscopic assessment with rigid and flexible instruments after transurethral resection of bladder tumor (TURB). MATERIAL AND METHODS: One hundred and twenty male patients who were under surveillance after a TURB procedure due to urothelial cell carcinoma and who had undergone at least one rigid cystourethroscopy in the past were enrolled in the trial. Patients were prospectively randomized to age-matched groups for flexible (group F) or rigid (group R) CS. Patient's comfort was evaluated on an 11-grade scale, ranging from 0 (free from pain) to 10 points (unbearable pain). RESULTS: The patients described the pain during the previous rigid CS as ranging from 4 to 10 (mean: 6.8) in group F and from 0 to 10 (mean: 5.8) in group R. Group R patients described the pain during the current rigid CS as ranging from 0 to 10 (mean: 5.7). No mean change in the grade was observed between the two pain descriptions (no change 11 patients, weaker pain 25 patients, stronger pain 24 patients, gamma 0.51, p < 0.0001). Group F described the pain as 1 to 5 (mean: 2.1). In the case of flexible CS the pain experience was greatly lowered compared to the previous rigid CS. All flexible CS patients reported lowered pain (by 1 to 9 grades). Patients' age did not influence the comfort of the flexible CS or the change in pain level. CONCLUSIONS: Flexible CS is better tolerated than rigid cystoscopy by male patients regardless of patients' age.

Stability studies on the newly discovered cyclic form of tRNA N(6)-threonylcarbamoyladenosine (ct(6)A).

A cyclic form of N(6)-threonylcarbamoyladenosine bearing an oxazolone moiety (ct(6)A) was discovered very recently at the position 37 in several tRNA sequences. Our study on the synthesized 5',3',2'-O-acetylated derivative of ct(6)A confirmed high stability of the modified nucleoside under physiological conditions (PBS buffer, pH 7.4) and revealed remarkable stability of the oxazolone ring in acidic (100mM HCl, pH 1) and basic (0.1mM NaOH, pH 10) conditions. This feature may allow for the post-synthetic conversion of t(6)A into ct(6)A in assembled oligoribonucleotides.