ABSTRACT
Mitochondria are essential organelles because they generate the energy required for cellular functions. Kidney stones, as one of the most common urological diseases, have garnered significant attention. In this study, we first collected peripheral venous blood from patients with kidney stones and used qRT-PCR to detect mitochondrial DNA (mtDNA) copy number as a means of assessing mitochondrial function in these patients. Subsequently, through Western blotting, qPCR, immunofluorescence, immunohistochemistry, and transmission electron microscopy, we examined whether calcium oxalate crystals could cause mitochondrial dysfunction in the kidney in both in vitro and in vivo. We then examined the intersection of the DEGs obtained by transcriptome sequencing of the mouse kidney stone model with mitochondria-related genes, and performed KEGG and GO analyses on the intersecting genes. Finally, we administered the mitochondrial ROS scavenger Mito-Tempo in vivo and observed its effects. Our findings revealed that patients with kidney stones had a reduced mtDNA copy number in their peripheral venous blood compared to the control group, suggesting mitochondrial dysfunction in this population. This conclusion was further validated through in vitro and in vivo experiments. Enrichment analyses revealed that the intersecting genes were closely related to metabolism. We observed that after mitochondrial function was preserved, the deposition of calcium oxalate crystals decreased, and the kidney damage and inflammation caused by them were also alleviated. Our research indicates that kidney stones can cause mitochondrial dysfunction. After clearing mtROS, the damage and inflammation caused by kidney stones are reversed, providing new insights into the prevention and treatment of kidney stones.
Subject(s)
Calcium Oxalate , DNA, Mitochondrial , Kidney Calculi , Mitochondria , Reactive Oxygen Species , Kidney Calculi/blood , Kidney Calculi/etiology , Humans , Animals , Mice , DNA, Mitochondrial/genetics , Mitochondria/metabolism , Calcium Oxalate/metabolism , Reactive Oxygen Species/metabolism , Male , Female , Mice, Inbred C57BL , Middle Aged , Disease Models, Animal , Kidney/pathology , Kidney/metabolism , Adult , Organophosphorus Compounds , PiperidinesABSTRACT
Rhizoma Polygonati (RP) is the dried rhizome of the liliaceous plant. It has anti-inflammatory and anti-apoptosis effects. But its role in kidney stones has not been studied. The purpose of this study was to verify the effect of RP in the treatment of nephrolithiasis through network pharmacological analysis and in vivo experiments. The active compounds and protein targets of RP, as well as the potential targets of the nephrolithiasis were searched from the database. The protein-protein interaction (PPI) network diagram and the drug-compounds-targets-disease network were constructed. The enrichment analysis was performed by Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, the effect of RP on the prevention and treatment of nephrolithiasis was experimentally validated in vivo. Animal experiments showed that RP ameliorates renal function and reduced crystal deposition in a mouse model. It may act through anti-inflammation and anti-apoptosis. Our study showed that RP could prevent and treat nephrolithiasis by inhibiting apoptosis and inflammation, which provided a new efficacy and clinical application for RP.
Subject(s)
Kidney Calculi , Network Pharmacology , Animals , Mice , Rhizome , Kidney Calculi/drug therapy , Apoptosis , Databases, FactualABSTRACT
BACKGROUND: Antibiotics biosynthesis is usually regulated by the cluster-situated regulatory gene(s) (CSRG(s)), which directly regulate the genes within the corresponding biosynthetic gene cluster (BGC). Previously, we have demonstrated that LmbU functions as a cluster-situated regulator (CSR) of lincomycin. And it has been found that LmbU regulates twenty non-lmb genes through comparative transcriptomic analysis. However, the regulatory mode of CSRs' targets outside the BGC remains unknown. RESULTS: We screened the targets of LmbU in the whole genome of Streptomyces lincolnensis and found fourteen candidate targets, among which, eight targets can bind to LmbU by electrophoretic mobility shift assays (EMSA). Reporter assays in vivo revealed that LmbU repressed the transcription of SLINC_0469 and SLINC_1037 while activating the transcription of SLINC_8097. In addition, disruptions of SLINC_0469, SLINC_1037, and SLINC_8097 promoted the production of lincomycin, and qRT-PCR showed that SLINC_0469, SLINC_1037, and SLINC_8097 inhibited transcription of the lmb genes, indicating that all the three regulators can negatively regulate lincomycin biosynthesis. CONCLUSIONS: LmbU can directly regulate genes outside the lmb cluster, and these genes can affect both lincomycin biosynthesis and the transcription of lmb genes. Our results first erected the cascade regulatory circuit of LmbU and regulators outside lmb cluster, which provides the theoretical basis for the functional research of LmbU family proteins.
