A BCG kill switch strain protects against Mycobacterium tuberculosis in mice and non-human primates with improved safety and immunogenicity.

Improved vaccination strategies for tuberculosis are needed. Intravenous (i.v.

Engineered Mycobacterium tuberculosis triple-kill-switch strain provides controlled tuberculosis infection in animal models.

Human challenge experiments could accelerate tuberculosis vaccine development. This requires a safe Mycobacterium tuberculosis (Mtb) strain that can both replicate in the host and be reliably cleared. Here we genetically engineered Mtb strains encoding up to three kill switches: two mycobacteriophage lysin operons negatively regulated by tetracycline and a degron domain-NadE fusion, which induces ClpC1-dependent degradation of the essential enzyme NadE, negatively regulated by trimethoprim.

The Dual Role of Cellular Senescence in Macrophages: Unveiling the Hidden Driver of Age-Related Inflammation in Kidney Disease.

Aging is a complex biological process that involves the gradual decline of cellular, tissue, and organ functions. In kidney, aging manifests as tubular atrophy, glomerulosclerosis, and progressive renal function decline. The critical role of senescence-associated macrophage in diseases, particularly kidney diseases, is increasingly recognized.

Serum untargeted metabolomics analysis of uremic pruritus in patients with various etiologies.

Uremic pruritus (UP) is a prevalent complication of uremia, severely affecting the quality of life of patients. The abnormal and accumulation of metabolites in the circulatory system of UP patients may constitute a significant inducer of pruritus. However, a systematic evaluation of the differences in serum metabolomic profiles among UP patients with different etiologies has yet to be reported.

β-Adrenoceptor Signaling Activation Improves Bladder Fibrosis by Inhibiting Extracellular Matrix Deposition of Bladder Outlet Obstruction.

Background: Partial bladder outlet obstruction (pBOO) causes deposition of extracellular matrix (ECM), promotes bladder fibrosis, and decreases bladder compliance.

Methods: To investigate the effect of β-adrenoceptor (ADRB) on the ECM deposition of pBOO rat model and explore its underlying mechanism, human bladder smooth muscle cells (hBSMCs) were exposed to the pathological hydrostatic pressure (100 cm HO) for 6 h, reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were employed. Then the rats of sham operation and pBOO model were treated with vehicle or ADRB agonists for 3 weeks, and the alterations of the bladder were observed via Masson staining and immunohistochemical analysis.

Mechanism of Chaihuang-Yishen formula to attenuate renal fibrosis in the treatment of chronic kidney disease: Insights from network pharmacology and experimental validation.

Renal fibrosis represents a pivotal characteristic of chronic kidney disease (CKD), for which effective interventions are currently lacking. The Src kinase activates the phosphatidylinositol-3 kinases (PI3K)/Akt1 pathway to promote renal fibrosis, casting a promising target for anti-fibrosis treatment. Chaihuang-Yishen formula (CHYS), a traditional Chinese medicinal prescription, has a validated efficacy in the treatment of CKD, however, with the underlying mechanism unresolved.

Astragalus mongholicus bunge and panax notoginseng formula (A&P) improves renal fibrosis in UUO mice via inhibiting the long non-coding RNA A330074K22Rik and downregulating ferroptosis signaling.

Background: Chronic kidney disease (CKD) and its associated end-stage renal disease (ESRD) are significant health problems that pose a threat to human well-being. Renal fibrosis is a common feature and ultimate pathological outcome of various CKD leading to ESRD. The Astragalus mongholicus Bunge and Panax notoginseng formula (A&P) is a refined compound formulated by our research group, which has been clinically administered for over a decade and has demonstrated the ability to improve the inflammatory state of various acute or chronic kidney diseases.

Emodin suppresses mast cell migration via modulating the JAK2/STAT3/JMJD3/CXCR3 signaling to prevent cystitis.

Aims: This study aimed to determine the preventive effects of emodin on cyclophosphamide (CYP)-induced cystitis and to explore the molecular mechanism.

Methods: In vivo, mice were modeled by CYP. Before a half hour of CYP treatment, Jumonji domain-containing protein-3 (JMJD3) inhibitors (GSK-J4) and emodin were used to treat CYP model mice.

Screening of active components in and formula for anti-fibrosis in CKD: nobiletin inhibits Lgals1/PI3K/AKT signaling to improve renal fibrosis.

The and formula (A&P) has been clinically shown to effectively slow down the progression of chronic kidney disease (CKD) and has demonstrated significant anti-fibrosis effects in experimental CKD model. However, the specific active ingredients and underlying mechanism are still unclear. The active ingredients of A&P were analyzed by Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-HR-MS).

TGF‑β/Smad signaling in chronic kidney disease: Exploring post‑translational regulatory perspectives (Review).

The TGF‑β/Smad signaling pathway plays a pivotal role in the onset of glomerular and tubulointerstitial fibrosis in chronic kidney disease (CKD). The present review delves into the intricate post‑translational modulation of this pathway and its implications in CKD. Specifically, the impact of the TGF‑β/Smad pathway on various biological processes was investigated, encompassing not only renal tubular epithelial cell apoptosis, inflammation, myofibroblast activation and cellular aging, but also its role in autophagy.

Calycosin inhibited MIF-mediated inflammatory chemotaxis of macrophages to ameliorate ischemia reperfusion-induced acute kidney injury.

Background: Inflammatory macrophage infiltration plays a critical role in acute kidney disease induced by ischemia-reperfusion (IRI-AKI). Calycosin is a natural flavone with multiple bioactivities. This study aimed to investigate the therapeutic role of calycosin in IRI-AKI and its underlying mechanism.

Research on the global trends of COVID-19 associated acute kidney injury: a bibliometric analysis.

