Curcumin has been shown to inhibit renal fibrosis, but whether curcumin mediates renal fibrosis progression by regulating the circular RNA (circRNA)-related pathway remain unclear.

TGF-β1 was used to construct renal injury and fibrosis cell model. Cell growth was evaluated by cell counting kit 8 assay, EdU assay and flow cytometry. Fibrosis marker and interleukin 6 signal transducer (IL6ST) protein levels were measured using western bolt analysis. Inflammation factor concentrations were determined by ELISA. Circ_0008925, miR-204-5p and IL6ST expression was assessed by qRT-PCR. Unilateral ureteral obstruction (UUO) mice models were constructed to assess the role of curcumin in vivo.

Curcumin treatment alleviated TGF-β1-induced HK-2 cell apoptosis, inflammation and fibrosis in vitro, as well as relieved renal injury in UUO mice models in vivo. Circ_0008925 was highly expressed in TGF-β1-induced HK-2 cells and its expression was inhibited by curcumin. Circ_0008925 could sponge miR-204-5p to positively regulate IL6ST. The inhibition effect of curcumin on TGF-β1-induced HK-2 cell injury and fibrosis was reversed by circ_0008925 overexpression, miR-204-5p inhibitor or IL6ST upregulation. Besides, circ_0008925 knockdown inhibited TGF-β1-induced HK-2 cell injury and fibrosis by suppressing IL6ST expression.

Curcumin relieved renal fibrosis through regulating circ_0008925/miR-204-5p/IL6ST axis.

The clinical application of cyclosporine A (CsA) is limited due to nephrotoxicity. Lipid metabolism disorders play important roles in renal injury, but their role in CsA nephrotoxicity is not yet clear. Huangqi (Astragalus mongholicus Bunge) and Danshen (Salvia miltiorrhiza Bunge) (HD) play roles in ameliorating the nephrotoxicity of CsA, but their mechanisms still need to be fully clarified.

This study innovatively aimed to analyse the coexpression of renal proteins and serum metabolites for the identification of key pathways and targets. This study provides novel insight into the mechanism by which HD ameliorates CsA-induced nephrotoxicity.

We utilized HD to intervene in both in vivo and in vitro nephrotoxicity models induced by CsA. For the in vivo experiments, we constructed a coexpression network of renal proteins and serum metabolites, which was used to screen for key pathways. To validate these findings, we knocked down key proteins in vivo. For the in vitro studies, we employed MTT, Transwell, flow cytometry, and immunofluorescence assays to monitor the epithelial-mesenchymal transition (EMT) of HK-2 cells. Additionally, we used electron microscopy and Seahorse assays to examine the effects of HD on mitochondrial structure and function. Furthermore, we overexpressed Ppara to further confirm the mechanism by which HD improves renal function.

HD can improve renal pathological damage and function; regulate blood lipids, inflammation and oxidative stress indicators; and reduce apoptosis in renal tissues. Joint protein and metabolomics analyses revealed that two lipid metabolism-related pathways (the PPAR signalling pathway and linoleic acid metabolism pathway) were coenriched, involving six differential proteins (Cyp2e1, Cyp4a10, Gk, Lpl, Ppara, and Pck1) and two differentially abundant metabolites (alpha-Dimorphecolic acid and 12,13-EpOME). Western blot was used to verify differentially expressed proteins. HD improved mitochondrial damage and lipid accumulation, as demonstrated by transmission electron microscopy (TEM) analysis and Oil Red O staining. Knockdown of the key protein Ppara affected the expression of ACOX1 and exacerbated RF. In vitro verification demonstrated that HD significantly inhibited CsA-induced EMT in HK-2 cells and improved mitochondrial structure and function. Ppara overexpression promoted HD-mediated regulation of mitochondrial function, reduced apoptosis, and improved HK-2 RF.

HD can ameliorate CsA nephrotoxicity through renal protein-serum metabolism coexpression, the PPAR signalling pathway, and linoleic acid metabolism. HD-induced upregulation of Ppara to regulate lipid metabolism, improve mitochondrial function and reduce apoptosis are important mechanisms. The Ppara/ACOX1/TGF-β1 axis may play an important role in this process. These findings offer potential targets for the future development of therapeutic strategies and novel drugs.

Chronic kidney disease (CKD) has become a significant global public health challenge, which was reported to be highly correlated with the triglyceride glucose-body mass index (TyG-BMI). Nevertheless, literature exploring the association between changes in the TyG-BMI and CKD incidence is scant, with most studies focusing on individual values of the TyG-BMI. We aimed to investigate whether cumulative average in the TyG-BMI were associated with CKD incidence.

Data in our study were obtained from the China Health and Retirement Longitudinal Study (CHARLS), which is an ongoing nationally representative prospective cohort study. The exposure was the cumulative average TyG-BMI from 2011 to 2015. The TyG-BMI was calculated by the formula ln [TG (mg/dl) × FBG (mg/dl)/2] × BMI (kg/m2), and the cumulative average TyG-BMI was calculated as follows: (TyG-BMI2011+ TyG-BMI2015)/2. Logistic regressions were used to determine the association between different quartiles of cumulative average TyG-BMI and CKD incidence. Meanwhile, restricted cubic spline was applied to examine the potential nonlinear association of the cumulative average TyG-BMI and CKD incidence. In addition, subgroup analysis was used to test the robustness of results.

Of the 6117 participants (mean [SD] age at baseline, 58.64 [8.61] years), 2793 (45.7%) were men. During the 4 years of follow-up, 470 (7.7%) incident CKD cases were identified. After adjusting for potential confounders, compared to the participants in the lowest quartile of cumulative average TyG-BMI, participants in the 3rd and 4th quartile had a higher risk of CKD onset. The ORs and 95%CIs were [1.509(1.147, 1.990)] and [1.452(1.085, 1.948)] respectively. In addition, restricted cubic spline showed the cumulative average TyG-BMI had a liner association (p-nonlinear = 0.139).

The cumulative average in the TyG-BMI was independently associated with the risk of CKD in middle-aged and older adults. Monitoring long-term changes in the TyG-BMI may assist with the early identification of individuals at high risk of CKD.

The level of urinary albumin is a critical indicator for the early diagnosis and management of chronic kidney disease (CKD). However, existing methods for detecting albumin are not conducive to point-of-care testing due to the complexity of reagent addition and incubation processes. This study presents a smartphone-integrated handheld automated biochemical analyzer (sHABA) designed for point-of-care testing of urinary albumin. The sHABA features a pre-loaded, disposable reagent cassette with reagents for the albumin assay arranged in the order of their addition within a hose. The smartphone-integrated analyzer can drive the reagents following a preset program, to enable automatic sequential addition. The sHABA has a detection limit for albumin of 5.9 mg/L and a linear detection range from 7 to 450 mg/L. The consistency of albumin level detection in 931 urine samples using sHABA with clinical tests indicates good sensitivity (95.78%) and specificity (90.16%). This research advances the field by providing an automated detection method for albumin in a portable device, allowing even untrained individuals to monitor CKD in real time at the patient's bedside. In the context of promoting tiered diagnosis and treatment, the sHABA has the potential to become an essential tool for the early diagnosis and comprehensive management of CKD and other chronic conditions.

