β-Cyclodextrin-functionalized Zr-sulfonamide MOF novel pH-responsive nano platform for breast and lung cancer.

Advances on botanicals targeting programmed cell death in acetaminophen-induced liver injury.

Adverse events related to buspirone: a real-world pharmacovigilance study using the FAERS database.

Therapeutic potential of quercetin in hepatocellular carcinoma: Mechanisms, challenges, and clinical insights

Central to the schema therapy model is the development of early maladaptive schemas due to unmet emotional needs in childhood. Recently, focus has shifted towards positive constructs in schema therapy, including early adaptive schemas or positive schemas and positive schema modes, such as the "healthy adult" and "happy child." This scoping review explores theoretical perspectives, assessment, and therapeutic use of these positive constructs in schema therapy. The PRISMA-ScR methodology was followed, using predefined search terms and databases (OVID, EBSCO, Mednar). After identifying 345 studies, 144 remained post-deduplication. Articles were screened by two reviewers, and disagreements were settled by consensus among the research team. A total of 47 records were included. A growing interest in positive constructs within schema therapy was found since 2011. The healthy adult and the happy/contented child were the most frequently discussed constructs, followed by early adaptive schemas and positive coping. Key findings include a strong relationship between the healthy adult mode and psychological well-being, while negative correlations exist with psychopathology. Assessment focuses on questionnaires like the Schema Mode Inventory and Young Positive Schema Questionnaire, however empirical evidence for positive schema therapy interventions is lacking. Limitations include diverse publication types and preliminary findings. Recommendations for further research include clarifying the healthy adult mode construct, exploring positive coping, and integrating positive constructs into schema therapy for improved therapeutic outcomes.

Topical application of Clostridium butyricum by an anaerobic hydrogel for accelerated diabetic wound healing through selective bacteria inhibition and ROS scavenging.

Bridged PROTAC, DNA-based PROTAC and hydrophobic tag technologies for targeted protein degradation.

Peloids are natural materials widely used in balneotherapy and dermatological treatments because of their physicochemical and mineralogical properties. Despite Serbia’s long tradition of spa-based pelotherapy, comprehensive data on the chemical and radiological characteristics of local peloids remain limited. In this study, peloid samples from 13 spa locations across four regions of Serbia were systematically investigated. The aim was to determine their physicochemical properties, elemental composition, and natural radioactivity, to assess their suitability and safety for therapeutic use. The analyzed samples exhibited pronounced variability in pH (6.59–9.52), electrical conductivity (77.5–6610 μS/cm), salinity (below detection limit to 4%), and total dissolved solids, reflecting diverse geological and hydrochemical properties. Inductively coupled plasma optical emission spectrometry revealed site-specific variations in macro- and microelements, influenced primarily by local lithology and sedimentary environments, with limited indications of anthropogenic inputs. Gamma spectrometric analysis showed that the activity concentrations of naturally occurring radionuclides (226Ra, 232Th, 40K, 238U, 235U, 210Pb) were within ranges commonly reported for therapeutic muds worldwide, while anthropogenic 137Cs was generally low. Radiological hazard indices were below internationally recommended safety limits. A preliminary screening of dermal exposure to potentially toxic elements indicated no significant noncarcinogenic risk (HI < 1) and acceptable carcinogenic risk (TCR) levels. Overall, this study provides a comprehensive chemical and radiological baseline for Serbian peloids, supporting their safe use in controlled therapeutic and wellness applications and highlighting the importance of site-specific characterization for quality assessment.

Nitric oxide (NO) treated radioresistant tumors by relieving hypoxia and blocking DNA repair, but its nonselective toxicity has precluded therapeutic use. Here, we introduce a radioresistant tumor-selective NO nanogenerator that releases NO exclusively within the irradiated field. We identified BNN6 as a uniquely radiosensitive NO donor and loaded it into Glucose-Regulated Protein 78 (GRP78)-targeted nanocarrier to obtain PBTN, exploiting the overexpression of GRP78 in radioresistant cancers for selective accumulation. Upon irradiation, BNN6 undergoes one-electron reduction to release NO exclusively within the irradiated volume. NO combines radiation-induced reactive oxygen species to form peroxynitrite, provoking tumor DNA breaks while simultaneously suppressing DNA repair. In CT26 tumor-bearing mice, the combination of radiotherapy with PBTN and anti-PDL1 antibody achieved a tumor growth suppression of 96.5% and 80% survival at 40 days post-treatment. This tumor-targeted, irradiation-triggered NO nanogenerator thus offers a safe, precise, and translatable strategy to overcome radioresistance.

