Search Results (44)

Background: Pertussis, diphtheria, tetanus, poliomyelitis, and Haemophilus influenzae type b (Hib) infections pose severe threats to children’s health globally. This study evaluated the safety and immunogenicity of a novel Sabin strain-based adsorbed pentavalent vaccine (DTacP-sIPV/Hib), which offers potential advantages in biosafety and cost-effectiveness compared to wild-type poliovirus-based vaccines. Methods: A repeated-dose toxicity study was conducted in 190 Sprague-Dawley rats, randomly divided into negative control, adjuvant control, low-dose, and high-dose groups. Animals received five intramuscular injections at 21-day intervals, followed by a 56-day recovery period. Parameters assessed included local reactions, body temperature, hematology, serum biochemistry, coagulation, histopathology, T-cell subsets, cytokine levels, and antigen-specific immunogenicity. Results: The primary adverse reaction was dose-dependent local muscle swelling, which was fully reversible within 3–21 days. Only transient body temperature fluctuations and adjuvant-related hematological/biochemical abnormalities were observed, all resolving after the recovery period. No vaccine-related damage occurred in hepatic/renal function or immune organs. Immunogenicity data showed 100% seroconversion for all bacterial components 21 days after the first dose. The high-dose group achieved 100% seropositivity for all poliovirus serotypes after the second dose, while the low-dose group reached the same after the third dose, with no significant difference in antibody levels between dose groups. Conclusions: The DTacP-sIPV/Hib vaccine exhibits a favorable safety profile and robust immunogenicity in rats, supporting its further clinical development. The use of Sabin strains reduces biosafety risks and manufacturing costs, making this vaccine a promising candidate for immunization programs, especially in resource-limited regions. Full article

Steatotic liver disease (SLD) represents a major global health burden, with environmental toxicants emerging as critical contributors alongside metabolic dysfunction. Bisphenol F (BPF), an increasingly prevalent replacement for bisphenol A, is widely detected in human biological samples and environment, yet its hepatotoxic mechanisms remain incompletely characterized. This review synthesizes current evidence on BPF-induced SLD, with a particular focus on resolving the “pregnane X receptor (PXR) paradox”, the mismatch between BPF’s weak direct activation of PXR and the PXR-like metabolic effects observed in vivo. Comprehensive analysis of mechanistic pathways reveals that BPF-induced SLD develops predominantly through PXR-independent mechanisms involving oxidative stress, endoplasmic reticulum dysfunction, Drp1-mediated mitochondrial fission, NLRP3/NF-κB-driven inflammation, dysregulated post-translational modifications, and epigenetic remodelling. These converging pathways collectively disrupt hepatic lipid metabolism, promote triglyceride accumulation, and establish a self-perpetuating cycle of metabolic dysfunction. Notably, weak indirect PXR modulation via oxidative stress represents a secondary, non-causal mechanism unsupported by functional validation. This framework distinguishes toxicant-induced steatosis from metabolic dysfunction-associated steatotic liver disease while highlighting critical evidence gaps—particularly the absence of causal PXR validation studies and human epidemiological data. Therapeutic opportunities exist at validated convergence points including mitochondrial dynamics (Drp1), inflammatory signalling (NLRP3/NF-κB), and energy metabolism (AMPK-mTOR), though combination strategies targeting multiple pathways will likely be required for durable disease reversal. These findings necessitate the expansion of regulatory screening paradigms to incorporate cellular stress pathway biomarkers alongside traditional nuclear receptor endpoints, ensuring comprehensive hepatotoxic risk assessment of emerging BPA substitutes. Full article

Diabetes mellitus (DM) is a complex, heterogeneous, hyperglycemic chronic metabolic disorder. Type 2 diabetes mellitus (T2DM) is characterized by progressive loss of insulin secretion from pancreatic islet β-cells due to IR (insulin resistance), which is a feature of metabolic syndrome (MetS). Chronic hyperglycemia in patients with T2DM in synergy with other metabolic abnormalities causes complications such as diabetic ketoacidosis, osmotic diuresis and hyperglycemic diabetic coma, as well as chronic microvascular and macrovascular complications such as atherosclerotic cardiovascular disease (ASCVD), peripheral artery disease (PAD) and cerebrovascular events, which implicate the formation of reactive species and the promotion of inflammatory pathways. In these events, natural or synthetic antioxidants and minerals seem to have ameliorative effects and may serve as beneficial co-treatment options. In view of these terms, the aim of this study is to investigate the underlying mechanisms of T2DM, its clinical presentation, and its complications. Additionally, the association of the pathogenesis of T2DM and the occurrence of its complications with obesity, chronic inflammation, oxidative stress (OS), insulin resistance (IR), hepatic steatosis, and dyslipidemia is examined, whilst molecular pathways, such as NF-κB and JAK/STAT, are also summarized, under the scope of the effects of several antioxidant compounds and minerals on their progression. The interrelation of T2DM with these conditions, as well as the effects of antioxidant supplementation, seems to be bidirectional, and it is recommended that obese patients be screened for T2DM and adopt lifestyle changes, including exercise, diet modification, and weight loss, in addition to potentially taking multifunctional supplements that offer antioxidant and anti-inflammatory potential. However, many aspects of the protective mechanisms of such antioxidants remain to be elucidated, with more drawbacks in their pharmacokinetic behavior, such as their poor absorption and solubility, waiting to be resolved. Full article