Protein-energy wasting (PEW) facilitates major adverse clinical outcomes in chronic renal failure (CRF), with current therapies not suitable for all patients. Faecalibacterium prausnitzii (F. prausnitzii) can alleviate chronic kidney disease, with unclear effects and mechanisms on CRF with PEW. The CRF rat model was constructed by adenine administration, and PEW was induced by a 4% casein diet. The serum creatinine (SCR), urinary protein (UPR), and blood urea nitrogen (BUN) levels were measured by enzyme-linked immunosorbent assay. Pathology of the gastrocnemius muscle was estimated using hematoxylin and eosin staining. The expression of mitophagy-related markers was detected to assess the mitophagy level. Dexamethasone-induced L6 myotubes established myotube atrophy models. The levels of mitophagy-related markers, muscle RING-finger protein-1 (MuRF1), and atrophy gene 1 (Atrogin1) were detected by quantitative reverse transcription-polymerase chain reaction and western blotting. F. prausnitzii suppressed the SCR, UPR, and BUN expression in serum and gastrocnemius muscle atrophy, which were promoted by CRF with PEW. Dexamethasone-induced expression of MuRF1 and Atrogin1 in L6 myotubes was decreased by F. prausnitzii. Additionally, F. prausnitzii repressed mitophagy in the gastrocnemius muscle and L6 myotubes. In conclusion, F. prausnitzii suppressed renal failure progression and muscle atrophy by inhibiting mitophagy in CRF with PEW.

Exposure to environmental cadmium can have harmful effects on the human kidneys. The relationship between the degree of exposure to cadmium and the risk of chronic kidney disease (CKD) in the general population is unclear.

To investigate the association between blood cadmium levels and CKD risk using samples from the Korea National Health and Nutrition Examination Survey (KNHANES) VII data, which included heavy metal and serum creatinine levels.

We analyzed the data of 4,222 adults from January 1, 2016, to December 31, 2017. Multiple logistic regression analysis was conducted on weighted data using complex sampling to assess the relationship between blood cadmium levels and CKD. We performed a stratified analysis in the presence of comorbidities such as diabetes or hypertension.

There was a positive association between blood cadmium level and the risk of CKD in hypertensive or nondiabetic participants after adjustment, but not between blood cadmium level and CKD in normotensive or diabetic participants. The corresponding odds ratios (OR) of cadmium for CKD were 2.70 (95% confidence interval [CI], 1.49-4.90, P = 0.001) in samples with hypertension and 2.40 (95% CI, 1.56-3.70, P < 0.001) in samples without diabetes.

Our findings suggest an association between blood cadmium level and the risk of CKD in hypertensive or nondiabetic participants. Additional research is necessary to elucidate the relationship between cadmium exposure and CKD risk, particularly in individuals with comorbidities.

This study aimed to investigate the relationship between the triglyceride-glucose (TyG) index, its combination with the body roundness index (BRI), and chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM) based on a cross-sectional analysis conducted in Eastern China.

The research originates from a cross-sectional study performed in Zhejiang Province, Eastern China, between March and November 2018. The TyG-BRI index was calculated based on triglyceride, fasting blood glucose, and the BRI. The correlation between the TyG-BRI index and the risk of CKD was assessed using a restricted cubic spline model. A multivariate logistic regression model was used to investigate the association between the TyG-BRI index and the risk of CKD. Receiver operating characteristic (ROC) analyses was used to evaluate the optimal cut-off and value of the TyG-BRI index for predicting CKD.

A total of 1756 T2DM participants were enrolled in this study. The TyG-BRI index was significantly higher in participants with CKD than in those without CKD. In the fully adjusted model, the odds ratios for CKD in the second, third, and fourth TyG-BRI quartiles were 0.93 (95% CI: 0.65-1.33), 1.33 (95% CI: 0.94-1.88), and 1.57 (95% CI: 1.10-2.25), respectively, compared to the first quartile. RCS analysis confirmed a linear dose-response relationship between the TyG-BRI index and CKD risk (all p for nonlinearity > 0.05). ROC curve analysis revealed that the TyG-BRI index had moderate predictive value for CKD, with an area under the curve of 0.626 (95% CI: 0.597-0.656, p < 0.001). The optimal cut-off value for the TyG-BRI index was 42.46, with a sensitivity of 68.2% and specificity of 52.2%.

The TyG-BRI index was positively associated with the risk of CKD in a T2DM population, demonstrating a dose-response relationship and moderate predictive value. It may serve as a valuable tool for identifying high-risk individuals and informing targeted interventions to prevent or delay CKD progression in this population.

Chronic nephrotoxicity caused by CNIs (CICN) manifests clinically as chronic kidney disease (CKD). Astragaloside IV (AS-IV) plays a certain role in the treatment of CKD. This study aimed to verify the ameliorative effects of AS-IV on CICN and further explore the mechanisms underlying the modulation of the "gut-transcriptome-metabolome coexpression network" by AS-IV within the context of the "gut-kidney axis" to improve CICN.

Five groups of 40 mice were studied: a normal group (N, olive oil), a model group (M, CsA, 30 mg kg--1 d-1), a low-dose AS-IV group (CsA + AS-IV, 30 mg kg-1 d-1 + 10 mg kg-1 d-1), a high-dose AS-IV group (CsA + AS-IV, 30 mg kg-1 d-1 + 20 mg kg-1 d-1), and a valsartan group (CsA + Val, 30 mg kg-1 d-1 + 10 mg kg-1 d-1). The gut microbiota, renal transcriptome, and urine metabolome were separately detected to construct a gut-transcriptome-metabolome coexpression network. The target species, target genes, and target metabolites of AS-IV were evaluated.

CsA led to increased proteinuria and a deterioration of kidney function, accompanied by increased inflammation and oxidative stress, whereas AS-IV improved kidney damage. AS-IV inhibited intestinal permeability and disrupted the microbiota structure, increasing the abundance of Lactobacillus reuteri, Bifidobacterium animalis, Ignatzschineria indica, and Blautia glucerasea. Six coexpression pathways related to transcription and metabolism, including the citrate cycle, ascorbate and aldarate metabolism, proximal tubule bicarbonate reclamation, glycolysis/gluconeogenesis, ferroptosis, and drug metabolism-cytochrome P450, were identified. Seven target metabolites of AS-IV were identified in the 6 pathways, including UDP-D-galacturonic acid, 2-phenylethanol glucuronide, dehydroascorbic acid, isopentenyl pyrophosphate, alpha-D-glucose, 3-carboxy-1-hydroxypropylthiamine diphosphate and citalopram aldehyde. Five target genes of AS-IV, Ugt1a2, Ugt1a9, Ugt1a5, Pck1, and Slc7a11, were also identified and predicted by NONMMUT144584.1, MSTRG.30357.1 and ENSMUST00000174821. Lactobacillus reuteri was highly correlated with renal function and the target genes and metabolites of AS-IV. The target genes and metabolites of AS-IV were further validated. AS-IV inhibited intestinal-derived urinary toxins and improved renal tissue apoptosis, lipid accumulation, collagen deposition, and mitochondrial damage.