Critically ill COVID-19 patients may exhibit various clinical symptoms of renal dysfunction including severe Acute Kidney Injury (AKI). Currently, there is a lack of bibliometric analyses on COVID-19-related AKI. The aim of this study is to provide an overview of the current research status and hot topics regarding COVID-19 AKI.

Hederagenin improves renal fibrosis in diabetic nephropathy by regulating Smad3/NOX4/SLC7A11 signaling-mediated tubular cell ferroptosis.

Diabetic nephropathy (DN) is a common complication of diabetes, characterized by renal fibrosis and poor patient prognosis. Hederagenin (HDG) has shown promising improvement in chronic kidney disease (CKD) kidney fibrosis, but its mechanism in DN-induced kidney fibrosis remains unclear. In this study, a model of diabetic nephropathy (DN) in mice was induced by intraperitoneal injection of streptozocin (50 mg/kg), while in vitro, high glucose (25 mM) was used to induce HK2 cell damage, simulating tubular injury in DN kidneys.

Mincle as a potential intervention target for the prevention of inflammation and fibrosis (Review).

Macrophage‑inducible C‑type lectin receptor (Mincle) is predominantly found on antigen‑presenting cells. It can recognize specific ligands when stimulated by certain pathogens such as fungi and . This recognition triggers the activation of the nuclear factor‑κB pathway, leading to the production of inflammatory factors and contributing to the innate immune response of the host.

Data independent acquisition reveals in-depth serum proteome changes in uremic pruritus.

Uremic pruritus (UP) is a prevalent symptom in patients suffering from uremia, yet its underlying etiology and mechanisms remain incompletely elucidated. Given the significant incidence of UP, identifying specific alterations in proteins present in the blood of UP patients could offer insights into the potential biological pathways associated with UP and facilitate the exploration of biomarkers. In this study, we employed LC-MS/MS-based data-independent acquisition (DIA) mode to analyze serum samples obtained from 54 UP patients categorized as DKD-UP, HN-UP, and GN-UP (n = 18 for each subgroup), along with 18 uremic patients without pruritus (Negative) and 18 CKD patients without pruritus (CKD).

RfxCas13d-mediated inhibition of alleviates renal fibrosis via PI3K/AKT signaling pathway.

Background: Circular RNAs () have been shown to be involved in the development of chronic kidney disease (CKD). This study aimed to investigate the role of in renal fibrosis, which is a hallmark of CKD.

Methods: In this study, we established a unilateral ureteral obstruction (UUO) model and delivered RfxCas13d knockdown plasmid into renal parenchymal cells retrograde injection through the ureter followed by electroporation.

Kaempferitrin attenuates unilateral ureteral obstruction-induced renal inflammation and fibrosis in mice by inhibiting NOX4-mediated tubular ferroptosis.

Tubular ferroptosis significantly contributes to renal inflammation and fibrosis, critical factors in chronic kidney disease (CKD). This study aims to investigate Kaempferitrin, a potent flavonoid glycoside from Bauhinia forficata leaves, renowned for its anti-inflammatory and antitumor effects, and to elucidate its potential mechanisms in mitigating inflammation and fibrosis induced by tubular ferroptosis. The study investigated Kaempferitrin's impact on tubular ferroptosis using a unilateral ureteral obstruction (UUO) model-induced renal inflammation and fibrosis.

Emodin inhibits bladder inflammation and fibrosis in mice with interstitial cystitis by regulating JMJD3.

Purpose: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a devastating urological chronic pelvic pain condition. In search of a potential treatment, we investigated the effect of emodin on IC/BPS inflammation and fibrosis, and explore the potential mechanism.

Methods: An experimental model of interstitial cystitis was induced by cyclophosphamide, and human bladder smooth muscle cells were treated with lipopolysaccharide to establish the cell model in vitro.

Development of an Engineered Strain for a Safe and Effective Tuberculosis Human Challenge Model.

Human challenge experiments could greatly accelerate the development of a tuberculosis (TB) vaccine. Human challenge for tuberculosis requires a strain that can both replicate in the host and be reliably cleared. To accomplish this, we designed (Mtb) strains featuring up to three orthogonal kill switches, tightly regulated by exogenous tetracyclines and trimethoprim.

Btg2 Promotes Focal Segmental Glomerulosclerosis via Smad3-Dependent Podocyte-Mesenchymal Transition.

Podocyte injury plays a critical role in the progression of focal segmental glomerulosclerosis (FSGS). Here, it is reported that B-cell translocation gene 2 (Btg2) promotes Adriamycin (ADR)-induced FSGS via Smad3-dependent podocyte-mesenchymal transition. It is found that in FSGS patients and animal models, Btg2 is markedly upregulated by podocytes and correlated with progressive renal injury.

Modified Zhibai Dihuang pill alleviated urinary tract infection induced by extended-spectrum β-lactamase in rats by regulating biofilm formation.

Context: Zhibai Dihuang pill (ZD), a traditional Chinese medicine nourishes Yin and reduces internal heat, is believed to have therapeutic effects on urinary tract infections (UTIs).

Objective: To explore the effects and mechanism of modified ZD (MZD) on UTI induced by extended-spectrum β-lactamase (ESBLs) .

Materials And Methods: Thirty Sprague-Dawley rats were randomly divided into control, model (0.

Hederagenin ameliorates renal fibrosis in chronic kidney disease through blocking ISG15 regulated JAK/STAT signaling.

Interstitial fibrosis is the key pathological characteristics of chronic kidney diseases (CKD). In this study, we reported that hederagenin (HDG) can effectively improve the renal interstitial fibrosis and its mechanism. We constructed CKD animal models of ischemia reperfusion injury (IRI) and unilateral ureteral obstruction (UUO) respectively to observe the improvement effect of HDG on CKD.