Acetaminophen (APAP) is one of the most commonly used analgesic and antipyretic medications and is generally considered safe at therapeutic doses. However, overdose remains a leading cause of acute liver failure, primarily characterized by centrilobular (zone 3) hepatic necrosis, oxidative stress, mitochondrial dysfunction, and sterile inflammation. The hepatotoxic effects of APAP are localized to the centrilobular region, where cytochrome P450 2E1 is highly expressed. Cytochrome P450 2E1 catalyzes the conversion of APAP to a toxic metabolite, N-acetyl-p-benzoquinone imine. During overdose, the liver’s detoxification capacity is overwhelmed and excess N-acetyl-p-benzoquinone imine binds to cellular proteins, initiating oxidative stress and mitochondrial injury that culminate in hepatocyte death. A central component of APAP-induced hepatotoxicity is the activation of innate immune responses, particularly via inflammasome pathways. Inflammasomes are cytosolic multiprotein complexes that detect cellular damage and trigger inflammation. Among these, the NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome plays a significant role in APAP-induced liver injury. Upon activation, the NLRP3 inflammasome promotes autocatalytic cleavage of procaspase-1 into its active form, caspase-1, which subsequently processes the pro-inflammatory cytokines pro-interleukin-1β and pro-interleukin-18 into their mature forms. These cytokines recruit additional immune cells and amplify liver inflammation, exacerbating tissue injury. Thus, the NLRP3 inflammasome serves as a key mechanistic link between the initial toxic insult and the ensuing inflammatory response in APAP hepatotoxicity. This review aimed to explore the molecular mechanisms underlying APAP-induced liver injury, particularly inflammasome activation, and evaluate the current and emerging therapeutic strategies.

Liver fibrosis is a key process in the progression of chronic liver diseases. However, there are currently no drugs specifically designed to treat liver fibrosis. Our Phase 2 trial of hydronidone for the treatment of chronic hepatitis B (CHB)-associated liver fibrosis showed that adding hydronidone to entecavir resulted in significant reversal of liver fibrosis. To further evaluate the efficacy of a 270 mg/day dose of hydronidone for treating liver fibrosis associated with CHB, we conducted this Phase 3 trial.

This is a 52-week, randomized (1:1), double-blind, placebo-controlled, multicenter, entecavir-based Phase 3 clinical study conducted at 44 study centers across China. Adult patients aged 18 to 65 years with significant liver fibrosis (defined as an Ishak score ≥ 3 on liver biopsy) associated with CHB were included.

The primary endpoint of the trial is to demonstrate the efficacy of fibrosis reversal, defined as a decrease in the Ishak stage score of liver fibrosis by ≥1 after 52 weeks of treatment, compared to baseline.

The results of this trial are expected to further support the antifibrotic indication for this novel drug.

Poor bioavailability and a short half-life limit the therapeutic efficacy of ibuprofen. This study developed floating nanoballoons to enhance ibuprofen’s bioavailability and sustain its anti-inflammatory effects through improved gastric retention.

Ibuprofen-loaded nanoballoons were synthesized using solvent evaporation with ethyl cellulose as the polymer matrix. The formulation was characterized for morphology, buoyancy, drug loading, and release kinetics. In vivo studies assessed the anti-inflammatory efficacy in acute and chronic inflammation models using male Sprague-Dawley rats.

The nanoballoons exhibited optimal characteristics, including 96% buoyancy and a drug loading efficiency of 96.54 ± 1.32%. Scanning Electron Microscopy revealed a spherical morphology with a porous structure. Drug release followed a biphasic pattern: an initial release of 35.23 ± 2.13% over 2 h, followed by sustained release reaching 97.54 ± 1.30% at 12 h. In acute inflammation studies, the nanoballoon formulation showed superior edema inhibition (68.12%) compared to pure ibuprofen (51.67%). Chronic inflammation studies demonstrated significant improvements in inflammatory markers: reduced TNF-α (19.12 ± 0.48 vs. 31.11 ± 1.23 pg/mL), hs-CRP (201.7 ± 11.02 vs. 232.12 ± 11.33 ng/mL), and IL-6 (100.01 ± 18.40 vs. 135 ± 11.22 pg/mL), with increased anti-inflammatory IL-10 (507.18 ± 10.11 vs. 276.11 ± 19.16 pg/mL).

The developed floating nanoballoon system significantly enhanced ibuprofen’s bioavailability and anti-inflammatory efficacy, presenting a promising gastro-retentive delivery platform for poorly water-soluble drugs.