Subject(s)
Bacterial Proteins , Streptomyces , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Lincomycin , Streptomyces/genetics , Streptomyces/metabolism , Transcriptome , Gene Expression Regulation, Bacterial , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/metabolismABSTRACT
BACKGROUND: Kidney stones account for a high proportion of urological emergencies. The main objective of this paper is to evaluate the predictive ability of five scoring systems for overall stone-free status and postoperative complications after percutaneous nephrolithotomy and retrograde ureteroscopy. MATERIALS AND METHODS: This study retrospectively analysed 312 cases of kidney stone patients between January 2021 and May 2022 at our centre. Multivariate logistic regression as well as ROC curves were applied to determine the ability to evaluate each scale to predict stone-free rates and postoperative complications. RESULTS: 179 patients have undergone PCNL. After multivariate logistic regression, the S.T.O.N.E score and history of ipsilateral renal surgery were predictive of stone-free status, and the predictive power of the S.T.O.N.E score was higher than that of history of ipsilateral renal surgery. Grade 1 complications were considered to be related to Guy's score and grade 2 complications were considered to be related to history of diabetes mellitus. 133 patients have undergone f-URS. After multivariate logistic regression analysis, the modified S-ReSC score, RUSS score, and R.I.R.S score were predictive of stone-free status, with the R.I.R.S score being the strongest predictor. Evidence of grade 2 complications was considered to be related to abnormal renal function. CONCLUSION: For PCNL, the S.T.O.N.E score had the best efficacy in predicting stone-free status, and the Guy's score had the best efficacy in predicting postoperative complications; for f-URS, the R.I.R.S score had the best efficacy in predicting stone-free status, and no scoring system predicted postoperative complications.
Subject(s)
Kidney Calculi , Nephrolithotomy, Percutaneous , Humans , Nephrolithotomy, Percutaneous/adverse effects , Treatment Outcome , Retrospective Studies , Ureteroscopy/adverse effects , Length of Stay , Operative Time , Kidney Calculi/complications , Postoperative Complications/epidemiology , Postoperative Complications/etiologyABSTRACT
Purpose: Severe hemorrhage after percutaneous nephrolithotomy (PCNL) is a rare but alerting event. In this study, we report the factors affecting massive hemorrhage after PCNL, various levels of vascular damage during renal angiography, and the therapeutic effect of superselective renal artery embolization (SRAE). Patients and Methods. A retrospective analysis was performed on the data of 69 patients with postoperative PCNL hemorrhage who underwent SRAE from January 2010 to March 2021. Inclusion criteria for all cases were failure of conservative treatment for severe renal hemorrhage after surgery and then treatment with SRAE. In addition, 98 patients without significant hemorrhage after PCNL were randomly selected as the control group. All clinical data are confirmed by imaging and laboratory examinations. We performed univariate and multivariate analyses to find risk factors of massive hemorrhage and high-grade renal vascular injury after PCNL. Results: A total of 69 patients underwent angiography, 64 of which received SRAE due to positive hemorrhages detected by angiography. Urinary tract infection (OR (95% CI) = 11.214 (2.804â¼44.842)), high blood pressure (OR (95% CI) = 5.686 (1.401â¼23.083)), and no hydronephrosis (OR (95% CI) = 0.189 (0.049â¼0.724)) are the most important factors leading to massive hemorrhage after PCNL. In patients who need SRAE after hemorrhage, high-grade vascular injury (grade III) is related to advanced age and decreased hemoglobin. Conclusion: During the perioperative period of PCNL, patients with a risk of hypertension, urinary tract infection, and no hydronephrosis should be strengthened to monitor their high risk of postoperative hemorrhage. For patients with postoperative hemorrhage, we can use the patient's age and decreased hemoglobin before and after operation for analysis. In this way, individualized assessment can greatly improve the efficiency of SRAE treatment.