Water alkalinization is a critical global stressor for freshwater fish, yet the systemic patterns of multi-organ responses and injury remain insufficiently understood. This study integrates histopathology, biochemistry, and multi-organ transcriptomics to provide an integrated, time-resolved assessment of stress responses in European perch (Perca fluviatilis) exposed to acute alkaline stress (20 mmol/L). The analysis indicated that alkaline stress initially causes structural disturbance of gill tissue (lamellar fusion, necrosis) within 96 h, associated with impaired osmoregulatory functions. This primary dysfunction was followed by progressive hepatic impairment, characterized by uncontrolled oxidative stress (elevated levels in Malondialdehyde, MDA) and widespread hepatocyte necrosis. Transcriptomic analysis identified extensive transcriptional shifts associated with these alterations: large-scale differential expression in the liver (3629 Differentially Expressed Genes, DEGs) and kidney (478 DEGs). Notably, the liver exhibited a stress-responsive transcriptional profile involving activation of the HIF-1 signaling pathway and mobilizing protein quality control systems (e.g., ‘Proteasome,’ ‘Lysosome’) consistent with mitigation of proteotoxic stress. This compensatory response appeared insufficient to prevent severe metabolic disruption and cellular injury. This study presents a time-associated sequence of organ-specific stress responses under acute alkalinity, identifying candidate stress-associated genes (slc7a11, egln3, klhl38b) as potential targets for future functional studies and breeding alkali-tolerant strains. Full article

Occult hepatitis B virus infection (OBI), characterized by extremely low viral loads and the persistent intrahepatic presence of cccDNA, poses a profound challenge to global public health security. With a prevalence ranging from 0.06% to over 15% in different donor populations, OBI maintains a risk of transmission and can progress to hepatocellular carcinoma. Its prevention and control have long been limited by the sensitivity constraints of conventional detection methods, highlighting the urgent need for more sensitive diagnostic innovations. Emerging technologies offer distinct breakthroughs: ddPCR facilitates absolute quantification; CRISPR-Cas systems coupled with isothermal amplification enable rapid, point-of-care testing; third-generation sequencing resolves viral integration and mutations; and nanomaterials enhance the signal detection. This review synthesises advancements in OBI diagnostic technologies and provides a comparative overview of their strengths, limitations, and transfusion safety implications, as well as their potential applications in blood transfusion. Recommendations are also proposed to inform the advancement of OBI risk control in blood transfusion and to guide the development of novel diagnostic technologies, particularly relevant to regions with high HBV endemicity, such as China. Full article

Background/Objectives: Serological and molecular screening for Hepatitis B virus (HBV) has been essential in reducing the risk of transfusion-transmitted infection, particularly in regions of high endemicity. This retrospective study aimed to analyze the epidemiological profile and laboratory outcomes of 259 blood donors deemed ineligible after initial reactive or inconclusive screening for HBV markers. Methods: Donors were summoned for revaluation at the HEMOPA Foundation, in Belém, Pará, between February 2015 and July 2016. Demographic data, risk factors, and results for HBsAg, anti-HBc, anti-HBs, and HBV DNA obtained at the donation and return time points were collected. Results: The mean age was 37 ± 11.25 years, with a predominance of males (56.8%) and first-time donors (76%). At the return time point, 63.7% presented a profile indicative of resolved HBV infection and 3.5% of active infection, 6.6% were susceptible to HBV infection, and 1.9% presented vaccine-induced HBV immunity. Cases of Occult Hepatitis B Infection (OBI, 0.4%) and Window Period (WP, 0.4%) were also identified. Conclusions: The findings reveal a high prevalence of resolved HBV infection among ineligible donors, particularly first-time donors, and reinforce the importance of combined serological and molecular screening, as well as the need for vaccination and health education strategies for at-risk populations. As a public blood bank located in the Amazon region, we highlight that local epidemiological specificities must be considered in the formulation of public health policies that are sensitive to the regional context. Full article

