Chronic hepatitis B virus (HBV)-infected patients may exhibit liver fibrosis and other pathological changes despite normal alanine aminotransferase (ALT). This study aimed to assess the efficacy and safety of tenofovir amibufenamide (TMF) in chronic HBV-infected patients with normal ALT levels.

The ongoing PROMOTE study (NCT05797714) is the first prospective, multicenter, randomized, open-label, blank-controlled clinical trial involving chronic HBV-infected patients with normal ALT levels. Participants were randomized in a 1:1 ratio to receive either TMF (TMF group) or no treatment (blank control group). The primary efficacy endpoint was the proportion of participants achieving HBV DNA levels <20 IU/mL at 48 weeks.

A total of 197 participants were enrolled, with 95 in the TMF group and 102 in the blank control group. At 48 weeks, a significantly greater proportion of participants in the TMF group achieved HBV DNA levels <20 IU/mL compared with the control group (74.2% vs. 9.0%, P < 0.001). The TMF group demonstrated more pronounced reductions in HBV DNA (−2.63 vs. −0.22 log10 IU/mL, P < 0.001), HBsAg (−0.07 vs. −0.04 log10 IU/mL, P = 0.02), and ALT levels (−14.09% vs. 0%, P = 0.003) compared with the blank control. In the TMF group, the proportion of participants with high-normal ALT levels (20–40 IU/L) was reduced. No significant differences were observed between the groups in creatinine, glomerular filtration rate, bone turnover biomarkers, lipid profiles, or phosphorus levels.

TMF treatment demonstrates significant efficacy in chronic HBV-infected patients with normal ALT levels and shows a favorable safety profile regarding bone, renal, and lipid parameters. The PROMOTE study is ongoing, and further results at 96 and 144 weeks are expected to provide additional insights.

Leishmaniasis is a dangerous yet neglected tropical disease affecting a vast population of the world. Several medicinal plants and their constituents (natural products/phytochemicals) have been considered of prime importance for the management of leishmaniasis over the years. The present review sheds light on the molecular mechanisms of the constituents obtained from medicinal plants that are pre-clinically effective against leishmaniasis. Various mechanisms by which medicinal plant-derived natural products elicit their action against leishmaniasis are illustrated in the literature. The mechanisms identified include: disruption of cytoplasmic and mitochondrial membranes, induction of apoptosis and autophagy, modulation of gene expression and immunological pathways, pro-oxidant effects (disrupting redox balance) with mitochondrial dysfunction, cell cycle arrest, impaired cellular bioenergetics, i.e., adenosine triphosphate production and coagulation of cellular contents within Leishmania parasites. Future phytochemical and pharmacological (especially clinical) studies are necessary to further understand the mechanistic details of medicinal plant-derived natural compounds and to develop new phytotherapeutic entities from nature against leishmaniasis.

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare and highly aggressive embryonal tumor that predominantly affects infants and young children. This malignancy arises from primitive neuroectodermal cells and exhibits heterogeneous differentiation into various embryonic tissues. Due to its rarity and complexity, diagnosing and managing AT/RT present significant challenges. Recent studies have summarized the key features of cerebellar and supratentorial AT/RT cases; however, critical gaps remain in understanding their diffuse leptomeningeal variants and long-term functional outcomes. Here, we report a case of a two-year-old child diagnosed with cerebellar AT/RT, who presented with vomiting and gait instability. The patient underwent a gross total resection followed by adjuvant radiotherapy and chemotherapy. Despite achieving radiological remission, the patient survived for only eight months and experienced severe neurological deficits, including persistent ataxia and recurrent infections. This case highlights the disconnect between surgical success and long-term quality of life. It underscores the importance of integrating molecular diagnostics and palliative care to address the multifaceted burden of AT/RT.

Metabolic syndrome (MetS) is associated with a plethora of different comorbidities. Exploring its key molecular mechanisms, such as advanced glycation end product and its receptor (AGE/RAGE) pathway, holds great potential. Numerous sources agree that targeting the AGE/RAGE pathway is a potential therapeutic strategy for MetS. However, the regulation of AGE/RAGE by microRNAs (miRNAs) in the context of MetS is still poorly understood. This review aimed to provide a systematic picture of the influence of miRNAs on AGE/RAGE in the context of MetS, with a particular focus on its ligands and receptors. This review achieves this in two ways: through an inductive “bottom-up” approach realized by a classical descriptive literature search, and through a deductive/synthetic “top-down” approach based on carefully selected miRNA profiling studies in MetS and its comorbidities. Although the initial inductive approach allowed the identification of some miRNAs of interest, almost all articles on this topic focus on the regulation of processes exclusively involved in atherogenesis. The new deductive approach has broadened the research horizon: It has enabled the discovery of new promising miRNAs and allowed for ranking different comorbid pathologies in MetS according to the degree of miRNA dysregulation of AGE/RAGE. Thus, in addition to atherosclerosis, significant miRNA dysregulation of AGE/RAGE was also described in MetS, particularly in immune cells, as well as in subcutaneous adipose tissue in obesity. This review, along with the novel approaches to systematizing the data contained therein may contribute to the understanding of MetS pathogenesis and the search for targets for the treatment of MetS.