Subject(s)
Kidney Calculi , Nephrolithotomy, Percutaneous , Urinary Tract Infections , Vascular System Injuries , Humans , Nephrolithotomy, Percutaneous/adverse effects , Vascular System Injuries/complications , Retrospective Studies , Postoperative Hemorrhage/etiology , Postoperative Hemorrhage/therapy , Urinary Tract Infections/etiology , Hemoglobins , Kidney Calculi/surgery , Treatment OutcomeABSTRACT
BACKGROUND: The outcomes of patients with tumors of the thoracolumbar spine treated with en bloc resection (EBR) using three-dimensional (3D)-printed endoprostheses are underreported. METHODS: We retrospectively evaluated patients with thoracolumbar tumors who underwent surgery at our institution. Logistic regression analysis was performed to identify the potential risk factors for surgical complications. Nomograms to predict complications were constructed and validated. RESULTS: A total of 53 patients with spinal tumors underwent EBR at our hospital; of these, 2 were lost to follow-up, 45 underwent total en bloc spondylectomy, and 6 were treated with sagittal en bloc spondylectomy. The anterior reconstruction materials included a customized 3D-printed artificial vertebral body (AVB) in 10 cases and an off-the-shelf 3D-printed AVB in 41 cases, and prosthesis mismatch occurred in 2 patients reconstructed with the off-the-shelf 3D-printed AVB. The median follow-up period was 21 months (range, 7-57 months). Three patients experienced local recurrence, and 5 patients died at the final follow-up. A total of 50 perioperative complications were encountered in 29 patients, including 25 major and 25 minor complications. Instrumentation failure occurred in 1 patient, and no prosthesis subsidence was observed. Using a combined surgical approach was a dependent predictor of overall complications, while Karnofsky performance status score, lumbar spine lesion, and intraoperative blood loss ≥ 2000 mL were predictors of major complications. Nomograms for the overall and major complications were constructed using these factors, with C-indices of 0.850 and 0.891, respectively. CONCLUSIONS: EBR is essential for the management of thoracolumbar tumors; however, EBR has a steep learning curve and a high complication rate. A 3D-printed AVB is an effective and feasible reconstruction option for patients treated with EBR.
Subject(s)
Spinal Neoplasms , Vertebral Body , Humans , Vertebral Body/pathology , Retrospective Studies , Spinal Neoplasms/surgery , Spinal Neoplasms/pathology , Treatment Outcome , Printing, Three-DimensionalABSTRACT
Regulators belonging to the DeoR family are widely distributed among the bacteria. Few studies have reported that DeoR family proteins regulate secondary metabolism of Streptomyces. This study explored the function of DeoR (SLINC_8027) in Streptomyces lincolnensis. Deletion of deoR in NRRL 2936 led to an increase in cell growth. The lincomycin production of the deoR deleted strain ΔdeoR was 3.4-fold higher than that of the wild strain. This trait can be recovered to a certain extent in the deoR complemented strain ΔdeoR::pdeoR. According to qRT-PCR analysis, DeoR inhibited the transcription of all detectable genes in the lincomycin biosynthesis cluster and repressed the expression of glnR, bldD, and SLCG_Lrp, which encode regulators outside the cluster. DeoR also inhibited the transcription of itself, as revealed by the XylE reporter. Furthermore, we demonstrated that DeoR bound directly to the promoter region of deoR, lmbA, lmbC-D, lmbJ-K, lmrA, lmrC, glnR, and SLCG_Lrp, by recognizing the 5'-CGATCR-3' motif. This study found that versatile regulatory factor DeoR negatively regulates lincomycin biosynthesis and cellular growth in S. lincolnensis, which expanded the regulatory network of lincomycin biosynthesis.