AS-IV improved CICN through the coexpression of the gut-transcriptome-metabolome network. The six pathways related to energy metabolism driven by L. reuteri, including the citrate cycle, ascorbate and alderate metabolism, proximal tube bicarbonate metabolism, glycolysis/gluconeogenesis, ferroptosis, drug metabolism-cytochrome P450, are important mechanisms.

Obesity has emerged as a global epidemic with far-reaching health complications, including its role as an independent risk factor for chronic kidney disease (CKD). Increasing evidence suggests that obesity contributes to CKD through multiple mechanisms, including chronic inflammation, hemodynamic alterations, insulin resistance, and lipid accumulation. These processes can culminate in histopathological changes collectively referred to as obesity-related glomerulopathy (ORG). This review aims to provide a comprehensive overview of the current knowledge regarding the prevalence, clinical manifestations, and pathophysiology of ORG. Furthermore, we emphasize the importance of identifying key biomarkers that facilitate the early detection of ORG. Finally, we explore emerging therapeutic strategies that offer promise in mitigating this growing global health crisis.

Tacrolimus (TAC)-induced chronic nephrotoxicity (TAC nephrotoxicity) is a serious issue for long-term graft survival in kidney transplantation. However, the pathophysiology of TAC nephrotoxicity remains unclear. In this study, we analyzed whole blood samples from mice that developed TAC nephrotoxicity in order to discover its mechanism. Mice were divided into a TAC group and a control group (n = 5 per group). The TAC group received TAC subcutaneously (1 mg/kg/day for 28 days), while the control group received normal saline instead. After the administration period, whole blood was collected and metabolomic analysis was performed, revealing significant changes in 56 metabolites. The major metabolic changes were related to uremic toxins, vascular damage, and NAD+. NAD+ levels were significantly lower in the TAC group, and ADP-ribose, nicotinamide, and nicotinamide N-oxide, which are degradation products of NAD+, were significantly higher, suggesting impairment of the NAD+ salvage pathway. NAD+ deficiency suggests cellular aging and mitochondrial dysfunction, which may induce vascular damage and chronic kidney disease. Our study demonstrated a correlation between low NAD+ levels and the pathophysiology of TAC nephrotoxicity.

Chiral metabolomics entails the enantioselective measurement of the metabolome present in a biological system. Over recent years, it has garnered significant interest for its potential in discovering disease biomarkers and aiding clinical diagnostics. D-Amino acids and D-hydroxy acids, traditionally overlooked as unnatural, are now emerging as novel signaling molecules and potential biomarkers for a range of metabolic disorders, brain diseases, kidney disease, diabetes, and cancer. Despite their significance, simultaneous measurements of multiple classes of chiral metabolites in a biological system remain challenging. Hence, limited information is available regarding the metabolic pathways responsible for synthesizing D-amino/hydroxy acid and their associated pathophysiological mechanisms in various diseases. Capitalizing on recent advancements in sensitive analytical techniques, researchers have developed various targeted chiral metabolomic methods for the analysis of chiral biomarkers. Here, we highlight the pivotal role of chiral metabolic profiling studies in disease diagnosis, prognosis, and therapeutic interventions. Furthermore, we describe cutting-edge chromatographic and mass spectrometry methods that enable enantioselective analysis of chiral metabolites. These advanced techniques are instrumental in unraveling the complexities of disease biomarkers, contributing to the ongoing efforts in disease biomarker discovery.

This research investigated the effects of different hemodialysis modalities combined with low-calcium dialysate (LCD) on mineral metabolism and vascular calcification (VC) in maintenance hemodialysis (MHD) patients with chronic kidney disease (CKD).

General data were collected from 192 cases of MHD patients, who were divided into 4 groups according to the randomized numerical table. Each group was given LCD treatment, and conventional hemodialysis (HD), high-flux HD (HFHD), hemodiafiltration (HDF), and HD + hemoperfusion (HP) were performed, respectively. The patients were dialyzed 3 times per week for 4 h each time, and each group was treated for 6 months. Fasting venous blood was collected. Serum interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high-sensitive C-reactive protein (hs-CRP) levels were measured by ELISA, calcium (Ca2+), phosphorus (P), Ca2+-P product, serum creatinine (SCr), blood urea nitrogen (BUN), β2 microglobulin (β2-MG), and intact parathyroid hormone (iPTH) were measured by chemiluminescence immunoassay, serum alkaline phosphatase (ALP) was determined by turbidimetric assay, and 25-hydroxyvitamin D (25(OH)D) was measured by autoradiographic immunoassay. To assess the extent of calcification in the iliac artery and abdominal aorta, a multilayer spiral CT device was employed for abdominal scans.

Serum IL-6, hs-CRP, TNF-α, Ca2+, P, Ca2+-P product, SCr, BUN, β2-MG, iPTH, and ALP levels decreased, while 25(OH)D levels increased in the four groups after treatment. The most pronounced effect on the reduction of IL-6, hs-CRP, TNF-α, Ca2+, P, Ca2+-P product, SCr, BUN, β2-MG, iPTH, and ALP was in the HD + HP group, followed by the HDF and HFHD groups, and then by the HD group. The rate of VC in the HDF, HFHD, and HD + HP groups was lower than that in the HD group, and the rate in the HD + HP group was lower than that in the HDF and HFHD groups.

The combination of HD + HP and LCD in treating CKD with MHD is effective, evidently rectifying disruptions in serum Ca2+ and P metabolism, enhancing kidney function, lessening the body's inflammatory response, and lessening VC.

Qi Teng Xiao Zhuo granule (QTXZG), a compound preparation used in traditional Chinese medicine, is a highly effective treatment for chronic glomerulonephritis (CGN). Previously, the mechanism of circStk4 and the N6-methyladenosine (m6A) modification of circStk4 in CGN was elucidated in vivo. Nevertheless, there hasn't been any research done on the connection between circStk4 and QTXZG's mechanism in CGN treatment.

The current study intended to clarify the molecular mechanism of QTXZG in CGN therapy by both in vitro and in vivo investigations.

Mouse mesangial cells (MMCs) were used to measure the rate of proliferation and apoptosis using flow cytometry and the Cell Counting Kit-8 (CCK-8) assay. The expression of markers associated with proliferation, apoptosis, and autophagy was analysed using reverse transcription quantitative PCR (RT-qPCR), western blotting (WB), and immunofluorescence (IF), respectively. Methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR) was utilized to analyse the m6A modification of circStk4, and METTL3 expression was assessed using RT-qPCR. Subsequently, miR-133a-3p and C1 expression was examined using RT-qPCR, WB, and IF. Adeno-associated virus 9 (AAV9)-circStk4 knockdown vector and a METTL3 inhibitor were used to explore the roles of METTL3 and circStk4 in CGN. Additionally, molecular docking and cellular thermal shift assays (CETSAs) were performed to assess the binding affinity between METTL3 and the active compounds in QTXZG.

