Early diagnosis and treatment of rheumatoid arthritis (RA) are essential to reducing disability. However, the diagnostic criteria remain unclear, relying on clinical symptoms and blood markers.

Using high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) targeted detection, we evaluated 76 carnitine indicators (55 carnitines and 21 corresponding ratios) in the serum of patients with RA to investigate the role of carnitine in RA. A total of 359 patients (207 patients with RA and 152 healthy controls) were included in the study. Screening involved three methods and integrated 76 carnitine indicators and 128 clinical indicators to identify candidate markers to establish a theoretical basis for RA diagnosis and new therapeutic targets. The diagnostic model derived from the screened markers was validated using three machine learning algorithms.

The model was refined using eight candidate indicators (C0, C10:1, LYMPH, platelet distribution width, anti-keratin antibody, glucose, urobilinogen, and erythrocyte sedimentation rate (ESR)). The receiver operating characteristic curve, sensitivity, specificity, and accuracy of the V8 model obtained from the training set were >0.948, 79.46%, 92.99%, and 89.18%, whereas those of the test set were >0.925, 78.89%, 89.22%, and 85.87%, respectively. Twenty-four carnitines were identified as risk factors of RA, with three significantly correlating with ESR, four with anti-cyclic citrullinated peptide antibody activity, two with C-reactive protein, five with immunoglobulin-G, eight with immunoglobulin-A levels, and eleven with immunoglobulin-M levels.

Carnitine is integral in the progression of RA. The diagnostic model developed shows excellent diagnostic capacity, improving early detection and enabling timely intervention to minimize disability associated with RA.

Traditionally, the carnitine pool is closely related to fatty acid metabolism. However, with increasing research, the pleiotropic effects of the carnitine pool have gradually emerged. The purpose of this review is to comprehensively investigate of the emerging understanding of the pleiotropic role of the carnitine pool, carnitine/acylcarnitines are not only auxiliaries or metabolites of fatty acid oxidation, but also play more complex and diverse roles, including energy metabolism, mitochondrial homeostasis, epigenetic regulation, regulation of inflammation and the immune system, tumor biology, signal transduction, and neuroprotection. This review provides an overview of the complex network of carnitine synthesis, transport, shuttle, and regulation, carnitine/acylcarnitines have the potential to be used as communication molecules, biomarkers and therapeutic targets for multiple diseases, with profound effects on intercellular communication, metabolic interactions between organs and overall metabolic health. The purpose of this review is to comprehensively summarize the multidimensional biological effects of the carnitine pool beyond its traditional role in fatty acid oxidation and to summarize the systemic effects mediated by carnitine/acylcarnitine to provide new perspectives for pharmacological research and treatment innovation and new strategies for the prevention and treatment of a variety of diseases.

Renal toxicity is a disorder that causes considerable issues in healthcare systems world, highlighting the critical importance of creating alternative treatments. Metallic nanoparticles have recently emerged as promising therapeutic agents for nephroprotection because of their remarkable properties. Numerous disciplines, including medicine, biotechnology, and the food industry, are currently investigating and exploring metallic nanoparticles, such as selenium, silver, and gold, with promising outcomes. In this overview, we provide the most current findings on cutting-edge nephroprotection through metallic nanoparticles, especially selenium, silver, and gold nanoparticles. While outlining the benefits, we outline possible methods for developing metallic nanoparticles, characterization techniques, and nephroprotection therapies. Selenium nanoparticles (SeNPs) minimize oxidative stress, a primary cause of nephrotoxicity through cell regeneration which protects kidneys. Silver nanoparticles (AgNPs) have anti-inflammatory capabilities that help alleviate kidney damage and nephrotoxicity. Gold nanoparticles (AuNPs), which are biocompatible and immune-modifying, reduce inflammation and promote renal cell regeneration, indicating nephroprotective advantages. Renal protection via the use of metallic nanoparticles represents a promising new frontier in the fight against kidney disease and other renal disorders. Metallic nanoparticles of selenium, silver, and gold can protect the kidneys by lowering oxidative stress, reducing inflammation, and improving cell repair. Through their mechanisms, these nanoparticles effectively safeguard and repair kidney function, making them suitable for treating renal diseases. The potential applications of selenium, silver, and gold nanoparticles, as well as their complex modes of action and renal penetration, provide fresh hope for improving renal health and quality of life in patients with kidney disease. The current study highlights therapeutic ability, stability, nephroprotection, and toxicity profiles, as well as the importance of continuous research in this dynamic and evolving field.