Subject(s)
Lincomycin , Streptomyces , Lincomycin/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Streptomyces/genetics , Streptomyces/metabolism , Secondary Metabolism , Gene Expression Regulation, BacterialABSTRACT
The majority of benign meningiomas exhibit a slow growth rate and are associated with a good prognosis. The recurrence and extracranial metastases of meningioma are rare. The present report describes the case of a patient with recurrence of transitional meningioma for which total resection had been performed 8 years prior. Furthermore, the transitional meningioma transformed into atypical meningioma, and metastasized to the ribs. The present report aimed to describe the clinical features and pathological findings of a case of malignant transformation and distant metastasis of benign meningioma. A review of the literature was also performed.
ABSTRACT
BACKGROUND: N6 -methyladenosine (m6A) is of great importance in renal physiology and disease progression, but its function and mechanism in renal fibrosis remain to be comprehensively and extensively explored. Hence, this study will explore the function and potential mechanism of critical regulator-mediated m6A modification during renal fibrosis and thereby explore promising anti-renal fibrosis agents. METHODS: Renal tissues from humans and mice as well as HK-2 cells were used as research subjects. The profiles of m6A modification and regulators in renal fibrosis were analysed at the protein and RNA levels using Western blotting, quantitative real-time polymerase chain reaction and other methods. Methylation RNA immunoprecipitation sequencing and RNA sequencing coupled with methyltransferase-like 3 (METTL3) conditional knockout were used to explore the function of METTL3 and potential targets. Gene silencing and overexpression combined with RNA immunoprecipitation were performed to investigate the underlying mechanism by which METTL3 regulates the Ena/VASP-like (EVL) m6A modification that promotes renal fibrosis. Molecular docking and virtual screening with in vitro and in vivo experiments were applied to screen promising traditional Chinese medicine (TCM) monomers and explore their mechanism of regulating the METTL3/EVL m6A axis and anti-renal fibrosis. RESULTS: METTL3 and m6A modifications were hyperactivated in both the tubular region of fibrotic kidneys and HK-2 cells. Upregulated METTL3 enhanced the m6A modification of EVL mRNA to improve its stability and expression in an insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)-dependent manner. Highly expressed EVL binding to Smad7 abrogated the Smad7-induced suppression of transforming growth factor-ß (TGF-ß1)/Smad3 signal transduction, which conversely facilitated renal fibrosis progression. Molecular docking and virtual screening based on the structure of METTL3 identified a TCM monomer named isoforsythiaside, which inhibited METTL3 activity together with the METTL3/EVL m6A axis to exert anti-renal fibrosis effects. CONCLUSIONS: Collectively, the overactivated METTL3/EVL m6A axis is a potential target for renal fibrosis therapy, and the pharmacological inhibition of METTL3 activity by isoforsythiaside suggests that it is a promising anti-renal fibrosis agent.
Subject(s)
Methyltransferases , RNA , Animals , Humans , Mice , Fibrosis , Methyltransferases/genetics , Methyltransferases/metabolism , Molecular Docking Simulation , RNA, Messenger/genetics , RNA-Binding ProteinsABSTRACT
AtrA belongs to the TetR family and has been well characterized for its roles in antibiotic biosynthesis regulation. Here, we identified an AtrA homolog (AtrA-lin) in Streptomyces lincolnensis. Disruption of atrA-lin resulted in reduced lincomycin production, whereas the complement restored the lincomycin production level to that of the wild-type. In addition, atrA-lin disruption did not affect cell growth and morphological differentiation. Furthermore, atrA-lin disruption hindered the transcription of regulatory gene lmbU, structural genes lmbA and lmbW inside the lincomycin biosynthesis gene cluster, and 2 other regulatory genes, adpA and bldA. Completement of atrA-lin restored the transcription of these genes to varying degrees. Notably, we found that AtrA-lin directly binds to the promoter region of lmbU. Collectively, AtrA-lin positively modulated lincomycin production via both pathway-specific and global regulators. This study offers further insights into the functional diversity of AtrA homologs and the mechanism of lincomycin biosynthesis regulation.