Background: Hepatitis B core-related antigen (HBcrAg), a novel serum biomarker reflecting the activity of intrahepatic covalently closed circular DNA (cccDNA), has generated conflicting evidence regarding its clinical utility for predicting post-antiviral therapy relapse in chronic hepatitis B (CHB) patients. Methods: We systematically analyzed 13 studies (15 cohorts, n = 1529 patients) from PubMed, Web of Science, Wanfang, and CNKI (through April 2025). A bivariate model evaluated HBcrAg’s predictive performance for relapse outcomes, including virological relapse, clinical relapse, and hepatitis flares. Results: HBcrAg demonstrated a pooled sensitivity of 0.81 (95% CI: 0.75–0.86) and specificity of 0.72 (95% CI: 0.67–0.76) for relapse prediction, with a diagnostic odds ratio of 10.66 (95% CI: 7.36–15.42) and summary AUC of 0.83 (95% CI: 0.80–0.86). Subgroup analysis identified threshold effects as the primary source of heterogeneity, which resolved (I² < 13%) after excluding studies with outlier cutoff values. Meta-regression established that HBcrAg’s predictive value was unaffected by age, sex, hepatitis B e antigen status, or detection methods (p > 0.05). Conclusions: HBcrAg is validated as a robust non-invasive biomarker to optimize treatment cessation strategies, with high sensitivity providing strong negative predictive value in CHB populations. Future research should prioritize multi-marker models to enhance prediction accuracy. Full article

Background/Objectives: Sustained drug exposure is a key factor in the treatment of patients infected with human immunodeficiency virus (HIV) or hepatitis B virus (HBV) in order to achieve the intended virological response. Although influenced also by other parameters, adherence to the treatment scheme is the most important for adequate drug exposure. This can be assessed by therapeutic drug monitoring (TDM). Tenofovir (TFV) is a nucleotide analogue used in the treatment of both HIV and HBV. Although various analytical methods for the quantification of tenofovir prodrugs have been published, there is limited literature on methods for simultaneous TFV and its active metabolite, tenofovir diphosphate (TFVDP) direct determination. Methods: In this study, we describe a novel micro-liquid-chromatography-mass spectrometry (micro-LC-MS/MS) method for TDM of TFV and TFVDP in biological matrices (whole blood, plasma). The challenging separation of the high-polarity analytes was resolved on an amino stationary phase, eluted in HILIC (hydrophilic interaction liquid chromatography) mode. The sample preparation included a clean-up step with hexane for the removal of lipophilic compounds and then protein precipitation with organic solvent. Results: The achieved low limits of quantification in blood were 0.25 ng/mL for TFV, and 0.5 ng/mL for TFVDP. Linearity, accuracy (91.63–109.18%), precision (2.48–14.08), and stability were validated for whole blood matrix, meeting the guidelines performance criteria. Samples collected from treated patients were analyzed, with results being in accordance with the reported pharmacokinetics. Conclusions: The new method is adequate for analyzing samples in a clinical set-up. The measurement of both TFV and TFVDP improves clinical decision by an in-depth evaluation of long-term adherence, and together with viral load and resistance data helps guiding the treatment towards the intended virological suppression. Full article

Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic, immune-mediated inflammatory disorder of the gastrointestinal tract. Immunosuppressive therapy administration increases the risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) reactivation. This study aimed to investigate the hepatitis screening rate, serological status, and protective antibody levels among the Taiwanese IBD population. This single-center retrospective study included patients with IBD from January 2016 to December 2024. Hepatitis serological markers were analyzed. Patients were categorized into active HBV infection (HBsAg-positive), resolved HBV infection (HBsAg-negative and anti-HBc-positive), and non-HBV-infected groups, with prevalences of 7.5%, 32.5%, and 0.9%, respectively. This study included 347 patients with IBD (UC: 68.3%; CD: 31.7%), with a mean age of 47.1 ± 16.4 years. Patients born after 1984 demonstrated a significantly reduced HBsAg positivity (0.9% vs. 11.0%; p < 0.05) and resolved HBV infection (52.2% vs. 1.0%; p < 0.05). However, among non-HBV-infected individuals, only 42.0% had protective anti-HBs levels (≥10 mIU/mL), despite vaccination program initiation. In this study, we found an overall HBsAg positivity rate of 7.5% and an anti-HCV seropositivity rate of 0.9% in our IBD population. Taiwan’s HBV vaccination program has effectively reduced the HBV prevalence. However, a significant proportion of vaccinated individuals lack sufficient protective antibody levels, thereby requiring continued HBV screening and booster vaccinations. Full article