ABSTRACT The relationship between gut microbiota and human health has become one of the focal point in medical research. Probiotics, which modulate the gut microbiome, hold considerable promise for both prophylaxis and therapeutic intervention. This requires deeper insights into the kinetic changes and molecular mechanisms upon probiotic entry into the body. In this study, we utilized advanced molecular imaging to delineate the in vivo kinetic dynamics of two Lacticaseibacillus paracasei Zhang ( L. paracasei Zhang, LPZ) formulations: a liquid culture and a lyophilized powder. Our results provide new insights into the gastrointestinal transit and growth kinetics of the different probiotics formulations. Strikingly, the liquid LPZ achieved its peak growth phase within a relatively short period of 6 to 8 h post-ingestion, culminating in a 270- to 680-fold increase in residues at the 24th hour post-ingestion when compared to the lyophilized powder LPZ. Furthermore, during peak in vivo replication, LPZ enhanced gut microbial diversity and enriched beneficial commensal communities. Functionally, LPZ ingestion attenuated virulence factors while upregulating carbohydrate-active enzymes. Notably, LPZ significantly reduced xanthine levels, a metabolite associated with hyperuricemia, thereby providing a mechanistic basis for the observed relief from gout symptoms. This supports the mechanism of prior clinical findings and paves the way for future clinical trials and therapeutic use of LPZ and related probiotics. IMPORTANCE The innovation of this study lies in visualizing the kinetic changes of two Lacticaseibacillus paracasei Zhang ( L. paracasei Zhang, LPZ) formulations (a liquid culture and lyophilized powder) within the gastrointestinal tract. It was found that liquid LPZ proliferates in vivo with a higher retention rate. Furthermore, we also found that when liquid LPZ reaches its peak proliferation phase in vivo , it not only effectively promotes the proliferation of other beneficial bacteria and the production of their metabolites but also generates more carbohydrate-active enzymes while reducing virulence factors, thereby amplifying the functions of LPZ. Meanwhile, we observed that liquid LPZ significantly reduces the production of xanthine in vivo , indicating its potential to lower uric acid . In light of the aforementioned findings, we herein propose the concept of “probiotikinetics.” These results provide new insights into the intake of LPZ, along with important evidence for its application in healthy populations.

Tripterygium wilfordii is a traditional Chinese medicinal herb with a long history of therapeutic use but remains controversial in modern medicine because of its potent toxicity. Among its diverse chemical constituents, the diterpenoid triptolide and the triterpenoid celastrol have emerged as prominent compounds due to their remarkable pharmacological activities, including antitumor, immunosuppressive, anti-obesity, and neuroprotective effects. However, their clinical translation is limited by toxicity concerns and restricted natural availability. This review systematically summarizes the medicinal history and chemical constituents of T. wilfordii, with particular emphasis on the pharmacological mechanisms, structural modification strategies, and recent advances in the biosynthesis of triptolide and celastrol. In addition, we discuss perspectives on toxicity mitigation and lead compound development, aiming to provide theoretical guidance and valuable references for modern drug development and the green manufacturing of T. wilfordii -derived resources.

Effective management of perioperative pain remains one of the major clinical priority in surgical care due to its impact on the patient recovery, quality of life, as well as healthcare outcomes.The variability of the drug plasma concentration, increased systemic adverse effects as well as poor adherence of patients are the results of traditional modes of delivery of analgesics, such as the oral and parenteral route of delivery. TS has intruded through the transdermal drug delivery systems that imply a method of applying a treatment regimen that enables drug releases across the skin surface to the circulatory system over time. These possess a longer analgesic efficacy, a greater pharmacokinetic steadiness, and a reduced requirement of a repeated dose. The fentanyl patches, buprenorphine patches and the lidocaine patches have become some of the most researched transdermal analgesics. Orally ingesting the lidocaine patches would merely provide the local analgesia of the opioid solely with a low systemic exposure and then the patches that would produce the best analgesia in the long-term are the Fentanyl and buprenorphine patches. The clinical and pharmacological descriptions have shown that the patches are involved in multimodal analgesic systems in perioperative units because they maintain constant plasma drug levels and reduce the procedure of systemic opioid administration. Transdermal fentanyl patches have been labelled as effective in the multimodal analgesic regimen in the treatment of post operational pain in several surgery procedures. The use of buprenorphine patches provides a prolonged analgesic effect with desirable safety characteristics, including a reduced neurotoxicity level and low dose level when patients experience renal impairment. This has been done in despite of the encouraging outcomes of the lidocaine patches despite their frequent use in alleviating the severity of the neuropathic aches in the selected surgical procedures. The advantages of transdermal delivery include that first-pass metabolism does not occur, it does not require invasiveness, the therapeutic drug dose is retained and elevates adherence. Despite these benefits, there is never any other aspect of clinical tools such as delayed onset of action, source of patients, and probable effects of opioid use in clinical use, which is not an insignificant part of therapy decision making. The paper is a review of pharmacological and clinical properties of fentanyl, buprenorphine and lidocaine transdermal patches on the analgesia, in the perioperative period, and their therapeutic use in the existing multimodal analgesia programs.