Subject(s)
Lincomycin , Streptomyces , Lincomycin/pharmacology , Lincomycin/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Streptomyces/genetics , Streptomyces/metabolism , Gene Expression Regulation, Bacterial , Anti-Bacterial Agents/metabolismABSTRACT
INTRODUCTION: Ureteral stents are commonly used in urology but are frequently associated with hematuria, abdominal discomfort, urinary tract infection, stent displacement, and stent encrustation. Surface modification of ureteral stents is beneficial to solve the problem, and these can be divided into coated stents and drug-eluting stents according to the modification method. Coated stents can be divided into hydrophilic coatings, antibacterial coatings, and anti-encrustation coatings. Drug-eluting stents can be divided into antimicrobial drug-eluting, antispasmodic analgesic drug-eluting, anti-ureteral stricture drug-eluting, and anti-tumor drug-eluting. Surface modification of ureteral stents can not only reduce complications related to ureteral stents but also strengthen the treatment of certain urologic diseases, which has a high clinical application value. AREAS COVERED: This review focuses on highlighting and summarizing the latest research progress about surface modification of ureteral stents, ureteral stent development history, classification, functions, and future development prospects. EXPERT OPINION: The purpose of this article is to discuss surface modification of ureteral stents to reduce stent-related complications and potential research directions for the treatment of urinary tract tumors are also briefly discussed, to help guide further innovation in ureteral stent coatings, which contribute to the future progress of ureteral stents surface modification.
Subject(s)
Drug-Eluting Stents , Ureter , Urinary Tract Infections , Humans , Stents , Ureter/surgery , Anti-Bacterial AgentsABSTRACT
Lincomycin is a broad-spectrum antibiotic and particularly effective against Gram-positive pathogens. Albeit familiar with the biosynthetic mechanism of lincomycin, we know less about its regulation, limiting the rational design for strain improvement. We therefore analyzed two-component systems (TCSs) in Streptomyces lincolnensis, and selected eight TCS gene(s) to construct their deletion mutants utilizing CRISPR/Cas9 system. Among them, lincomycin yield increased in two strains (Δ3900-3901 and Δ5290-5291) while decreased in other four strains (Δ3415-3416, Δ4153-4154, Δ4985, and Δ7949). Considering the conspicuous effect, SLINC_5291-5290 (AflQ1-Q2) was subsequently studied in detail. Its repression on lincomycin biosynthesis was further proved by gene complementation and overexpression. By binding to a 16-bp palindromic motif, the response regulator AflQ1 inhibits the transcription of its encoding gene and the expression of eight operons inside the lincomycin synthetic cluster (headed by lmbA, lmbJ, lmbK, lmbV, lmbW, lmbU, lmrA, and lmrC), as demonstrated by quantitative RT-PCR and electrophoretic mobility shift assays. Besides, the regulatory genes including bldD, glnR, lcbR1, and ramR are also regulated by the TCS. According to the screening towards nitrogen sources, aspartate affects the regulatory behavior of histidine kinase AflQ2. And in return, AflQ1 accelerates aspartate metabolism via ask-asd, asd2, and thrA. In summary, we acquired six novel regulators related to lincomycin biosynthesis, and elucidated the regulatory mechanism of AflQ1-Q2. This highly conserved TCS is a promising target for the construction of antibiotic high-yield strains. KEY POINTS: ⢠AflQ1-Q2 is a repressor for lincomycin production. ⢠AflQ1 modulates the expression of lincomycin biosynthetic and regulatory genes. ⢠Aspartate affects the behavior of AflQ2, and its metabolism is promoted by AflQ1.
Subject(s)
Aspartic Acid , Bacterial Proteins , Aspartic Acid/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Lincomycin , Anti-Bacterial Agents , Gene Expression Regulation, BacterialABSTRACT
Epigenetic modifications have received increasing attention and have been shown to be extensively involved in kidney development and disease progression. Among them, the most common RNA modification, N6 -methyladenosine (m6 A), has been shown to dynamically and reversibly exert its functions in multiple ways, including splicing, export, decay and translation initiation efficiency to regulate mRNA fate. Moreover, m6 A has also been reported to exert biological effects by destabilizing base pairing to modulate various functions of RNAs. Most importantly, an increasing number of kidney diseases, such as renal cell carcinoma, acute kidney injury and chronic kidney disease, have been found to be associated with aberrant m6 A patterns. In this review, we comprehensively review the critical roles of m6 A in kidney diseases and discuss the possibilities and relevance of m6 A-targeted epigenetic therapy, with an integrated comprehensive description of the detailed alterations in specific loci that contribute to cellular processes that are associated with kidney diseases.
