The molecular target and detailed mechanism of analgesic acetaminophen are still not fully understood despite being commonly used for many years. Through a literature search, the present study aimed to characterize the cyclooxygenase inhibitory properties of acetaminophen in comparison with non-steroidal anti-inflammatory drugs and to gain novel mechanistic insights into its analgesic action, especially focusing on the peripheral mechanisms. Comparative characterization indicated that acetaminophen is relatively selective for cyclooxygenase-2 but less potent to inhibit cyclooxygenase than non-steroidal anti-inflammatory drugs. This narrative review suggests that acetaminophen is very likely to be a prodrug, which is metabolically converted into bioactive N-arachidonoylphenolamine, AM404, by fatty acid amide hydrolase-mediated conjugation of acetaminophen metabolite 4-aminophenol with arachidonic acid not only in the central nervous system but also in the peripheral nervous system. It is considered that AM404 activates transient receptor potential vanilloid 1 and cannabinoid type 1 receptor distributed in the brain and spinal cord to induce analgesia centrally. In addition, it is speculated that AM404 produced in trigeminal ganglion neurons, dorsal root ganglion neurons, and primary sensory neurons inhibits nociceptive voltage-gated sodium channels through the local anesthetic binding site to suppress pain signaling and inhibits cyclooxygenase-2 to prevent the biosynthesis of prostaglandins responsible for nociception, thereby inducing peripheral analgesia. We propose the mechanistic hypothesis for the analgesic effects of acetaminophen to integrate central and peripheral action of its bioactive entity AM404, which should provide the pharmacological rationale for the use of acetaminophen to relieve postoperative and inflammatory pain and its application to multimodal analgesia.

Carbohydrate restriction has been proposed as an adjunctive strategy in cancer, largely because many tumours show high glucose uptake. Clinical evidence for benefit remains limited, mixed and often overstated. Lactate is now recognised as more than a metabolic by-product: it influences redox balance, tumour-stromal signalling, immune suppression, angiogenesis, epigenetic regulation and metastatic behaviour. This Review considers carbohydrate-restrictive diets from a lactate-centred perspective. The stronger mechanistic argument is not simple glucose deprivation, but the possibility that lower carbohydrate availability may reduce glucose-to-lactate flux and disrupt lactate-dependent tumour ecosystems in selected contexts. It discusses where this idea is biologically plausible, where claims run beyond the data, and how dietary approaches compare with direct lactate-targeted strategies. To ground the clinical discussion, registered interventional trials of caloric and/or carbohydrate manipulation in cancer were reviewed; they show an active but early-stage field dominated by small, heterogeneous studies and few direct lactate-related endpoints. Future trials should use biomarker-guided tumour selection, direct measures of tumour lactate flux, immune and microenvironmental endpoints, and explicit safeguards for weight, muscle mass, treatment tolerance and quality of life. At present, carbohydrate restriction should remain investigational and be tested only in well-designed clinical studies with clear nutritional safeguards.

Postpartum thyroiditis (PPT) is a common autoimmune sequela of pregnancy, affecting 5-10% of women, a considerable percentage of whom ultimately develop lifelong hypothyroidism. The disorder's characteristic symptoms, such as debilitating tiredness and cognitive impairment, are frequently misattributed to the routine challenges of new parenthood, leading to delayed diagnosis and adverse effects on maternal quality of life and newborn development. Evidence suggests that the currently utilized reactive, clinic-based model of care may be insufficient to address this significant and often overlooked public health concern.The fundamental paradigm change toward a proactive, community-based treatment strategy to secure long-term maternal thyroid health. We synthesize available evidence on PPT pathophysiology, including the post-delivery immunological rebound, and examine the potential role of diet and micronutrient supervision in both primary and secondary prevention. We detail the function of essential micronutrients, including the delicate balance of iodine, the antioxidant protection provided by selenium, and the necessity of iron for thyroid hormone production. Available data suggest that while high iodine consumption is a modifiable risk factor, dietary shortages in these and other key nutrients may significantly exacerbate thyroid dysfunction.This review outlines a comprehensive Community-Based Care (CBC) framework that transcends conventional clinical settings, advocating for the integration of telehealth with trained community health professionals to provide systematic screening, education, and professional dietary oversight. By prioritizing the identification of at-risk women and implementing consistent, personalized nutritional management, this methodology offers a robust approach to proactive prevention, thereby reducing the significant long-term burden of PPT and improving maternal health outcomes.