Search Results (127)

Hyperuricemia (HUA), a metabolic disorder characterized by elevated serum uric acid (UA) levels, often leads to renal and hepatic complications. This study evaluated the synergistic effects of Pediococcus acidilactici GQ01, a probiotic strain isolated from naturally fermented wolfberry, in combination with a complex (T) composed of buckwheat-fermented postbiotics, collagen peptide and multiple medicinal food blends in a murine HUA model. The combination therapy (T + GQ01) not only significantly reduced serum UA levels more effectively than T or GQ01 alone but also demonstrated superior inhibition of XOD activity and enhanced ADA activity, both of which are key regulators of purine metabolism. Additionally, T + GQ01 ameliorated kidney injury, as evidenced by reduced serum CRE and BUN levels, and improved liver function, indicated by decreased ALT and AST activities. Histopathological analysis further confirmed the protective effects of T + GQ01 on renal and hepatic tissues. Moreover, T + GQ01 modulated intestinal flora composition, promoted beneficial genera such as Weissella and Bacteroides, and enhanced the production of SCFAs, particularly propionic and butyric acids, which play critical roles in maintaining intestinal health. These findings suggest that the cocktail-like microecological regulator combining P. acidilactici GQ01, buckwheat-fermented postbiotics, collagen peptide and multiple medicinal food blends represents a promising therapeutic strategy for HUA by targeting multiple metabolic pathways, underscoring its potential as a novel intervention for HUA and its complications. Full article

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), previously referred to as Non-Alcoholic Fatty Liver Disease (NAFLD), is a prevalent chronic liver condition strongly linked to Type 2 Diabetes Mellitus (T2DM) and obesity. Globally, MASLD is the most common cause of chronic liver disease. The bidirectional relationship between MASLD and T2DM underscores the pivotal role of insulin resistance in disease progression, which contributes to hepatic steatosis, oxidative stress, and inflammation, forming a vicious cycle. MASLD is also associated with heightened risks of cardiovascular and chronic kidney diseases, necessitating comprehensive treatment approaches. While lifestyle interventions and weight loss remain the cornerstone of management, their sustainability is challenging. This review highlights the evolving pharmacological landscape targeting MASLD and its advanced form, Metabolic Dysfunction-Associated Steatohepatitis (MASH). Currently, Resmetirom is the only FDA-approved drug for MASH. Current and investigational therapies, including insulin-sensitizing agents like peroxisome proliferator-activated receptor (PPAR) agonists, glucose-lowering drugs such as sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA), drugs that target intermediary metabolism such as Vitamin E, de novo lipogenesis inhibitors, and emerging agents targeting the gut-liver axis and oxidative stress, are explored. These therapies demonstrate promising effects on hepatic steatosis, inflammation, and fibrosis, providing new avenues to address the multifaceted pathophysiology of MASLD. Full article

Obesity and type 2 diabetes mellitus (T2DM) are global health crises with significant morbidity and mortality. Retatrutide, a novel triple receptor agonist targeting glucagon-like peptide-1 (GLP-1), Glucose-Dependent Insulinotropic Polypeptide (GIP), and glucagon receptors, represents a groundbreaking advancement in obesity and T2DM pharmacotherapy. This review synthesizes findings from preclinical and clinical studies, highlighting retatrutide’s mechanisms, efficacy, and safety profile. Retatrutide’s unique molecular structure enables potent activation of GLP-1, GIP, and glucagon receptors, leading to significant weight reduction, improved glycemic control, and favorable metabolic outcomes. Animal studies demonstrate retatrutide’s ability to delay gastric emptying, reduce food intake, and promote weight loss, with superior efficacy compared to other incretin-based therapies. Phase I and II clinical trials corroborate these findings, showing dose-dependent weight loss, reductions in Glycated Hemoglobin (HbA1c) levels, and improvements in liver steatosis and diabetic kidney disease. Common adverse effects are primarily gastrointestinal and dose-related. Ongoing Phase III trials, such as the TRIUMPH studies, aim to further evaluate retatrutide’s long-term safety and efficacy in diverse patient populations. While retatrutide shows immense promise, considerations regarding cost and the quality of weight loss beyond BMI reduction warrant further investigation. Retatrutide heralds a new era in obesity and T2DM treatment, offering hope for improved patient outcomes. Full article

