Nobiletin (NOB) is a flavonoid derived from citrus peel that has potential as an alternative treatment for liver disease. Liver disease is a primary health concern globally, and there is an urgent need for effective drugs. This review summarizes the pharmacological characteristics of NOB and current in vitro and in vivo studies investigating the preventive and therapeutic effects of NOB on liver diseases and its potential mechanisms. The findings suggest that NOB has promising therapeutic potential in liver diseases. It improves liver function, reduces inflammation and oxidative stress, remodels gut microflora, ameliorates hepatocellular necrosis, steatosis, and insulin resistance, and modulates biorhythms. Nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear transcription factor kappa (NF-κB), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor α(PPAR-α), extracellular signal-regulated kinase (ERK), protein kinase B (AKT), toll-like receptor 4 (TLR4) and transcription factor EB (TFEB) signaling pathways are important molecular targets for NOB to ameliorate liver diseases. In conclusion, NOB may be a promising drug candidate for treating liver disease and can accelerate its application from the laboratory to the clinic. However, more high-quality clinical trials are required to validate its efficacy and identify its molecular mechanisms and targets.
11 January 2021 in Experimental and Therapeutic Medicine
Mycoplasma is one of the most common pathogens causing community‑acquired pneumonia in pediatric patients. In recent years, the number of refractory or severe cases with drug resistance has been gradually increasing and cases that developed embolism after Mycoplasma pneumoniae (M. pneumoniae) infection have been reported. The present study retrospectively analyzed the clinical features, diagnosis and treatment of M. pneumoniae pneumonia (MPP) combined with pulmonary embolism (PE) in a series of 7 cases encountered between January 1st, 2016 to August 1st, 2019 at the Department of Pediatric Intensive Care Unit of The First Hospital of Jilin University (Changchun, China). Combined with relevant Chinese and international studies published during the last two decades, a comprehensive analysis was performed. All of the pediatric patients of the present study had fever, cough and dyspnea respiratory symptoms at onset and the disease progressed rapidly. Thereafter, PE was confirmed by a series of examinations. Pulmonary CT indicated patchy inflammations and significantly elevated D‑dimer levels, accompanied by positive anticardiolipin antibodies. Furthermore, a filling defect in the pulmonary artery branch was observed on CT pulmonary angiography (CTPA) examination. In 2 cases, the condition was improved with anti‑infection and anticoagulation treatment with low‑molecular‑weight heparin and warfarin, respectively, and the pulmonary embolism disappeared after 3‑4 months. A total of 5 cases, who were not responsive to the drug treatment, underwent surgical resection. During the operation, the local tissues were determined to be infarcted and the pathological diagnosis was consistent with pulmonary infarction. Among the 5 cases, 2 died of Acute Respiratory Distress Syndrome at 3‑8 days after the operation. The remaining patients underwent 6‑12 months of follow‑up and respiratory rehabilitation and their quality of life is now good. In conclusion, compared with healthy individuals, pediatric patients with critical MPP have an elevated risk of embolism. It is necessary to be vigilant regarding whether MMP is combined with PE and perform timely CTPA examination. Early detection, early treatment and surgical intervention (if necessary) may significantly reduce the risk of mortality and disability.
7 July 2021 in Experimental and Therapeutic Medicine
Mycoplasma pneumoniae is a common pathogen causing respiratory infections in children and adults. In addition to respiratory diseases, Mycoplasma pneumoniae is also involved in numerous extrapulmonary diseases. Thrombosis is an extrapulmonary manifestation associated with Mycoplasma pneumoniae infection. In recent years, an increasing number of case reports have been published identifying thrombosis secondary to Mycoplasma pneumoniae infection. In the present study, the available relevant literature in English available on PubMed, Medline and Web of Science was consulted. The results of the present study demonstrated that in patients with thrombosis caused by Mycoplasma pneumoniae infection, some of the factors causing thrombosis are transient and some are due to hereditary thrombophilia. Following timely treatment, the majority of patients recovered completely but some patients had a poor prognosis. The present review focuses on the pathogenesis, clinical features, treatment and prognosis of this crucial issue, which contributes toward the understanding of the disease.
Pediatric acute liver failure (PALF) due to mushroom poisoning is a rare and life-threatening disease. There is no specific treatment. Plasma exchange (PE) is often used as a bridge to the regeneration of the liver or transplantation. However, PE is limited due to an inadequate plasma supply and transfusion-related risks. The double plasma molecular adsorption system (DPMAS) can adsorb toxins, including bilirubin and inflammatory mediators. However, the DPMAS cannot improve coagulation disorders. Combining PE and the DPMAS could compensate for the shortcomings of the two techniques. A previous study showed that the combination might be more effective than using PE or the DPMAS alone in patients with mild acute-on-chronic liver failure. To the best of our knowledge, few studies combined PE and the DPMAS for the treatment of PALF due to mushroom poisoning. Here, we specifically describe our experience with PE and the DPMAS in PALF. In conclusion, our study shows that the DPMAS and PE are safe and effective in reducing the bilirubin level and improving blood coagulation in PALF due to mushroom poisoning as a bridge to transplantation or recovery.
Burgeoning is an evolution from conventional photodynamic therapy (PDT). Thus, sonodynamic therapy (SDT) regulated by nanoparticles (NPs) possesses multiple advantages, including stronger penetration ability, better biological safety, and not reactive oxygen species (ROS)-dependent tumor-killing effect. However, the limitation to tumor inhibition instead of shrinkage and the incapability of eliminating metastatic tumors hinder the clinical potential for SDT. Fortunately, immune checkpoint blockade (ICB) can revive immunological function and induce a long-term immune memory against tumor rechallenges. Hence, synergizing NPs-based SDT with ICB can provide a promising therapeutic outcome for solid tumors. Herein, we briefly reviewed the progress in NPs-based SDT and ICB therapy. We highlighted the synergistic anti-tumor mechanisms and summarized the representative preclinical trials on SDT-assisted immunotherapy. Compared to other reviews, we provided comprehensive and unique perspectives on the innovative sonosensitizers in each trial. Moreover, we also discussed the current challenges and future corresponding solutions.
28 October 2025 in Trends in Pharmacological Sciences
Bromodomain-containing protein 4 (BRD4) is a key transcriptional regulator in the bromodomain and extraterminal (BET) family. It promotes cancer and inflammation by binding to chromatin through its bromodomains. Although bromodomain inhibitors (e.g., BETi) show preclinical efficacy, their clinical application has been limited primarily by dose-limiting toxicities (DLTs), with resistance emerging as a secondary challenge. This motivates the development of strategies beyond conventional bromodomain inhibition. Here, we review emerging evidence that BRD4 sustains oncogenic programs through bromodomain-independent mechanisms, and discuss innovative approaches designed to overcome DLT. These include BRD4-targeted degraders, nonbromodomain ligands that disrupt scaffolding functions, post-translational modification (PTM) disruptors, and condensate modulators. We also discuss advances in chemically induced proximity (CIP) platforms that enable disease-state transcriptional reprogramming, and rational combination therapies (e.g., epigenetic-kinase inhibitors and BETi-immunotherapy integration) that minimize toxicity while addressing emerging resistance. Together, these approaches open new therapeutic frontiers for treating BRD4-driven diseases.