This review presents the latest evidence on the link between genetic single nucleotide polymorphisms and dental caries, highlighting key genes and pathways involved, introducing foundational concepts, and discussing essential methodological considerations for future research. Several genes have been identified as significantly associated with caries experience, including those related to tooth mineral tissues, taste perception, salivary composition and flow, and immune response. Epistatic interactions appear to be crucial in explaining genetic influence. Inconsistencies in the literature are attributed to variations in caries classification, age groups, ethnic backgrounds, limited statistical power, and linkage disequilibrium. Population stratification often confounds results, and few studies adequately control for genetic ancestry. Ensuring Hardy-Weinberg equilibrium and accounting for linkage disequilibrium are essential to avoid bias. Bonferroni corrections for multiple comparisons are fundamental but rarely applied, contributing to inconsistent findings. In conclusion, genetic epidemiology studies suggest that dental caries has a genetic component, accounting for significant individual differences in disease risk.

The importance of putative folate-biopterin metabolic interactions lies in the role they may play in the expression of several clinically relevant phenotypes. However, to date, clinical studies on folate-biopterin interactions have been limited. The purpose of this article was to highlight the close relationship between these two cofactors, which share structural similarities and exhibit overlapping metabolic pathways. This folate-biopterin crosstalk has generated several ideas and hypotheses that are critical to advancing the biochemical understanding of several important and seemingly disparate clinical and/or biologically important phenotypes. These phenotypes include melanization/pigmentation, phenylketonuria, autism, neural tube defects, affective disorders, and vascular disease. This review provides a timely, integrated overview of this important area of biochemistry, which is under-represented in the literature and would benefit from further scientific and clinical investigation using improved metabolite-specific analytical methodologies applied to clinically relevant questions.

Patients with chronic hepatitis B virus (HBV) infection in the immune-tolerant phase may still experience hepatic inflammation and disease progression, and could benefit from early antiviral treatment. This study aimed to investigate changes in the cumulative hepatitis B surface antigen (HBsAg)/HBV DNA ratio in immune-tolerant patients during the transition to the immune-active phase, and to evaluate its potential in predicting the risk of disease progression.

This longitudinal study included 127 untreated immune-tolerant patients, who were followed for up to 10 years. An independent cohort of 109 subjects was retrospectively enrolled for external validation. The relationship between the cumulative HBsAg/HBV DNA ratio and the duration of immune tolerance or transition to the immune-active phase was examined. The predictive value of the ratio was assessed and validated.

The relationship between the cumulative HBsAg/HBV DNA ratio and disease progression risk showed a non-linear pattern: below a ratio of 1.791, the risk of disease progression decreased rapidly as the ratio increased; above 1.791, the risk plateaued. The area under the curve for predicting disease progression was 0.67, 0.64, and 0.85 for cumulative HBsAg, HBV DNA, and the HBsAg/HBV DNA ratio, respectively. Multivariable Cox regression analysis revealed the cumulative HBsAg/HBV DNA ratio as an independent predictor of disease progression, with higher ratios associated with a lower risk. Prediction models incorporating this ratio were developed and externally validated, demonstrating strong performance and clinical utility.

The cumulative HBsAg/HBV DNA ratio is an independent factor influencing the duration of immune tolerance and shows superior predictive performance. It may serve as a valuable marker for assessing the risk of disease progression in patients with chronic HBV infection.

Various devices are used to study the unique electrical properties of acupuncture points (APs), with Voll’s electropuncture diagnostics (EAV) occupying a prominent role. The technical design of EAV allows for the testing of drugs to determine their individual selection and dosages. However, the physiological basis of this phenomenon remains unclear. This study investigated the feasibility of evaluating the electrodermal activity of APs to determine the daily dose of ribavirin using electroacupuncture according to the Voll diagnostic system in patients with long COVID.

This blind, randomized, placebo-controlled trial included 101 patients (aged 16 to 50) who met the definition of long COVID and were examined using an EAV testing system that measures the electrodermal activity of APs. Ribavirin was tested at the APs with established decreased electrical impedance readings to determine the daily doses. Fifty-two participants were randomized to the experimental group, and forty-nine to the placebo group. These patients were considered for data analysis.

The results of this study demonstrated the feasibility of using EAV to identify APs with decreased levels of electrodermal activity, followed by medicament testing (MT) of different ribavirin doses to restore the electrodermal activity at these points.

The results indicated that the tested doses of ribavirin in patients with long COVID correlate with electrodermal activity at certain APs along specific meridians. Higher doses of the drug were associated with lower electrodermal activity readings during MT using the EAV diagnostic system. However, further clinical and instrumental studies are needed to evaluate the clinical application of MT in the assessment of long COVID.