Mechanistically, QTXZG reduced METTL3 expression and decreased circStk4 m6A levels while decreasing circStk4 levels and regulating the miR-133a-3p/C1 axis. Functionally, QTXZG inhibited MMCs and renal tissue proliferation, promoted apoptosis and autophagy, and reduced inflammation. In vivo experiments further confirmed that downregulated ircStk4 and METTL3 expression were accompanied by the therapeutic effects of QTXZG, resulting in a significant attenuation of renal injury, reduction in inflammation, inhibition of renal tissue proliferation and promotion of apoptosis and autophagy.

The present study revealed that QTXZG reduced circStk4 m6A and METTL3 expression to regulate the circStk4/miR-133a-3p/C1 axis in the treatment of CGN and thus inhibited glomerular tissue/membrane cell proliferation and promoted autophagy and apoptosis; these results uncovered a new mechanism by which QTXZG reduced CGN and imply that METTL3 might be a target for innovative therapeutic approaches.

This study aimed to identify biomarkers for chronic kidney disease (CKD) by studying serum metabolomics. Serum samples were collected from 194 non-dialysis CKD patients and 317 healthy controls (HC). Using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS), untargeted metabolomics analysis was conducted. A random forest model was developed and validated in separate sets of HC and CKD patients. The serum metabolomic profiles of patients with chronic kidney disease (CKD) exhibited significant differences compared to healthy controls (HC). A total of 314 metabolites were identified as significantly different, with 179 being upregulated and 135 being downregulated in CKD patients. KEGG enrichment analysis revealed several key pathways, including arginine biosynthesis, phenylalanine metabolism, linoleic acid metabolism, and purine metabolism. The diagnostic efficacy of the classifier was high, with an area under the curve of 1 in the training and validation sets and 0.9435 in the cross-validation set. This study provides comprehensive insights into serum metabolism in non-dialysis CKD patients, highlighting the potential involvement of abnormal biological metabolism in CKD pathogenesis. Exploring metabolites may offer new possibilities for the management of CKD.

JNK-associated leucine zipper protein (JLP) is a newly identified renal endogenous anti-fibrotic factor that is selectively enriched in renal tubular epithelial cells (TECs). The loss of JLP by TECs is a landmark event that heralds the progression of kidney fibrosis. JLP deficiency ensues a series of pathogenetic cellular processes that are conducive to fibrotic injury. Inflammatory injury is functionally relevant in fibrotic kidneys, and TECs play an essential role in fueling inflammation through aberrant secretions. It is speculated that the loss of JLP in TECs is associated with the relentless inflammation during the development of kidney fibrosis. This study examined the alteration of a panel of inflammatory signatures in TECs under kidney fibrotic circumstances using a Jlp gene-modified unilateral ureteral obstruction (UUO) mouse model or cultured HK-2 cells. It was found that a deficiency of JLP in TECs led to a significant increase in the secretion of inflammatory cytokines including interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), and monocyte chemotactic protein-1 (MCP-1), overactivation of the nuclear factor (NF)-κB/c-Jun N-terminal kinase (JNK) pathway, as well as nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis in response to pro-fibrotic damage. Additionally, the absence of JLP resulted in enhanced macrophage migration and fibroblast activation as paracrine effects elicited by injured TECs. In conclusion, the loss of JLP in TECs catalyses inflammatory injuries in the development of kidney fibrosis.

Renal fibrosis is a process in which excessive deposition of extracellular matrix leads to an increase in tissue hardness and gradual destruction of the renal parenchyma. Chronic kidney disease (CKD) commonly progresses to end-stage renal disease (ESRD), ultimately leading to renal failure. This disease has high incidence and mortality rates, but to date, effective treatment options are lacking. PEP-Z-2 is a collagen peptide isolated from redlip croaker scales and may have potential fibroprotective activity. In this study, PEP-Z-2 was found to alleviate unilateral ureteral obstruction (UUO)- and folic acid (FA)-induced kidney injury in a mouse model, reduce collagen deposition in tissues, normalize renal function, reduce the expression of fibrosis markers, reduce reactive oxygen species (ROS) production, and restore the balance of the oxidant/antioxidant system. In vitro experiments also demonstrated that PEP-Z-2 inhibits the TGF-β-induced differentiation of fibroblasts and renal tubular epithelial cells into myofibroblasts and reduces the production of extracellular matrix (ECM) proteins such as fibronectin, Col I, and α-SMA, demonstrating notable therapeutic effects on renal fibrosis. This effect is achieved by regulating the TGF-β/Smad/AKT/MAPK pathway. Our research suggested that PEP-Z-2 is a potential therapeutic drug for renal fibrosis, and peptides from aquatic organisms may constitute a new class of candidate drugs for the treatment of renal fibrosis and even other types of organ fibrosis.

Chronic Kidney Disease (CKD), is often detected late due to its asymptomatic nature in the early stage of the disease. Overproduction of reactive oxygen species contributes to various pathological processes through oxidative stress (OS), impacting on cellular structures and functions with previous studies suggesting a link between OS and CKD progression. This study investigated the association between serum peroxiredoxin-4 (Prx4), a biomarker of oxidative stress, and the development of CKD in the general population.

This study featured data from the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort, involving 5341 participants without CKD at baseline who underwent extensive prospective health evaluations. Serum Prx4 levels were quantified using an immunoluminometric assay. The primary outcome was new-onset CKD as defined by the composite of urinary albumin excretion (UAE) > 30 mg/24-h, an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, or both.

Baseline median Prx4 level was 0.65 [interquartile range (IQR): 0.42-1.04] U/L, median eGFR was 98 [IQR: 87-108] mL/min/1.73 m2, and median UAE was 8.1 [IQR: 6.0-12.1] mg/L. During a median follow-up of 10.4 [IQR: 6.3-11.4] years, 867 (16.2 %) patients developed new-onset CKD. Higher Prx4 levels were significantly associated with an increased risk of CKD (hazard ratio (HR) per doubling: 1.29 [95 % confidence interval (CI): 1.21-1.37], p < 0.001), also after adjustment for risk factors including sex, smoking status, systolic blood pressure, high-sensitive C-reactive protein, chronic heart failure, diabetes mellitus and dyslipidemia (HR per doubling: 1.16 [1.06-1.24], p < 0.001). Sensitivity analyses confirmed the robustness of these findings.

This study supports the hypothesis that systemic oxidative stress, reflected by higher serum Prx4 levels, is significantly associated with the risk of developing CKD in the general population. These findings suggest that Prx4 could be a valuable biomarker for early risk stratification and prevention strategies in CKD management.