Aim: Chemotherapy has been well shown to enhance life expectancy in patients with malignancy. However, conventional chemotherapy drugs, particularly cisplatin, are highly associated with nephrotoxicity, which limits therapeutic efficacy and impairs quality of life. Histone deacetylases (HDACs) are proteases that play significant roles in diseases by influencing protein post-translational modification and gene expression. Agents that inhibit HDAC enzymes have been developed and approved by the FDA as anticancer drugs. It is worth noting that in certain preclinical studies with tumour cell lines, the integration of HDAC modulators and cisplatin not only exerts synergistic or additive tumour-killing effects but also alleviates cisplatin nephrotoxicity. The aim of this review is to discuss the role of HDACs in cisplatin nephrotoxicity.

Methods: After searching in PubMed and Web of Science databases using 'Histone deacetylase', 'nephrotoxicity', 'cisplatin', and 'onconpehrology' as keywords, studies related was compiled and examined.

Results: HDAC inhibitors exert renal protective effects by inhibiting inflammation, apoptosis, oxidative stress, and promoting autophagy; whereas sirtuins play a renal protective role by regulating lipid metabolism, inhibiting inflammation and apoptosis, and protecting mitochondrial biosynthesis and mitochondrial dynamics. These potential interactions provide clues concerning targets for molecular treatment.

Conclusion: This review encapsulates the function and molecular mechanisms of HDACs in cisplatin nephrotoxicity, providing the current view by which HDACs induce different biological signaling in the regulation of chemotherapy-associated renal injury. More importantly, this review exhaustively elucidates that HDACs could be targeted to develop a new therapeutic strategy in treating cisplatin nephrotoxicity, which will extend the knowledge of the biological impact and clinical implications of HDACs.

High-fructose corn syrup (HFCS) has been a subject of intense debate due to its association with cardiovascular risks. This study investigates the potential protective effects of selenium (Se) supplementation against cardiac damage induced by HFCS. Thirty-two male Wistar albino rats were divided into four equal groups: control, CS (20%-HFCS), CS with Se (20%-HFCS, 0.3 mg/kg-Se), and Se (0.3 mg/kg-Se) only. After a 6-week period, heart and aorta tissues were collected for histopathological, immunohistochemical, biochemical, and genetic analyses. HFCS consumption led to severe cardiac pathologies, increased oxidative stress, and altered gene expressions associated with inflammation, apoptosis, and antioxidant defenses. In the CS group, pronounced oxidative stress within the cardiac tissue was concomitant with elevated Bcl-2-associated X protein (Bax) expression and diminished expressions of B-cell-lymphoma-2 (Bcl-2), nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α), and silenced information regulator 1 (SIRT1). Se supplementation mitigated these effects, showing protective properties. Immunohistochemical analysis supported these findings, demonstrating decreased expressions of caspase-3, tumor necrosis factor-alpha (TNF-α), IL-1β, and vascular endothelial growth factor (VEGF) in the CS + Se group compared to the CS group. The study suggests that Se supplementation exerts anti-inflammatory, antioxidant, and antiapoptotic effects, potentially attenuating HFCS-induced cardiovascular toxicity. These findings highlight the importance of dietary considerations and selenium supplementation in mitigating cardiovascular risks associated with HFCS consumption.