Cisplatin (CIS) is a widely used chemotherapeutic agent that is highly effective against various cancers. However, its clinical application is frequently limited by its substantial nephrotoxic side effects. The gastrin-releasing peptide receptor (GRPR), a critical regulator in inflammatory diseases, has been identified as a promising therapeutic target. Our previous studies have demonstrated that the GRPR antagonists PD176252 and RH-1402 can mitigate CIS-induced nephrotoxicity through anti-inflammatory mechanisms. Based on these findings, we designed and synthesized a series of 2-arylpropanoic acid-L-tryptophan derivatives to enhance the therapeutic effects. Among these compounds, 3m exhibited superior renal protection by significantly improving mouse renal tubular epithelial cell (mRTEC) viability from 50.2 ± 2.6% to 80.5 ± 3.9%, surpassing PD176252 (70.8 ± 1.4%) and RH-1402 (73.9 ± 3.7%). Moreover, compound 3m markedly reduced the expression of kidney injury molecule-1 (KIM-1) and inflammatory cytokines [Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), Monocyte Chemoattractant Protein-1 (MCP-1)]. Finally, molecular docking results revealed that 3m exhibited a high binding affinity for GRPR. Computational predictions using SwissADME further indicated that 3m possesses favorable drug-like properties, thereby supporting its potential as a promising candidate for mitigating CIS-induced nephrotoxicity. Full article

Background/Objectives: The kidney plays a crucial role in regulating normal blood pressure and is one of the major organs affected by hypertension. The present study aimed to investigate the hypotensive and renoprotective effects of four specific green tea peptides extracted from green tea dregs on spontaneously hypertensive rats (SHRs) and to investigate the underlying mechanisms. Methods: Four specific green tea peptides (40 mg/kg) were gavaged to SHRs for 4 weeks, and blood pressure, renal function, renal pathological changes, renal tissue fibrosis indexes, and inflammation indexes were examined in SHRs to analyze the role of the four green tea peptides in alleviating hypertension and its renal injury. Results: The results showed that the four TPs significantly reduced systolic and diastolic blood pressure (20–24% and 18–28%) in SHR compared to the model group. Meanwhile, gene levels and protein expression of renal fibrosis-related targets such as phospho-Smad2/3 (p-Smad2/3) (26–47%), Sma- and Mad-related proteins 2/3 (Smad2/3) (19–38%), transforming growth factor-β1 (TGF-β1) (36–63%), and alpha-smooth muscle actin (alpha-SMA) (58–86%) were also significantly reduced. In addition, the reduced expression levels of medullary differentiation factor 88 (MyD88) (14–36%), inducible nitric oxide synthase (iNOS) (58–73%), and nuclear factor-κB p65 (NF-kB p65) (35–78%) in kidneys also confirmed that TPs attenuated renal inflammation in SHR. Therefore, green tea peptides could attenuate the fibrosis and inflammatory responses occurring in hypertensive kidneys by inhibiting the Ang II/TGF-β1/SMAD signaling pathway and MyD88/NF-κB p65/iNOS signaling pathway. Conclusions: The results showed that green tea peptides may be effective candidates for lowering blood pressure and attenuating kidney injury. Full article

Fibrosis, characterized by excessive extracellular matrix (ECM) deposition, disrupts tissue architecture and impairs organ function, ultimately leading to severe health consequences and even failure of vital organs such as the lung, heart, liver, and kidney. Despite significant advances in understanding the molecular mechanisms underlying fibrosis, effective therapeutic options remain limited. Emerging evidence highlights scaffold proteins as critical regulators in the progression of fibrosis. These multifunctional proteins serve as molecular platforms that organize and coordinate key signaling pathways—including those governing ECM remodeling, cytoskeletal organization, and cell migration—thereby integrating both profibrotic and antifibrotic signals. Their pivotal role in linking mechanotransduction, inflammatory, and developmental signals offers a unique therapeutic window, as targeted interventions (e.g., small-molecule inhibitors, peptides, biologics, and gene therapy) are emerging to modulate these pathways. This review synthesizes recent findings on scaffold protein functions across multiple organs and discusses novel therapeutic strategies to manage and potentially reverse fibrosis. Full article