Subject(s)
Acute Kidney Injury , Carcinoma, Renal Cell , Kidney Neoplasms , Humans , RNA , RNA, MessengerABSTRACT
Objective: To determine whether the visceral adiposity index (VAI) was linked to the risk of kidney stones (KS) in the representative U.S. adults. Methods: We investigated 59842 participants who joined the 2007-2018 National Health and Nutrition Examination Survey. The association between the visceral adiposity index (VAI) and KS was identified by logistic regression analysis. Meanwhile, the subgroup analysis as well as the calculation of dose-response curves were also utilized to identify sensitive groups. Results: Data from 29384 participants were available, including 2781 self-reported ever experiencing KS diseases. Overall, the VAI was 0.74 (0.70, 0.78) in the KS group, while 0.55 (0.52, 0.57) in the control group. After adjusting for confounders, the prevalence of KS increased by 13% for each unit of VAI increment (OR = 1.13, 95% CI: 1.08, 1.19). Moreover, a linear relationship was found between the VAI and the prevalence of KS. By subgroup analysis, we found that a positive correlation between VAI and the risk of KS both in male (OR=1.14, 95%CI:1.07, 1.22) and female (OR=1.14, 95%CI:1.05, 1.24), White (OR=1.20, 95%CI:1.11, 1.28) and other race, all aged subgroups, nonhypertensive (OR=1.06, 95%CI:1.08, 1.25) and nondiabetic subgroups (OR=1.14, 95%CI:1.07, 1.21). Conclusions: Elevated VAI was strongly associated with KS in representative U.S. adults, which may be a promising indicator for the risk of kidney stones.
Subject(s)
Adiposity , Kidney Calculi , Adult , Male , Female , Humans , Aged , Adiposity/physiology , Intra-Abdominal Fat , Nutrition Surveys , Obesity, Abdominal/complications , Obesity, Abdominal/epidemiology , Kidney Calculi/etiology , Kidney Calculi/complicationsABSTRACT
Calcium oxalate (CaOx) crystals, as the predominant component of human kidney stones, can trigger excessive cell death and inflammation of renal tubular epithelial cells, involved in the pathogenesis of nephrocalcinosis. Necroptosis mediated by receptor-interacting protein kinase 3 (RIPK3) serves a critical role in the cytotoxicity of CaOx crystals. Here, we assessed the therapeutic potential of a novel RIPK3 inhibitor, compound 42 (Cpd-42), for CaOx nephrocalcinosis by comparison with dabrafenib, a classic RIPK3 inhibitor. Our results demonstrated that Cpd-42 pretreatment attenuated CaOx crystals-induced renal tubular epithelial cell (TEC) injury by inhibiting necroptosis and inflammation in vitro and in vivo. Furthermore, in an established mouse model of CaOx nephrocalcinosis, Cpd-42 also reduced renal injury while improving the impaired kidney function and intrarenal crystal deposition. Consistent with this finding, Cpd-42 was confirmed to exhibit superior inhibition of necroptosis and protection against renal TEC injury compared to the classic RIPK3 inhibitor dabrafenib in vitro and in vivo. Mechanistically, RIPK3 knockout (KO) tubular epithelial cells pretreated with Cpd-42 did not show further enhancement of the protective effect on crystals-induced cell injury and inflammation. We confirmed that Cpd-42 exerted protective effects by specifically targeting and inhibiting RIPK3-mediated necroptosis to block the formation of the RIPK1-RIPK3 necrosome. Taken together, targeted inhibition of RIPK3-mediated necroptosis with Cpd-42 may provide a potential therapeutic approach for CaOx nephrocalcinosis.