Methotrexate (MTX) is widely prescribed to treat different malignancies as well as autoimmune diseases. However, it causes a range of side effects in different organs such as testis. This study aims to clarify the role of dipeptidyl peptidase 4 (DPP4) in MTX-induced testicular damage via pathways involved in oxidative stress and evaluates the protective effects of sitagliptin as a DPP4 inhibitor. Twenty-four animals randomly allocated into four groups including: (I) control, (II) MTX (20 mg/kg, i.p.), (III) sitagliptin (20 mg/kg, i.p., for four consecutive days), and MTX + sitagliptin in which received chemicals resembling group II and III. Histopathological examinations conducted to assess the structural changes in testes of different experimental groups. Also, ELISA method employed to investigate the levels of DPP4, AKT, p-AKT, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). In addition, the total malondialdehyde (MDA) content and the activity of superoxide dismutase (SOD) were assessed. The results indicated that MTX administration was accompanied with testicular damage, which reversed by sitagliptin treatment. The biochemical observations demonstrated that MTX markedly increased the levels of DPP4, decreased p-AKT/AKT ratio followed by a marked decrement in Nrf2 and HO-1 levels. Also, it was observed that MTX decreased the activity of SOD and increased total MDA content in testicular specimen. However, sitagliptin treatment diminished mentioned alterations effectively. Altogether, our findings supported the possible role of DPP4 in MTX-induced testicular toxicity along with the potential protective features of sitagliptin via suppressing of the histopathological and biochemical alterations induced by MTX.

Redox regulation is a fundamental physiological phenomenon related to oxygen-dependent metabolism, and skeletal muscle is mainly regarded as a primary site for oxidative phosphorylation. Several studies have revealed the importance of reactive oxygen and nitrogen species (RONS) in the signaling process relating to muscle adaptation during exercise. To date, improving knowledge of redox signaling in modulating exercise adaptation has been the subject of comprehensive work and scientific inquiry. The primary aim of this review is to elucidate the molecular and biochemical pathways aligned to RONS as activators of skeletal muscle adaptation and to further identify the interconnecting mechanisms controlling redox balance. We also discuss the RONS-mediated pathways during the muscle adaptive process, including mitochondrial biogenesis, muscle remodeling, vascular angiogenesis, neuron regeneration, and the role of exogenous antioxidants.

Esophageal cancer (ESC) is a malignant tumor that originates from the mucosal epithelium of the esophagus and is part of the digestive tract. Although the exact pathogenesis of ESC has not been fully elucidated, excessive oxidative stress is an important characteristic that leads to the development of many cancers. Abnormal expression of several proteins and transcription factors contributes to oxidative stress in ESCs, which alters the growth and proliferation of ESCs and promotes their metastasis. Natural compounds, including alkaloids, terpenes, polyphenols, and xanthine compounds, can inhibit reactive oxygen species production in ESCs. These compounds reduce oxidative stress levels and subsequently inhibit the occurrence and progression of ESC through the regulation of targets and pathways such as the cytokine interleukins 6 and 10, superoxide dismutase, the NF-+ACY-kappa+ADs-B/MAPK pathway, and the mammalian Nrf2/ARE target pathway. Thus, targeting tumor oxidative stress has become a key focus in anti-ESC therapy. This review discusses the potential of Natural products (NPs) for treating ESCs and summarizes the application prospects of oxidative stress as a new target for ESC treatment. The findings of this review provide a reference for drug development targeting ESCs. Nonetheless, further high-quality studies will be necessary to determine the clinical efficacy of these various NPs.