Propolis is a resinous material produced by honeybees. Its chemical composition is highly complex and varies significantly depending on geographic region and season. This intrinsic variability presents challenges to the standardization and quality control of propolis. This study aimed to evaluate the chemical composition, total phenolic content, and antioxidant potential of propolis collected from seventeen geographical regions across Africa.

A reverse-phase high-performance liquid chromatography (RP-HPLC) method coupled with a photodiode array detector (PDA) was used for analysis of propolis samples. The flavonoid and phenolic contents of the samples were determined using colorimetric and Folin-Ciocalteu methods. Antioxidant capacity was assessed using the 2,2-diphenyl-1-picrylhydrazyl assay.

Five flavonoids (naringenin, pinocembrin, galangin, chrysin, and quercetin), one flavonoid glycoside (rutin), six phenolic acids (caffeic acid, p-coumaric acid, cinnamic acid, chlorogenic acid, ferulic acid, and gallic acid), and an aromatic ester - caffeic acid phenethyl ester were simultaneously detected and quantified using RP-HPLC with an ACE-5 C18 column (250 mm × 4.6 mm i.d., 5 µm) and PDA detector. The reference standards showed good linearity with regression coefficients (R2) ranging from 0.96 to 0.99. For precision, repeatability, and stability studies, the relative standard deviation for all reference standards was below 2.5%. The 2,2-diphenyl-1-picrylhydrazyl assay yielded EC50 values ranging from 17.6 ± 0.39 to 0.16 ± 0.001 mg/mL.

RP-HPLC method for the simultaneous quantification of thirteen reference standards will serve as a reliable tool for the standardization and quality evaluation of propolis. The flavonoid and phenolic contents are key contributors to the antioxidant activity of propolis and reflect local plant biodiversity and bee–plant interactions within the ecosystem.

Philadelphia chromosome-positive (Ph+) B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) is an aggressive hematologic malignancy driven by the BCR::ABL1 fusion. While many cases respond well to treatment, some patients exhibit persistent BCR::ABL1 expression after therapy, presenting significant diagnostic challenges.

We present the case of a seven-year-old girl diagnosed with Ph+ B-ALL. Despite low percentages or negative results for blasts post-treatment, molecular and cytogenetic studies persistently detected high levels of BCR::ABL1, suggesting a high disease burden at the genetic level. This discordance supported multilineage involvement and the potential for retrospective revision of the initial diagnosis to lymphoblast crisis of chronic myeloid leukemia (LBC-CML).

Classifying such cases as de novo Ph+ B-ALL with multilineage involvement or LBC-CML is challenging, as there is currently no consensus among experts. Further studies are necessary to clarify the distinction, given the different management strategies and treatment responses between these two conditions.

Metabolic dysfunction-associated steatotic liver disease (MASLD), the most common chronic liver disorder worldwide, results from multidimensional network dysregulation involving lipid metabolism imbalance, insulin resistance, oxidative stress, chronic inflammation, and gut-liver axis disruption. Silent information regulator 1 (SIRT1), an NAD+-dependent deacetylase, functions as a central regulator of metabolic homeostasis and a key mediator in immune microenvironment remodeling and inter-organ communication. This review systematically describes the multi-target mechanisms of SIRT1 in MASLD pathogenesis through its regulation of critical factors, including peroxisome proliferator-activated receptor gamma coactivator 1-α, Forkhead Box O, and nuclear factor kappa-light-chain-enhancer of activated B cells, which govern hepatocyte lipid remodeling, mitochondrial quality control, autophagy–endoplasmic reticulum stress balance, and Kupffer cell/T cell polarization. This work introduces, for the first time, the concept that SIRT1 mediates systemic regulation of MASLD via coordinated “metabolism–inflammation–organ axis” interactions. Recent studies indicate that natural compounds (e.g., resveratrol, curcumin) improve gut-liver barrier function through microbiota–SIRT1 interactions, while synthetic activators (SRT1720) and NAD+ precursors (NMN) enhance hepatocyte antioxidant capacity and fatty acid β-oxidation. This innovative analysis highlights the spatiotemporal specificity of various SIRT1 activators, emphasizing that tissue-selective delivery and dynamic dosage optimization are crucial for overcoming clinical translation challenges. By integrating mechanistic and translational insights, this review provides a novel foundation for precision intervention strategies targeting SIRT1 network reprogramming.

Immunization against human papillomavirus (HPV), particularly with a single-dose vaccine, offers a cost-effective strategy for cervical cancer prevention. This study aimed to evaluate the seroprevalence following a single-dose bivalent HPV vaccine among adolescent girls in Bangladesh and to examine its association with sociodemographic characteristics.