ABSTRACT
BACKGROUND: Although hepatitis B virus (HBV) is a recognized risk factor for renal diseases, little is known about HBV infection in individuals with upper urinary calculi (UUC). We investigated the relationship between chronic HBV infection and UUC. METHODS: We retrospectively analysed data from 1399 patients who were discharged from the Department of Urology (2017-2018). The diagnosis of UUC was determined using urinary tract ultrasonography or computed tomography, and HBV infection was evaluated by a positive hepatitis B surface antigen (HBsAg) test. Data on patients with and without UUC and HBsAg-positive and HBsAg-negative patients were compared by univariate and multivariate analyses. RESULTS: Data on chronic HBV infection and UUC were available for 1062 patients, including 514 who presented with UUC and 548 who did not. Overall, 5.8% of total patients, 8.0% of UUC patients and 3.8% of non-UUC patients had chronic HBV infection. UUC patients (41/514) had a significantly higher prevalence of HBsAg positivity (OR 2.175; 95% CI 1.267-3.734; P = 0.004) than non-UUC patients (21/548). After stratifying by sex, the relative odds of HBsAg positivity were statistically significant in men (OR 2.156; 95% CI 1.162-4.003; P = 0.015) but not in women (OR 2.947; 95% CI 0.816-10.643; P = 0.099). The incidence of urinary pH > 6 and staghorn stones was significantly higher in HBsAg-positive UUC patients than in HBsAg-negative UUC patients. CONCLUSION: This is the first study to demonstrate that chronic HBV infection is strongly associated with UUC, at least in men. The urinary pH > 6 and staghorn stones were more common in UUC patients with chronic HBV infection.
Subject(s)
Hepatitis B, Chronic , Hepatitis B , Urinary Calculi , Urinary Tract , Female , Hepatitis B/complications , Hepatitis B/epidemiology , Hepatitis B Surface Antigens , Hepatitis B virus , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/epidemiology , Humans , Male , Retrospective Studies , Urinary Calculi/complications , Urinary Calculi/epidemiologyABSTRACT
AIMS: Assessing the role of ramRsl , a gene absent in a lincomycin over-producing strain, in the regulation of morphological development and lincomycin biosynthesis in Streptomyces lincolnensis. METHODS AND RESULTS: The gene ramRsl was deleted from the wild-type strain NRRL 2936 and the ΔramR mutant strain was characterized by a slower growth rate and a delayed morphological differentiation compared to the original strain NRRL 2936. Furthermore, the ΔramR produced 2.6-fold more lincomycin than the original strain, and consistently the level of expression of all lincomycin cluster located genes was enhanced at 48 and 96 h in the ΔramR. Complementation of ΔramR with an intact copy of ramRsl restored all wild-type features, whereas the over-expression of ramRsl led to a reduction of 33% of the lincomycin yield. Furthermore, the level of expression of glnR, bldA and SLCG_2919, three of known lincomycin biosynthesis regulators, was lower in the ΔramR than in the original strain at the early stage of fermentation and we demonstrated, using electrophoretic mobility shift assay and XylE reporter assay, that glnR is a novel direct target of RamR. CONCLUSIONS: Altogether, these results indicated that, beyond promoting the morphological development, RamR regulates negatively lincomycin biosynthesis and positively the expression of the nitrogen regulator GlnR. SIGNIFICANCE AND IMPACT OF THE STUDY: We demonstrated that RamR plays a negative role in the regulation of lincomycin biosynthesis in S. lincolnensis. Interestingly, the deletion of this gene in other antibiotic-producing Streptomyces strains might also increase their antibiotic-producing abilities.