Primary glomerular disease (PGD) is an idiopathic cause of renal glomerular lesions that is characterized by proteinuria or hematuria and is the leading cause of chronic kidney disease (CKD). The identification of circulating biomarkers for the diagnosis of PGD requires a thorough understanding of the metabolic defects involved. In this study, ultra-high performance liquid chromatography-tandem mass spectrometry was performed to characterize the amino acid (AA) profiles of patients with pathologically diagnosed PGD, including minimal change disease (MCD), focal segmental glomerular sclerosis (FSGS), membranous nephropathy, and immunoglobulin A nephropathy. The plasma concentrations of asparagine and ornithine were low, and that of aspartic acid was high, in patients with all the pathologic types of PGD, compared to healthy controls. Two distinct diagnostic models were generated using the differential plasma AA profiles using logistic regression and receiver operating characteristic analyses, with areas under the curves of 1.000 and accuracies up to 100.0% in patients with MCD and FSGS. In conclusion, the progression of PGD is associated with alterations in AA profiles, The present findings provide a theoretical basis for the use of AAs as a non-invasive, real-time, rapid, and simple biomarker for the diagnosis of various pathologic types of PGD.

Chronic kidney disease (CKD) is becoming increasingly prevalent worldwide, particularly among the elderly, along with an increase in the incidence of hypertension and cardiovascular disorders. Developing lipid-based oral dosage forms with a higher expected bioavailability of antihypertensive drugs with nephroprotective effects poses a challenge. Lercanidipine hydrochloride (LRCH) is a newer type of third-generation dihydropyridine calcium channel blocker that functions as an antihypertensive and has significant nephroprotective effects. Due to its extensive first-pass metabolism, its bioavailability is about 10% and increases to 3-4 times when taken with a high-fat meal. Targeting this drug to the lymphatic system using the solid self-nano-emulsifying drug delivery system (SSNEDDS) is a promising approach for improving LRCH's bioavailability and dispersion rate. SSNEDDS combines the benefits of both liquid self-emulsifying and solid dosage forms, improving drug stability and extending storage time.

In this study, liquid SNEDDS composed of 10% peppermint oil, 67% Tween 20, and 22.5% propylene glycol was solidified using two adsorbent agent mixtures (SSNEDDS1: Avicel PH 101 and Aerosil 200) and (SSNEDDS2: Avicel PH 102 and Aerosil 200) separately. The prepared formulations were evaluated for powder flow, drug content, and an in-vitro dispersion test in comparison to the brand-marketed tablet as a standard or pure drug. DSC and X-ray diffraction analysis were also used.

The SSNEDDS2 shows excellent flowability, a higher drug content (99.761%), and a significantly higher and faster dispersion rate of 100% within 10 minutes compared to 92% of the marketed LRCH tablet and 18.1% of the pure drug for 60 minutes. The solid-state characterization of the formulation composed of SSNEDDS2 confirmed that the LRCH was in an amorphous form inside the solidified nano system without interacting with the excipient.

This study successfully prepared LRCH using the promising strategy of SSNEDDS as a hard gelatin capsule with a higher dispersion rate. It improved its stability and expected bioavailability compared to the brand-marketed tablet as the standard.

Various medical conditions and the drugs used to treat them have been shown to impede or complicate dental implant surgery. It is crucial to carefully monitor the medical status and potential post-operative complications of patients with systemic diseases, particularly elderly patients, to minimize the risk of health complications that may arise.

The purpose of this study was to review the existing evidence on the viability of dental implants in patients with systemic diseases and to provide practical recommendations to achieve the best possible results in the corresponding patient population.

The information for our study was compiled using data from PubMed, Scopus, Web of Science and Google Scholar databases and searched separately for each systemic disease included in our work until October 2023. An additional manual search was also performed to increase the search sensitivity. Only English-language publications were included and assessed according to titles, abstracts and full texts.

In total, 6784 studies were found. After checking for duplicates and full-text availability, screening for the inclusion criteria and manually searching reference lists, 570 articles remained to be considered in this study.

In treating patients with systemic conditions, the cost-benefit analysis should consider the patient's quality of life and expected lifespan. The success of dental implants depends heavily on ensuring appropriate maintenance therapy, ideal oral hygiene standards, no smoking and avoiding other risk factors. Indications and contraindications for dental implants in cases of systemic diseases are yet to be more understood; broader and hardcore research needs to be done for a guideline foundation.

Chirality, the property of molecules having mirror-image forms, plays a crucial role in pharmaceutical and biomedical research. This review highlights its growing importance, emphasizing how chiral drugs and nanomaterials impact drug effectiveness, safety, and diagnostics. Chiral molecules serve as precise diagnostic tools, aiding in accurate disease detection through unique biomolecule interactions. The article extensively covers chiral drug applications in treating cardiovascular diseases, CNS disorders, local anesthesia, anti-inflammatories, antimicrobials, and anticancer drugs. Additionally, it explores the emerging field of chiral nanomaterials, highlighting their suitability for biomedical applications in diagnostics and therapeutics, enhancing medical treatments.

Metabolomics is an emerging and powerful technology that offers a comprehensive view of an organism's physiological status. Although widely applied in human medicine, it is only recently making its introduction in veterinary medicine. As a result, validated metabolomics protocols in feline medicine are lacking at the moment. Since biological interpretation of metabolomics data can be misled by the extraction method used, species and matrix-specific optimized and validated metabolomic protocols are sorely needed.

Systematic optimization was performed using fractional factorial experiments for both serum (n = 57) and urine (n = 24), evaluating dilution for both matrices, and aliquot and solvent volume, protein precipitation time and temperature for serum. For the targeted (n = 76) and untargeted (n = 1949) validation of serum respectively, excellent instrumental, intra-assay and inter-day precision were observed (CV ≤ 15% or 30%, respectively). Linearity deemed sufficient both targeted and untargeted (R2 ≥ 0.99 or 0.90, respectively). An appropriate targeted recovery between 70 and 130% was achieved. For the targeted (n = 69) and untargeted (n = 2348) validation of the urinary protocol, excellent instrumental and intra-assay precision were obtained (CV ≤ 15% or 30%, respectively). Subsequently, the discriminative ability of our metabolomics methods was confirmed for feline chronic kidney disease (CKD) by univariate statistics (n = 41 significant metabolites for serum, and n = 55 for urine, p-value<0.05) and validated OPLS-DA models (R2(Y) > 0.95, Q2(Y) > 0.65, p-value<0.001 for both matrices).

This study is the first to present an optimized and validated wholistic metabolomics methods for feline serum and urine using ultra-high performance liquid chromatography coupled to quadrupole-Orbitrap high-resolution mass spectrometry. This robust methodology opens avenues for biomarker panel selection and a deeper understanding of feline CKD pathophysiology and other feline applications.

Ovarian cancer (OC) is a major global cause of death among gynecological cancers, with a high mortality rate. Early diagnosis, distinguishing between benign conditions and early malignant OC forms, is vital for successful treatment. This research investigates serum metabolites to find diagnostic biomarkers for early OC identification.

Metabolomic profiles derived from the serum of 60 patients with benign conditions and 60 patients with malignant OC were examined using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Comparative analysis revealed differential metabolites linked to OC, aiding biomarker identification for early-diagnosis of OC via machine learning features. The predictive ability of these biomarkers was evaluated against the traditional biomarker, cancer antigen 125 (CA125).