Objectives: Chronic Hepatitis B virus (HBV) infection is a significant global health issue, with dialysis patients at increased risk and reduced response to HBV vaccination. The effects of HBV serological status on kidney transplant outcomes, particularly for patients with resolved or inactive HBV infection, needs more data, especially from current era. This study evaluated the impact of chronic and non-active HBV infection on patient and graft survival after kidney transplantation. Methods: Retrospective analysis was conducted of kidney-only transplant recipients at our center from 1 January 1990 to 31 August 2019 (end of observation). Patients were grouped by their HBV serostatus before transplantation into three categories: HBV negative (HBsAg−/Anti-Hbc−), non-active HBV infection (HbsAg−/Anti-Hbc+) and chronic HBV infection (HbsAg+/Anti-Hbc+). Primary outcomes included patient survival, graft survival, and overall graft and patient survival, analyzed using Kaplan–Meier (KM) curves, log-rank tests, Restricted mean survival times (RMST), and Accelerated failure time (AFT) models. Results: Among 2490 patients, 2197 were HBV negative, 218 had non-active HBV, and 75 had chronic HBV. Over a mean follow-up of 8.1 years, mortality and graft failure rates were highest in chronic HBV patients (49% and 37%), followed by non-active HBV (39% and 29%) and HBV-negative patients (30% and 20%). KM analysis revealed significantly lower overall survival rates for chronic HBV and non-active HBV groups compared to HBV-negative patients (p = 0.006). RMST confirmed significant reductions in survival for the non-active group (12.57 vs. 14.17 years, p = 0.007). Cox regression and AFT models identified older recipient/donor age, Hepatitis-C-virus coinfection, and broad antigen mismatches as negative predictors, while living donors improved outcomes. Conclusions: While unadjusted Kaplan–Meier curves and RMST analysis suggested differences in patient and graft survival, further thorough multivariable AFT analysis did not show a significant association between non-active or chronic HBV infection and patient or graft survival after kidney transplantation. Full article

Chronic Hepatitis B Virus (HBV) infection remains a significant public health concern, particularly in Africa, where the burden is substantial. HBV is an enveloped virus, classified into ten phylogenetically distinct genotypes (A–J). Tests to determine HBV genotypes are based on full-genome sequencing or reverse hybridization. In practice, both approaches have limitations. Whereas diagnostic sequencing, generally using the Sanger approach, tends to focus only on the S-gene and yields little or no information on intra-patient HBV genetic diversity, reverse hybridization detects only known genotype-specific mutations. To resolve these limitations, we developed an Oxford Nanopore Technology (ONT)-based HBV diagnostic sequencing protocol suitable for clinical virology that yields both complete genome sequences and extensive intra-patient HBV diversity data. Specifically, the protocol involves tiling-based PCR amplification of HBV sequences, library preparation using the ONT Rapid Barcoding Kit (Oxford nanopore Technologies, Oxford, OX4 4DQ, UK), ONT GridION sequencing, genotyping using genome detective software v1.132/1.133, a recombination analysis using jpHMM (26 October 2011 version) and RDP5.61 software, and drug resistance profiling using Geno2pheno v2.0 software. We prove the utility of our protocol by efficiently generating and characterizing high-quality near full-length HBV genomes from 148 residual diagnostic samples from HBV-infected patients in the Western Cape province of South Africa, providing valuable insights into the genetic diversity and epidemiology of HBV in this region of the world. Full article

Ischemia/reperfusion (I/R) injury with severe cell death is a major complication involved in liver transplantation and resection. The identification of key regulators improving hepatocyte activity may provide potential strategies to clinically resolve I/R-induced injury. N⁶-methyladenosine (m⁶A) RNA modification is essential for tissue homeostasis and pathogenesis. However, the potential involvement of m⁶A in the regulation of hepatocyte activity and liver injury has not been fully explored. In the present study, we found that hepatocyte AlkB homolog H5 (ALKBH5) levels were decreased both in vivo and in vitro I/R models. Hepatocyte-specific ALKBH5 overexpression effectively attenuated I/R-induced liver necrosis and improved cell proliferation in mice. Mechanistically, ALKBH5-mediated m⁶A demethylation improved the mRNA stability of YTH N⁶-methyladenosine RNA-binding protein 1 (YTHDF1), thereby increasing its expression, which consequently promoted the translation of Yes-associated protein (YAP). In conclusion, ALKBH5 is a regulator of hepatic I/R injury that improves hepatocyte repair and proliferation by maintaining YTHDF1 stability and YAP content. The ALKBH5–m⁶A–YTHDF1–YAP axis represents promising therapeutic targets for hepatic I/R injury to improve the prognosis of liver surgery. Full article