Subject(s)
Gene Expression Regulation, Bacterial , Streptomyces , Anti-Bacterial Agents/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Lincomycin/metabolism , Streptomyces/genetics , Streptomyces/metabolismABSTRACT
PURPOSE: Severe haemorrhage in percutaneous nephrolithotomy (PCNL) is an alarming event, and preventing injury to renal major vessels is a challenge. We evaluated the efficiency of a blunt needle in renal puncture procedures. METHODS: We first retrospectively reviewed the embolization images of post-PCNL patients to analyse the types of arteries injured, which were considered target arteries. Then, either a blunt needle or a conventional needle was used to directly puncture target arteries in ex vivo porcine kidneys and to establish renal access ex vivo and in vivo. The primary outcome was the incidence of target artery injuries, which were observed by digital subtraction angiography, nephroscopy and 3-dimensional endocasts. The secondary outcome was the rate of excreted fluid per access. RESULTS: The segmental and interlobar arteries were the most common types of injured arteries that needed to be embolized after PCNL. When these arteries were punctured directly, blunt needles reduced injury (1/20 vs. 16/20; OR 4.750; 95% CI 1.966-11.478; P < .001) by 76% compared to injuries induced by conventional needles. Moreover, the blunt needle group also had a significantly lower incidence of these arteries' injuries ex vivo due to renal puncture and yielded a lower rate of excreted fluid in ex vivo and in vivo renal puncture procedures. CONCLUSION: A blunt needle for renal puncture can be effective in reducing injury to renal major arteries and the accompanying haemorrhage. We propose the concept of blunt puncture, which may be a promising method for achieving safe renal access in PCNL.
Subject(s)
Kidney Calculi , Nephrostomy, Percutaneous , Animals , Hemorrhage , Humans , Kidney/diagnostic imaging , Kidney/surgery , Kidney Calculi/surgery , Needles , Nephrostomy, Percutaneous/methods , Punctures , Retrospective Studies , SwineABSTRACT
Recently, an increasing number of investigators have debated the wide rule of the puncture to renal papilla in PCNL. We evaluated the effect of renal papillary and nonpapillary puncture on bleeding in an in vitro porcine kidney experience, with the aim of determining the safe puncture sites of collecting system in PCNL. A total of 70 fresh porcine kidneys were selected and subjected to nephrostomy. We performed a puncture through a renal papilla, infundibulum, renal column, or minor calyceal neck (including the front, back, up, and down). The primary outcome was the amount of bleeding. The results showed that the papillary puncture group yielded minimal bleeding (1.59 ± 1.01 ml/min) compared with the infundibular puncture group (6.25 ± 4.46 ml/min, P < .001), renal column puncture group (4.24 ± 3.79 ml/min, P = 0.001), and minor calyceal neck puncture group (2.27 ± 1.35 ml/min, P = 0.011). However, after stratifying by orientation, the up (1.75 ± 0.80 ml/min, P = 0.501) or down (1.77 ± 0.72 ml/min, P = 0.437) minor calyceal neck puncture group and papillary puncture group yielded comparable bleeding. In summary, nonpapillary puncture must be carefully considered. Infundibular and renal column punctures were inferior to papillary puncture, and up or down minor calyceal neck puncture may be a prudent choice in specific situations.
Subject(s)
Kidney Calculi , Nephrolithotomy, Percutaneous , Nephrostomy, Percutaneous , Animals , Female , Hemorrhage , Humans , Kidney/surgery , Kidney Calculi/surgery , Male , Nephrolithotomy, Percutaneous/adverse effects , Nephrolithotomy, Percutaneous/methods , Nephrostomy, Percutaneous/methods , Punctures/methods , Swine , Treatment OutcomeABSTRACT
Lincomycin is an important antimicrobial agent which is widely used in clinical and animal husbandry. The biosynthetic pathway of lincomycin comes to light in the past 10 years, however, the regulatory mechanism is still unclear. In this study, a redox-sensing regulator Rex from Streptomyces lincolnensis (Rexlin ) was identified and characterized to affect cell growth and lincomycin biosynthesis. Disruption of rex resulted in an increase in cell growth, but a decrease in lincomycin production. The results of quantitative real-time polymerase chain reaction showed that Rexlin can promote transcription of the regulatory gene lmbU and the structural genes lmbA, lmbC, lmbJ, lmbV, and lmbW. However, electrophoretic mobility shift assay analysis demonstrated that Rexlin can not bind to the promoter regions of these genes above. Findings in this study broadened our horizons in the regulatory mechanism of lincomycin production and laid a foundation for strain improvement of antibiotic producers.