Fabry disease (FD) is an X-linked lysosomal storage disorder characterized by deficiency of α-galactosidase A (α-GalA), leading to the accumulation of glycosphingolipids and multi-organ dysfunction, particularly affecting the cardiovascular and renal systems. Disease-modifying treatments such as enzyme replacement therapy (ERT) and oral chaperone therapy (OCT) have limited efficacy, particularly in advanced disease, prompting a need for innovative therapeutic approaches targeting underlying molecular mechanisms beyond glycosphingolipid storage alone. Recent insights into the pathophysiology of FD highlights chronic inflammation and mitochondrial, lysosomal, and endothelial dysfunction as key mediators of disease progression. Adjunctive therapies such as sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) agonists, and mineralocorticoid receptor antagonists (MRAs) demonstrate significant cardiovascular and renal benefits in conditions including heart failure and chronic kidney disease. These drugs also modulate pathways involved in the pathophysiology of FD, such as autophagy, oxidative stress, and pro-inflammatory cytokine signaling. While theoretical foundations support their utility, dedicated trials are necessary to confirm efficacy in the FD-specific population. This narrative review highlights the importance of expanding therapeutic strategies in FD, advocating for a multi-faceted approach involving evidence-based adjunctive treatments to improve outcomes. Tailored research focusing on diverse FD phenotypes, including females and non-classical variants of disease, will be critical to advancing care and improving outcomes in this complex disorder. Full article

The overexpression of the epidermal growth factor receptor (EGFR) in certain types of prostate cancers and glioblastoma makes it a promising target for targeted radioligand therapy. In this context, pairing an EGFR-targeting peptide with the emerging theranostic pair comprising the Auger electron emitter cobalt-58m (^58mCo) and the Positron Emission Tomography-isotope cobalt-55 (⁵⁵Co) would be of great interest for creating novel radiopharmaceuticals for prostate cancer and glioblastoma theranostics. In this study, GE11 (YHWYGYTPQNVI) was investigated for its EGFR-targeting potential when conjugated using click chemistry to N1-((triazol-4-yl)methyl)-N1,N2,N2-tris(pyridin-2-ylmethyl)ethane-1,2-diamine (TZTPEN). This chelator is suitable for binding Co²⁺ and Co³⁺. With cobalt-57 (⁵⁷Co) serving as a surrogate radionuclide for ^55/58mCo, the novel GE11-TZTPEN construct was successfully radiolabeled with a high radiochemical yield (99%) and purity (>99%). [⁵⁷Co]Co-TZTPEN-GE11 showed high stability in PBS (pH 5) and specific uptake in EGFR-positive cell lines. Disappointingly, no tumor uptake was observed in EGFR-positive tumor-bearing mice, with most activity being accumulated predominantly in the liver, gall bladder, kidneys, and spleen. Some bone uptake was also observed, suggesting in vivo dissociation of ⁵⁷Co from the complex. In conclusion, [⁵⁷Co]Co-TZTPEN-GE11 shows poor pharmacokinetics in a mouse model and is, therefore, not deemed suitable as a targeting radiopharmaceutical for EGFR. Full article