84 differential metabolites were identified, including 2-Thiothiazolidine-4-carboxylic acid (TTCA), Methionyl-Cysteine, and Citrulline that could serve as potential biomarkers to identify benign conditions and malignant OC. In the diagnosis of early-stage OC, the area under the curve (AUC) for Citrulline was 0.847 (95 % Confidence Interval (CI): 0.719-0.974), compared to 0.770 (95 % CI: 0.596-0.944) for TTCA, and 0.754 for Methionine-Cysteine (95 % CI: 0.589-0.919). These metabolites demonstrate a superior diagnostic capability relative to CA125, which has an AUC of 0.689 (95 % CI: 0.448-0.931). Among these biomarkers, Citrulline stands out as the most promising. Additionally, in the diagnosis of benign conditions and malignant OC, using logistic regression to combine potential biomarkers with CA125 has an AUC of 0.987 (95 % CI: 0.9708-1) has been proven to be more effective than relying solely on the traditional biomarker CA125 with an AUC of 0.933 (95 % CI: 0.870-0.996). Furthermore, among all the differential metabolites, lipid metabolites dominate, significantly impacting glycerophospholipid metabolism pathway.

The discovered serum metabolite biomarkers demonstrate excellent diagnostic performance for distinguishing between benign conditions and malignant OC and for early diagnosis of malignant OC.

Chronic renal failure (CRF) is a severe syndrome affecting the urinary system for which there are no effective therapeutics. In this study, we investigate the effects and mechanisms of aminophylline in preventing CRF development. A rat model of chronic renal failure is established by 5/6 nephrectomy. The levels of serum creatinine (SCR), urinary protein (UPR), and blood urea nitrogen (BUN) are detected by ELISA. Histological evaluations of renal tissues are performed by H&E, Masson staining, and PAS staining. Functional protein expression is detected by western blot analysis or immunofluorescence microscopy. Glomerular cell apoptosis is determined using the TUNEL method. Results show that Aminophylline significantly reduces the levels of SCR, UPR, and BUN in the CRF model rats. Histological analyses show that aminophylline effectively alleviates renal tissue injuries in CRF rats. The protein expression levels of nephrin, podocin, SIRT1, p-AMPK, and p-ULK1 are greatly increased, while p-mTOR protein expression is markedly decreased by aminophylline treatment. Additionally, the protein level of LC3B in CRF rats is significantly increased by aminophylline. Moreover, aminophylline alleviates apoptosis in the glomerular tissues of CRF rats. Furthermore, resveratrol promotes SIRT1, p-AMPK, and p-ULK1 protein expressions and reduces p-mTOR and LC3B protein expressions in CRF rats. Selisistat (a SIRT1 inhibitor) mitigates the changes in SIRT1, p-AMPK, p-ULK1, p-mTOR, and LC3B expressions induced by aminophylline. Finally, RAPA alleviates renal injury and apoptosis in CRF rats, and 3-MA eliminates the aminophylline-induced inhibition of renal injury and apoptosis in CRF rats. Aminophylline suppresses chronic renal failure progression by modulating the SIRT1/AMPK/mTOR-mediated autophagy process.

The triglyceride-glucose (TyG) index, a simple surrogate marker of insulin resistance, is significantly associated with chronic kidney disease (CKD). However, there is limited research on the longitudinal trajectory of TyG index over time and its relationship with CKD.

To analyse the characteristics of the longitudinal trajectory of the TyG index over time and its association with the development of CKD in a health check-up population.

Participants who underwent at least three annual health check-ups at the Health Management Center of Sichuan Provincial People's Hospital from 2015 to 2022 were included in this retrospective cohort study. The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The latent class mixed model (LCMM) was used to identify the TyG index trajectory of the study population. A Cox proportional hazard model was used to estimate the CKD incidence risk in different quartile groups and the association of changes in the TyG index trajectory with the development of CKD.

A total of 4,921 participants were included in this study, and they were divided into four groups according to the quartiles of the baseline TyG index: Q1 (5.43-6.66), Q2 (6.67-7.04), Q3 (7.05-7.43), and Q4 (7.43-9.97). There was no difference in the risk of CKD occurrence among the TyG groups. Three different TyG index trajectories were identified in this study: a high-level group, middle-level stable group and low-level stable group, respectively. The incidence rate of CKD in the high-level TyG index trajectory group was 2.399 times greater than that in the low-level stable trajectory group (HR=2.399, 95% CI 1.167-4.935).

Individuals with long-term exposure to high TyG index levels had a significantly greater risk of CKD. Routine monitoring of the TyG index and its longitudinal trend will aid in the risk stratification of CKD in the general population and will be helpful for CKD prevention and targeted management.

Chronic kidney disease (CKD) is a multifactorial disease whose prevalence is increasing worldwide. CKD affects 700 million to 1 billion people worldwide, with a prevalence of 9.1% to 13.4%. In Iran, the reported prevalence of CKD is 15.14%, even higher than the global prevalence. Some studies introduced heavy metals as possible risk factors of CKD. We conducted the first study in Iran to examine the relationship between 10 selected urinary heavy metals and CKD in the Hovayzeh cohort study population.

In this cross-sectional study, urine samples were collected from two groups of ca ses (suffering from CKD) and controls (without CKD) with equal size (47 people each). Analysis of the 10 sellected heavy metals in the samples was conducted using inductively coupled plasma emission spectroscopy. Basic Information was obtained from the Howayizeh Cohort Study Center. The data was analyzed using SPSS-26 and Excel-2016 software.

There were no significant differences between urinary heavy metal concentrations of case and control groups (P < 0.05). While, the concentration of As, Cr, Cu, Mn, and Ni exceeded the reference limits of Germany, Canada, England, and Belgium. Se and Cd also surpassed the reference limits of England. After adjusting for confounding variables for each μg/l increase in urinary Cd, Ni, Pb, and Se the OR of CKD increased by 20.2%, 4.8%, 3.1%, and 2.6%, respectively. Although, these relationships were not statistically significant. In addition, two groups of heavy metals had a positive and significant correlation: (1) Se, Zn, As, Cu, and Cr; (2) Pb, Cd, and As; and (3) Cd and Ni.

we found no significant relationship between urinary heavy metal and CKD. However, there was significant positive correlation in some of urinary heavy metals may indicate their shared resources. Furthermore, the concentration of most heavy metals in the urine of the participants was higher than the reference limits of these metals in the urine of healthy people from other countries. Thus, the elevated levels of these metals could still pose a risk to human health. Therefore, it is necessary to conduct prospective studies with a larger sample size in this area.

The prevalence of chronic kidney disease (CKD) is high. Identification of cases with CKD or at high risk of developing it is important to tailor early interventions. The objective of this study was to identify blood metabolites associated with prevalent and incident severe CKD, and to quantify the corresponding improvement in CKD detection and prediction.