Toceranib phosphate (toceranib) is approved for canine mast cell tumor treatment. However, no long-term response to toceranib in canine HSTCL has been reported. Here, we describe a case of a 10-year-old castrated mixed-breed dog that presented with a 3-month history of weight loss, polydipsia, and polyuria. The clinicopathological and imaging abnormalities included icterus, biliary obstruction, and splenomegaly with multiple diffuse splenic hypoechoic nodules. On day 21, a cholecystectomy was performed to remove the obstruction, followed by a liver biopsy and splenectomy. Cytology of the spleen and liver showed many small lymphocytes with intracytoplasmic granules (sGLs). Splenic and hepatic infiltration of neoplastic CD3/granzyme B-positive small cells and lymphocytic cholecystitis with granzyme B-negative small cells were noted. T-cell receptor gene clonal rearrangements were observed in the liver tissues. The dog was diagnosed with a hepatosplenic T-cell lymphoma (HSTCL) of sGLs concurrent with lymphocytic cholecystitis. The icterus resolved after surgery, but there was progressive elevation of liver enzyme levels. Toceranib was administered from day 39, resulting in decreased liver enzyme levels, and the dog remained in good condition. The dog stayed in remission after toceranib administration and survived for 460 days. Toceranib should be considered an effective treatment option for canine HSTCL. Full article

Solid organ transplant (SOT) recipients are at significant risk of hepatitis B (HB) virus (HBV) reactivation (HBVr). Despite the clinical significance of HBVr after solid organ transplantation, data on the risk factors for HBVr and vaccine effectiveness in SOT recipients with resolved HBV infection are limited. This study evaluated the risk factors for HBVr and the seroconversion rates after HBV vaccination in SOT recipients. Patients who had undergone solid organ transplantation and those with a resolved HBV infection were identified. We matched patients who experienced post-transplantation HBVr with those who did not. We also explored the characteristics and seroconversion rates of HBV-vaccinated patients following transplantation. In total, 1299 SOT recipients were identified as having a resolved HBV infection at the time of transplantation. Thirty-nine patients experienced HBVr. Pre-transplant HB surface antibodies (anti-HBs) positivity and allograft rejection within 3 months after transplantation were independently associated with HBVr. Among the 17 HBV-vaccinated patients, 14 (82.4%) received three or fewer vaccine doses, and 13 (76.5%) had seroconversion with positive anti-HBs results. Pre-transplant anti-HBs(−) status and allograft rejection were risk factors for HBVr in SOT recipients with a resolved HBV infection, and HBV vaccination after transplantation resulted in a high rate of anti-HBs seroconversion. HBV vaccination after transplantation should be considered to reduce the HBVr risk. Full article

Obesity is an unhealthy condition associated with various diseases characterized by excess fat accumulation. However, in China, the prevalence of obesity is 14.1%, and it remains challenging to achieve weight loss or resolve this issue through clinical interventions. Sanghuangpours vaninii (SPV) is a nutritional fungus with multiple pharmacological activities and serves as an ideal dietary intervention for combating obesity. In this study, a long-term high-fat diet (HFD) was administered to induce obesity in mice. Different doses of SPV and the positive drug simvastatin (SV) were administered to mice to explore their potential anti-obesity effects. SPV regulated weight, serum lipids, and adipocyte size while inhibiting inflammation and hepatic steatosis. Compared with the vehicle-treated HFD-fed mice, the lowest decreases in total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) were 9.72%, 9.29%, and 12.29%, respectively, and the lowest increase in high-density lipoprotein cholesterol (HDL-C) was 5.88% after treatment with different doses of SPV. With SPV treatment, the analysis of gut microbiota and serum lipids revealed a significant association between lipids and inflammation-related factors, specifically sphingomyelin. Moreover, Western blotting results showed that SPV regulated the toll-like receptor (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway in HFD-diet mice, which is related to inflammation and lipid metabolism. This research presents empirical proof of the impact of SPV therapy on obesity conditions. Full article