A cross-sectional study was conducted among 648 adolescent girls (aged nine to fifteen years) in Dhaka, Bangladesh, who received a single dose of the bivalent HPV vaccine in November 2019. Participants were recruited from ten local schools. At 36 months post-vaccination, blood samples were analyzed for HPV16/18 L1-specific immunoglobulin G using enzyme-linked immunosorbent assay. Sociodemographic data were collected and analyzed using logistic regression.

Most participants were aged nine to thirteen years (82.4%), with a mean age of 11.89 ± 1.59 years. The overall seroprevalence was 72.8% for HPV16 and 82.4% for HPV18. Seropositivity for HPV16 was significantly lower among participants aged 14–15 years [adjusted odds ratio (aOR) = 0.61; 95% confidence interval (CI): 0.39–0.95; p = 0.020] and those in grades nine to ten (aOR = 0.50; 95% CI: 0.28–0.89; p = 0.004). For HPV18, significantly reduced odds of seropositivity were observed among participants from households with monthly incomes up to Taka 10,000 (aOR for Taka 10,001–20,000 = 0.41; 95% CI: 0.26–0.67; p < 0.001; aOR for Taka 20,001–50,000 = 0.21; 95% CI: 0.11–0.40; p < 0.001).

A single-dose bivalent HPV vaccine induces sustained immunity in Bangladeshi adolescent girls, with lower HPV16 seropositivity among older girls and those in higher grades, and higher HPV18 seropositivity is linked to lower household income.

Leishmaniasis is a systemic parasitic disease that can affect unusual sites such as the lungs.

We report a case of a 45-year-old male with human immunodeficiency virus infection who presented with abdominal pain and vomiting. Imaging studies revealed minimal bilateral ground-glass opacities in the lungs, hepatosplenomegaly, and diffuse lymphadenopathy. A bronchoscopy with bronchoalveolar lavage cytology evaluation showed abundant macrophages containing numerous intracellular organisms with characteristic dot-like kinetoplasts, confirming the diagnosis of Leishmaniasis. Special stains for other infections were negative.

This case highlights the value of bronchoalveolar lavage cytology in diagnosing non-neoplastic lung pathologies, including parasitic infections like Leishmaniasis, thereby enabling prompt and targeted treatment.

Patients with acute liver failure (ALF) or acute-on-chronic liver failure (ACLF) are at high risk of bleeding with traditional artificial liver support systems. To address the bleeding risk in liver failure patients, the safety of regional mesylate anticoagulation (RMA) in centrifugation artificial liver support systems (cALSS) is proposed for study.

In this prospective single-arm study, ALF and ACLF patients were treated with cALSS using RMA. Coagulation function was monitored, and the predictors of mesylate dose were analyzed using the area under the curve (AUC). Blood ammonia, model for end-stage liver disease scores, and survival rates at 28 and 90 days were assessed.

All 57 patients showed no new bleeding within 24 h post-cALSS. Most disseminated intravascular coagulation indicators improved at 0.5 h and 24 h post-cALSS. Thromboelastography showed hypocoagulability at 0.5 h post-cALSS. Univariate and multivariate analyses identified pre-R and pre-MA as key factors for R exceeding 10 m at 0.5 h post-cALSS, with odds ratios of 0.91 (95% confidence interval (CI): 0.84–0.98) and 2.03 (95% CI: 1.05–3.90), respectively, P < 0.05. The predictive values were pre-MA ≤ 38 mm (AUC = 0.817, 95% CI [0.690–0.907], P < 0.001) and pre-R > 6.3 m (AUC = 0.790, 95% CI [0.661–0.888], P < 0.001). Patients showed improvements in blood ammonia and model for end-stage liver disease scores after the last session, especially those with high initial levels (>80 µmol/L and >30). The 28-day and 90-day survival rates of ALF patients were similar to those of ACLF patients.

cALSS with RMA is safe for liver failure patients with a high risk of bleeding. Adjusting the mesylate dose based on pre-R and pre-MA enhances safety.

This study investigates the potential of methyl eugenol (ME), a compound found in the essential oils of various plants, to inhibit oxidative stress and its impact on diseases associated with this process. ME has been shown to possess antioxidant properties and antiproliferative activity in several cancers. It also demonstrates neuroprotective potential in conditions such as Alzheimer’s disease and ischemic brain injury. The mechanism of action involves the activation of the nuclear factor erythroid 2-related factor 2, which facilitates the transcription of antioxidant genes and modulation of pathways such as AMP-activated protein kinase/glycogen synthase kinase 3 beta, thereby reducing the production of reactive oxygen species and pro-inflammatory cytokines. However, research has identified potential toxicological risks associated with ME, including hepatotoxicity and changes in the gut microbiota. These findings highlight the need for caution when considering prolonged exposure to this compound.