Chronic kidney disease (CKD) is a progressive condition characterized by declining renal function, with limited biomarkers to predict its progression. The early identification of prognostic biomarkers is crucial for improving patient care and therapeutic strategies. This follow-up study investigated urinary proteomics and clinical outcomes in 18 CKD patients (stages 1–3) and 15 healthy controls using liquid chromatography–mass spectrometry and Mascot-SwissProt for protein identification. The exponentially modified protein abundance index (emPAI) was used for peptide quantification. Regression analyses were used to evaluate relationships between urinary proteins and the estimated glomerular filtration rate (eGFR), adjusting for proteinuria. At baseline, 171 proteins (median emPAI 86) were identified in CKD patients, and 271 were identified (median emPAI 47) in controls. At follow-up, 285 proteins (median emPAI 44.8) were identified in CKD patients, and 252 were identified (median emPAI 34.2) in controls. FBN1 was positively associated with eGFR, while FETUA showed a significant negative correlation at baseline. At follow-up, VTDB shifted from a negative baseline to a positive association with eGFR over time. CD44 and FBN1 shifted from a positive baseline to a negative association over time. These findings highlight VTDB, FBN1, and CD44 as potential prognostic biomarkers, providing insights into CKD progression and therapeutic targets. Full article

Hyperuricemia, a disorder of purine metabolism associated with cardiovascular disease, gout, and kidney disease, can be alleviated by food-derived peptides. However, the precise mechanisms remain unclear, hindering their development. This study reviews uric acid-lowering peptides from various sources, focusing on two pathways: inhibiting uric acid production and promoting excretion. Low-molecular-weight peptides (<1000 Da) exhibited superior uric acid-lowering effects. We further explored the relationships between amino acid composition and their target interactions. Peptides rich in cyclic amino acids (tryptophan, phenylalanine, and histidine) and containing small amounts of linear amino acids (leucine, cysteine, and glycine) demonstrated significant potential for lowering uric acid. These findings provide theoretical support for developing novel functional foods for the management of hyperuricemia. Full article

This comprehensive review explores the biological functions of Perilla frutescens seed proteins and peptides, highlighting their significant potential for health and therapeutic applications. This review delves into the mechanisms through which perilla peptides combat oxidative stress and protect cells from oxidative damage, encompassing free radical scavenging, metal chelating, in vivo antioxidant, and cytoprotective activities. Perilla peptides exhibit robust anti-aging properties by activating the Nrf2 pathway, enhancing cellular antioxidant capacity, and supporting skin health through the promotion of keratinocyte growth, maintenance of collagen integrity, and reduction in senescent cells. Additionally, they demonstrate antidiabetic activity by inhibiting α-amylase and α-glucosidase. The cardioprotective effects of perilla peptides are underscored by ACE-inhibitory activities and combat oxidative stress through enhanced antioxidant defenses. Further, perilla peptides contribute to improved gut health by enhancing beneficial gut flora and reinforcing intestinal barriers. In liver, kidney, and testicular health, they reduce oxidative stress and apoptotic damage while normalizing electrolyte levels and protecting against cyclophosphamide-induced reproductive and endocrine disruptions by restoring hormone synthesis. Promising anticancer potential is also demonstrated by perilla peptides through the inhibition of key cancer cell lines, alongside their anti-inflammatory and immunomodulating activities. Their anti-fatigue effects enhance exercise performance and muscle function, while perilla seed peptide nanoparticles show potential for targeted drug delivery. The diverse applications of perilla peptides support their potential as functional food additives and therapeutic agents. Full article

Neuropeptide FF (NPFF) is an endogenous octapeptide that was originally isolated from the bovine brain. It belongs to the RFamide family of peptides that has a wide range of physiological functions and pathophysiological effects. NPFF and its receptors, NPFFR1 and NPFFR2, abundantly expressed in rodent and human brains, participate in cardiovascular regulation. However, the expressions of NPFF and its receptors are not restricted within the central nervous system but are also found in peripheral organs, including the kidneys. Both NPFFR1 and NPFFR2 mainly couple to Gαi/o, which inhibits cyclic adenosine monophosphate (cAMP) production. NPFF also weakly binds to other RFamide receptors and the Mas receptor. Relevant published articles were searched in PubMed, Google Scholar, Web of Science, and Scopus. Herein, we review evidence for the role of NPFF in the regulation of blood pressure, in the central nervous system, particularly within the hypothalamic paraventricular nucleus and the brainstem, and the kidneys. NPFF is a potential target in the treatment of hypertension. Full article