Data from four cohorts were analyzed: Singapore Epidemiology of Eye Diseases (SEED) (n = 8802), Copenhagen Chronic Kidney Disease (CPH) (n = 916), Singapore Diabetic Nephropathy (n = 714), and UK Biobank (UKBB) (n = 103,051). Prevalent CKD (stages 3-5) was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2; incident severe CKD as CKD-related mortality or kidney failure occurring within 10 years. We used multivariable regressions to identify, among 146 blood metabolites, those associated with CKD, and quantify the corresponding increase in performance.

Chronic kidney disease prevalence (stages 3-5) and severe incidence were 11.4% and 2.2% in SEED, and 2.3% and 0.2% in UKBB. Firstly, phenylalanine (Odds Ratio [OR] 1-SD increase = 1.83 [1.73, 1.93]), tyrosine (OR = 0.75 [0.71, 0.79]), docosahexaenoic acid (OR = 0.90 [0.85, 0.95]), citrate (OR = 1.41 [1.34, 1.47]) and triglycerides in medium high density lipoprotein (OR = 1.07 [1.02, 1.13]) were associated with prevalent stages 3-5 CKD. Mendelian randomization analyses suggested causal relationships. Adding these metabolites beyond traditional risk factors increased the area under the curve (AUC) by 3% and the sensitivity by 7%. Secondly, lactate (HR = 1.33 [1.08, 1.64]) and tyrosine (HR = 0.74 [0.58, 0.95]) were associated with incident severe CKD among individuals with eGFR < 90 mL/min/1.73 m2 at baseline. These metabolites increased the c-index by 2% and sensitivity by 5% when added to traditional risk factors.

The performance improvements of CKD detection and prediction achieved by adding metabolites to traditional risk factors are modest and further research is necessary to fully understand the clinical implications of these findings.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive tumor mainly affecting children and adolescents. It is driven by multiple genetic mutations that together define the leukemic phenotype. Interestingly, based on genetic alterations and/or deregulated expression, at least six genetic subgroups have been recognized. The TAL/LMO subgroup is one of the most represented genetic subgroups, characterizing 30-45% of pediatric T-ALL cases. The study of lipid and metabolic profiles is increasingly recognized as a valuable tool for comprehending the development and progression of tumors. In this study, metabolic and lipidomic analysis via LC/MS have been carried out on four T-ALL cell lines belonging to the TAL/LMO subgroup (Jurkat, Molt-4, Molt-16, and CCRF-CEM) to identify new potential metabolic biomarkers and to provide a subclassification of T-ALL cell lines belonging to the same subgroup. A total of 343 metabolites were annotated, including 126 polar metabolites and 217 lipid molecules. The statistical analysis, for both metabolic and lipid profiles, shows significant differences and similarities among the four cell lines. The Molt-4 cell line is the most distant cell line and CCRF-CEM shows a high activity in specific pathways when compared to the other cell lines, while Molt-16 and Jurkat show a similar metabolic profile. Additionally, this study highlighted the pathways that differ in each cell line and the possible enzymes involved using bioinformatic tools, capable of predicting the pathways involved by studying the differences in the metabolic profiles. This experiment offers an approach to differentiate T-ALL cell lines and could open the way to verify and confirm the obtained results directly in patients.

Kidney disease remains a condition with an increasing incidence, high morbidity and mortality associated with cardiovascular events. The incidence of end-stage renal disease is expected to increase. Despite of the technical improvement, dialysis never achieved a full clearance of the blood dialysis. Therefore, the demand for new renoprotective measures has never been greater. Here, we report new strategies for preventing renal damage.

Chronic kidney disease (CKD) is a major public health burden, with dietary acid load (DAL) and gut microbiota playing crucial roles. As DAL can affect the host metabolome, potentially via the gut microbiota, we cross-sectionally investigated the interplay between DAL, host metabolome, gut microbiota, and early-stage CKD (TwinsUK, n = 1,453). DAL was positively associated with CKD stage G1-G2 (Beta (95% confidence interval) = 0.34 (0.007; 0.7), p = 0.046). After adjusting for covariates and multiple testing, we identified 15 serum, 14 urine, 8 stool, and 7 saliva metabolites, primarily lipids and amino acids, associated with both DAL and CKD progression. Of these, 8 serum, 2 urine, and one stool metabolites were found to mediate the DAL-CKD association. Furthermore, the stool metabolite 5-methylhexanoate (i7:0) correlated with 26 gut microbial species. Our findings emphasize the gut microbiota's therapeutic potential in countering DAL's impact on CKD through the host metabolome. Interventional and longitudinal studies are needed to establish causality.

It is still a serious public health issue that chronic kidney disease of uncertain etiology (CKDu) in Sri Lanka poses challenges in identification, prevention, and treatment. What environmental factors in drinking water cause kidney damage remains unclear. This study aimed to investigate the risks of various environmental factors that may induce CKDu, including water hardness, fluoride (HF), heavy metals (HM), microcystin-LR (MC-LR), and their combined exposure (HFMM). The research focused on comprehensive metabolome analysis, and correlation with transcriptomic and gut microbiota changes. Results revealed that chronic exposure led to kidney damage and pancreatic toxicity in adult zebrafish. Metabolomics profiling showed significant alterations in biochemical processes, with enriched metabolic pathways of oxidative phosphorylation, folate biosynthesis, arachidonic acid metabolism, FoxO signaling pathway, lysosome, pyruvate metabolism, and purine metabolism. The network analysis revealed significant changes in metabolites associated with renal function and diseases, including 20-Hydroxy-LTE4, PS(18:0/22:2(13Z,16Z)), Neuromedin N, 20-Oxo-Leukotriene E4, and phenol sulfate, which are involved in the fatty acyls and glycerophospholipids class. These metabolites were closely associated with the disrupted gut bacteria of g_ZOR0006, g_Pseudomonas, g_Tsukamurella, g_Cetobacterium, g_Flavobacterium, which belonged to dominant phyla of Firmicutes and Proteobacteria, etc., and differentially expressed genes (DEGs) such as egln3, ca2, jun, slc2a1b, and gls2b in zebrafish. Exploratory omics analyses revealed the shared significantly changed pathways in transcriptome and metabolome like calcium signaling and necroptosis, suggesting potential biomarkers for assessing kidney disease.

Heart failure (HF) has been recognized as a global epidemic with high rates of morbidity, hospitalization, and mortality. The role of amino acids, which provide the body with energy, in the development of HF is still unclear. The aim of this study was to explore changes in serum amino acids in patients with HF and identify potential biomarkers. First, the serum amino acid metabolism profiles of 44 patients with HF and 30 healthy controls (Con) were quantitatively measured. Then, candidate markers were identified through the utilization of T test, multivariate statistical analysis, and receiver operating characteristic (ROC) curve analysis. The results found that there were 11 amino acid levels that were significantly different between patients with HF and Con. Based on ROC curve analysis, the biomarkers of eight amino acids (Glutamic acid, Taurine, L-aspartic acid, L-ornithine, Ethanolamine, L-Serine, L-Sarcosine, and Cysteine) showed high sensitivity and specificity (AUC > 0.90), and binary logistic regression analysis was used in MetaboAnalyst 5.0. Among the amino acids examined, six exhibited notable alterations in accordance with the severity of HF. In conclusion, this study cannot only provide clinicians with an objective diagnostic approach for the early identification of HF, but also enhances comprehension of the underlying mechanisms involved in the pathogenesis of HF.