Rheumatoid arthritis (RA) is a chronic inflammatory condition known for its irreversible destructive impact on the joints. Chondrocytes play a pivotal role in the production and maintenance of the cartilage matrix. However, the presence of inflammatory cytokines can hinder chondrocyte proliferation and promote apoptosis. Isoliquiritigenin (ISL), a flavonoid, potentially exerts protective effects against various inflammatory diseases. However, its specific role in regulating the nuclear factor E2-associated factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in chondrocytes in RA remains unclear. To investigate this, this study used human chondrocytes and Sprague-Dawley rats to construct in vitro and in vivo RA models, respectively. The study findings reveal that cytokines markedly induced oxidative stress, the activation of matrix metalloproteinases, and apoptosis both in vitro and in vivo. Notably, ISL treatment significantly mitigated these effects. Moreover, Nrf2 or HO-1 inhibitors reversed the protective effects of ISL, attenuated the expression of Nrf2/HO-1 and peroxisome proliferator-activated receptor gamma-coactivator-1α, and promoted chondrocyte apoptosis. This finding indicates that ISL primarily targets the Nrf2/HO-1 pathway in RA chondrocytes. Moreover, ISL treatment led to improved behavior scores, reduced paw thickness, and mitigated joint damage as well as ameliorated oxidative stress in skeletal muscles in an RA rat model. In conclusion, this study highlights the pivotal role of the Nrf2/HO-1 pathway in the protective effects of ISL and demonstrates the potential of ISL as a treatment option for RA.

Accumulating data confirms that Methotrexate (MTX), a well-known immunosuppressive and anticancer drug, causes nephrotoxicity. Infliximab (INF), the inhibitor of tumor necrosis factor-alpha (TNF-α), was proven to have anti-inflammatory properties. Thus, it may have potential in preventing MTX-induced nephrotoxicity. Therefore, this study aimed to inspect the prospective nephroprotective effect of INF on MTX-induced rat nephrotoxicity through investigating the possible molecular mechanisms, including its interference with different death routes, oxidative stress as well as mitochondrial biogenesis. Rats received an INF intraperitoneal single dose of 7 mg/kg 72 h prior to a single 20 mg/kg MTX injection. MTX nephrotoxicity was demonstrated by significantly increased serum levels of the renal indicators urea and creatinine as well as renal inflammatory markers TNF-α and Interleukin-6 (IL-6) and the renal oxidative stress marker malondialdehyde (MDA), while renal antioxidant enzyme superoxide dismutase (SOD) was significantly decreased compared to control. INF injection prior to MTX markedly reversed these MTX-induced effects. Besides, MTX impaired mitochondrial biogenesis, while INF attenuated this impairment, as indicated by increased expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). Finally, MTX triggered apoptotic and autophagic cascades in renal tissues as evidenced by reduced anti-apoptotic Bcl-2 protein expression as well as elevated expression of the pro-apoptotic protein Bax and both key regulators of autophagy; beclin-1 and LC-3, whereas INF pretreatment counteracted these apoptotic and autophagic effects of MTX. Summarily, these results suggest that INF provides protection against MTX-induced nephrotoxicity which could be elucidated by its antioxidant, anti-inflammatory, anti-apoptotic and anti-autophagic effects as well as upregulating mitochondrial biogenesis.

Cisplatin, a potent chemotherapeutic agent, is marred by severe nephrotoxicity that is governed by mechanisms involving oxidative stress, inflammation, and apoptosis pathways. The transcription factor Nrf2, pivotal in cellular defense against oxidative stress and inflammation, is the master regulator of the antioxidant response, upregulating antioxidants and cytoprotective genes under oxidative stress. This review discusses the mechanisms underlying chemotherapy-induced kidney injury, focusing on the role of Nrf2 in cancer therapy and its redox regulation in cisplatin-induced kidney injury. We also explore Nrf2's signaling pathways, post-translational modifications, and its involvement in autophagy, as well as examine redox-based strategies for modulating Nrf2 in cisplatin-induced kidney injury while considering the limitations and potential off-target effects of Nrf2 modulation. Understanding the redox regulation of Nrf2 in cisplatin-induced kidney injury holds significant promise for developing novel therapeutic interventions. This knowledge could provide valuable insights into potential strategies for mitigating the nephrotoxicity associated with cisplatin, ultimately enhancing the safety and efficacy of cancer treatment.