Kidney disease is a public health epidemic affecting 10% of the population worldwide with a constantly rising incidence, and it is an important contributor to morbidity and mortality. Type 2 diabetes mellitus (T2DM) is a chronic complex condition with a rising incidence worldwide. T2DM remains the principal cause of chronic kidney disease (CKD), which is related to a high risk for cardiovascular (CV) events, end-stage kidney disease (ESKD), and, overall, considerable morbidity and mortality. In the past few decades, various therapeutic treatments have targeted the culprit pathways for slowing CKD progression, with partial success. Thus, despite new advances in patients’ treatment, progressive loss of kidney function or death from T2DM and CKD complications compel new therapeutic pathways. Renin–angiotensin–aldosterone-system-blocking agents have been the only treatment until recently. On top of this, sodium–glucose co-transporter 2 inhibitors along with finerenone showed an impressive ability to reduce the progression of kidney disease and cardiovascular events in diabetic patients with CKD. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) can play a special role and could be a game changer in this field. The latest FLOW trial confirmed multiple favorable clinical effects on renal, cardiovascular, and survival outcomes among high-risk patients treated with semaglutide and supports a significant therapeutic role for GLP-1RAs in this population, although larger-scale evaluation of their risks is needed, given their increasing use. Full article

Contrast-induced acute kidney injury (CIAKI) is a common complication with limited treatments. Intermedin (IMD), a peptide belonging to the calcitonin gene-related peptide family, promotes vasodilation and endothelial stability, but its role in mitigating CIAKI remains unexplored. This study investigates the protective effects of IMD in CIAKI, focusing on its mechanisms, particularly the cAMP/Rac1 signaling pathway. Human umbilical vein endothelial cells (HUVECs) were treated with iohexol to simulate kidney injury in vitro. The protective effects of IMD were assessed using CCK8 assay, flow cytometry, ELISA, and Western blotting. A CIAKI rat model was utilized to evaluate renal peritubular capillary endothelial cell injury and renal function through histopathology, immunohistochemistry, immunofluorescence, Western blotting, and transmission electron microscopy. In vitro, IMD significantly enhanced HUVEC viability and mitigated iohexol-induced toxicity by preserving intercellular adhesion junctions and activating the cAMP/Rac1 pathway, with Rac1 inhibition attenuating these protective effects. In vivo, CIAKI caused severe damage to peritubular capillary endothelial cell junctions, impairing renal function. IMD treatment markedly improved renal function, an effect negated by Rac1 inhibition. IMD protects against renal injury in CIAKI by activating the cAMP/Rac1 pathway, preserving peritubular capillary endothelial integrity and alleviating acute renal injury from contrast media. These findings suggest that IMD has therapeutic potential in CIAKI and highlight the cAMP/Rac1 pathway as a promising target for preventing contrast-induced acute kidney injury in at-risk patients, ultimately improving clinical outcomes. Full article

Diabetic kidney disease (DKD) is a major complication of diabetes mellitus (DM), affecting over one-third of type 1 and nearly half of type 2 diabetes patients. As the leading cause of end-stage renal disease (ESRD) globally, DKD develops through a complex interplay of chronic hyperglycemia, oxidative stress, and inflammation. Early detection is crucial, with diagnosis based on persistent albuminuria and reduced estimated glomerular filtration rate (eGFR). Treatment strategies emphasize comprehensive management, including glycemic control, blood pressure regulation, and the use of nephroprotective agents such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), sodium-glucose cotransporter-2 (SGLT2) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists. Ongoing research explores novel therapies targeting molecular pathways and non-coding RNAs. Preventive measures focus on rigorous control of hyperglycemia and hypertension, aiming to mitigate disease progression. Despite therapeutic advances, DKD remains a leading cause of ESRD, highlighting the need for continued research to identify new biomarkers and innovative treatments. Full article