The role of co-agonists of glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) in chronic kidney disease (CKD) remains unclear. Herein we found that GLP-1R and GCGR expression levels were lower in the kidneys of mice with CKD compared to healthy mice and were correlated with disease severity. Interestingly, GLP-1R or GCGR knockdown aggravated the progression of kidney injury in both diabetic db/db mice and non-diabetic mice undergoing unilateral ureteral obstruction (UUO). Based on the importance of GLP-1R and GCGR in CKD, we reported a novel monomeric peptide, 1907-B, with dual-agonism on both GLP-1R and GCGR. The data confirmed that 1907-B had a longer half-life than long-acting semaglutide in rats or cynomolgus monkeys (∼2-3 fold) and exhibited better therapeutic contribution to CKD than best-in-class monoagonists, semaglutide, or glucagon, in db/db mice and UUO mice. Various lock-of-function models, including selective pharmacological activation and genetic knockdown, confirmed that 1907-B's effects on ameliorating diabetic nephropathy in db/db mice, as well as inhibiting kidney fibrosis in UUO mice, were mediated through GLP-1 and glucagon signaling. These findings highlight that 1907-B, a novel GLP-1R and GCGR co-agonist, exerts multifactorial improvement in kidney injuries and is an effective and promising therapeutic option for CKD treatment.

Chronic kidney disease (CKD) is a major public health concern. However, validated and broadly applicable biomarkers for early CKD diagnosis are currently not available. We aimed to identify serum metabolic signatures at an early stage of CKD to provide a reference for future investigations into the early diagnostic biomarkers.

Serum metabolites were extracted from 65 renal dysfunction (RD) patients and 121 healthy controls (discovery cohort: 12 RD patients and 55 health participants; validation cohort: 53 RD patients and 66 health participants). Metabolite extracts were analyzed by ultraperformance liquid chromatography coupled with quadrupole-electrostatic field orbital trap mass spectrometry (UPLC-QE-Orbitrap MS) for untargeted metabolomics. Orthogonal partial least squares-discriminant analysis (OPLS-DA) was performed to detect different compounds between groups. Receiver operating characteristic (ROC) curve analysis was carried out to determine the diagnostic value of the validated differential metabolites between groups. We referred to the Kyoto Encyclopedia of Gene and Genomes (KEGG) to elucidate the metabolic pathways of the validated differential metabolites.

A total of 22 and 23 metabolites had significantly different abundances in the discovery and validation cohort, respectively. Six of them (creatinine, L-proline, citrulline, butyrylcarnitine, 1-methylhistidine, and valerylcarnitine) in the RD group was more abundant than that of the health group in both cohorts. The combination of the six validated differential metabolites were able to accurately detect RD (AUC 0.86). Three of the six metabolites are involved in the metabolism of arginine and proline.

The present study highlights that creatinine, L-proline, citrulline, butyrylcarnitine, 1-methylhistidine, and valerylcarnitine are metabolite indicators with potential predictive value for CKD.

Despite observations of decreased ANGPTL3 (angiopoietin-like protein 3) levels in tubular atrophy and renal interstitial fibrosis (RIF), its functional implications and regulatory mechanisms in RIF remain unclear. This investigation employed unilateral ureteral obstruction (UUO) mice as in vivo model and human proximal kidney tubuloepithelial HK-2 cells under TGF-β1 treatment as in vitro model to explore RIF. The RIF extent was evaluated using H & E staining and Masson's trichrome staining. There was a significant decrease in ANGPTL3 levels and an increase in miR-144-3p, accompanied by heightened expressions of α-SMA, p-PI3K, p-AKT, Collagen I, and Fibronectin in the UUO mice and HK-2 cells treated with TGF-β1. Enhancing ANGPTL3 expression or suppressing miR-144-3p mitigated TGF-β1-induced cellular apoptosis, inflammation, and PI3K/AKT signaling pathway activation, as evidenced by altered levels of α-SMA, Collagen I, Fibronectin, and associated signaling markers. Using a bioinformatics approach, a miR-144-3p binding site was discovered on the ANGPTL3 mRNA, and this finding was subsequently confirmed through luciferase reporter assay. In HK-2 cells stimulated with TGF-β1, the suppression of ANGPTL3 negated the effects of inhibiting miR-144-3p. Under comparable conditions, the use of LY294002, an inhibitor of the PI3K/AKT pathway, nullified the effects caused by the knockdown of ANGPTL3. Collectively, these findings indicate that miR-144-3p exacerbates RIF through PI3K/AKT pathway activation by targeting ANGPTL3, highlighting a novel potential therapeutic target for RIF management.

Purine intermediates play important roles in physiological function and participate in the kidney disorders, while a targeted quantification of the metabolic alterations in the purine metabolism in acute kidney injury (AKI) individuals has not been conducted. In the study, a novel, rapid and sensitive LC-MS method for simultaneous quantification of 16 purine metabolites was developed using hydrophilic interaction separation mode in human plasma and urine. The developed method was validated by using charcoal-stripped plasma and urine as blank matrix. The results showed that the method was good linear (R2 > 0.99) and the lower limit of quantification (LLOQ) ranged from 0.833 ng/mL to 800 ng/mL. The recovery and matrix effect were repeatable and stable. The intraday precision ranged from 0.7% to 12.7%, while the inter-day precision ranged from 1.6% to 18.5%. Most analytes were stable in the autosampler and could subject three freeze-thaw cycles. The method provided a wider coverage of purine metabolites and completed good separation of interfering compounds of nucleosides, deoxynucleosides and their corresponding nucleobases without derivatization, which was time-saving and labor-saving for the large-scale analysis. Furthermore, the method was successfully applied to plasma and urine samples of hospitalized patients without and with AKI. The results showed certain purine intermediates were up-regulated in plasma and down-regulated in urine of AKI inpatients, indicating that AKI stress may associate with inflammatory responses. The novel method can facilitate the quantitative analysis of purine metabolites in biological fluids, and exhibit great prospects in providing more information on the pathogenesis of AKI.

Chronic kidney disease (CKD) is a widespread ailment that significantly impacts global health. It is characterized by high prevalence, poor prognosis, and substantial healthcare costs, making it a major public health concern. The current clinical treatments for CKD are not entirely satisfactory, leading to a high demand for alternative therapeutic options. Chinese herbal medicine, with its long history, diverse varieties, and proven efficacy, offers a promising avenue for exploration. One such Chinese herbal medicine, Dioscorea nipponica Makino (DNM), is frequently used to treat kidney diseases. In this review, we have compiled studies examining the mechanisms of action of DNM in the context of CKD, focusing on five primary areas: improvement of oxidative stress, inhibition of renal fibrosis, regulation of metabolism, reduction of inflammatory response, and regulation of autophagy.