As a result of industrial development, an increase in the number of vehicles, as well as human economic activity, a threat has emerged of large amounts of xenobiotics entering the environment and living organisms. With the deterioration of the environmental situation, including in Russia, the probability of human diseases caused by exposure to environmental factors has increased. This study demonstrates the possibility of using dried vegetables (carrots, beets, pumpkin) for the development of products intended for therapeutic and preventive use. The complex-forming ability of dried vegetables with respect to heavy metals was determined using model solutions. The best results in reducing the concentration of lead and cadmium ions were shown by dried carrots: 80.98% (p ≤ 0.001) and 65.18% (p ≤ 0.001), respectively. Formulations of flour confectionery products were developed with partial replacement of flour by dried carrot and pumpkin at concentrations of 5% and 10%. Sensory analysis showed that samples with the addition of 5% carrot and pumpkin demonstrated the best results. The physicochemical quality indicators of fortified pancakes were determined: samples with the addition of dried carrot exhibited a slight increase in titratable acidity compared to the control sample, which may be due to the presence of organic acids in the additives. Slight changes in moisture content were also identified in the model samples, especially when dried carrot was introduced into the formulation, which is explained by its high water-binding capacity. By calculation, it was established that the introduction of dried vegetable powders into the formulations of flour confectionery products reduced the energy value of the finished products by 22-133.8 kcal.

Dexamphetamine, a central nervous system stimulant, is increasingly prescribed to women of childbearing age, yet data on its safety in pregnancy, particularly for narcolepsy, remains limited. This case series examined pregnancy outcomes in 10 women with narcolepsy or idiopathic hypersomnolence at the Royal Brisbane and Women's Hospital who were prescribed dexamphetamine during pregnancy. Six women continued therapy throughout pregnancy. Apart from one case complicated by congenital CMV infection, all pregnancies progressed to the late third trimester with favourable neonatal outcomes. No cases of pre-eclampsia were observed; one woman developed gestational hypertension. All neonates had normal Apgar scores, with the exception of two where the Apgars were not recorded. However, no neonates required additional ventilatory support. Our findings suggest that therapeutic dexamphetamine use for narcolepsy may not be associated with adverse obstetric or neonatal outcomes. Individualised counselling is essential to balance maternal functional needs against potential pregnancy risks.

Inclusion bodies (IBs) in Escherichia coli were once regarded as undesirable aggregates of misfolded proteins, but are now increasingly recognised as functional biomaterials. Here, we show that the N-terminal p40 domain of a lytic polysaccharide monooxygenase from Caldibacillus cellulovorans acts as a scaffold for producing functional inclusion bodies. This property was demonstrated across diverse proteins, including the fluorescent protein mCherry, three industrially relevant enzymes, and the antimicrobial peptide ZXR-2. The p40 domain consistently promoted IB formation under a wide range of induction conditions, and the resulting protein nanoparticles retained enzymatic activity, could be reused over multiple reaction cycles, and, when fused to ZXR-2, exhibited both antimicrobial and cytotoxic activities. Biophysical analyses revealed that IB size and morphology were influenced by cultivation parameters, highlighting the tunability of p40-mediated assemblies. Comparative analyses underscored the structural robustness of p40-driven IBs and their ability to support diverse protein contexts. While not intended for direct therapeutic use, these results emphasise the potential of p40 IBs as a platform technology for in vitro studies, biocatalysis, and other biotechnological applications. These findings establish the p40 fusion domain as a reliable scaffold for functional inclusion body production in E. coli, providing a foundation for future applications of IBs as versatile biotechnological tools. KEY POINTS: • p40 serves as a versatile scaffold for active protein aggregates in E. coli. • Cultivation parameters modulate aggregates accumulation and physical properties. • p40 fusions form recyclable nanobiocatalysts and stabilise antimicrobial peptides.

The immunomodulatory effect of chicoric acid on cyclophosphamide-mediated gonadal dysfunction in male rats: Cross-talk between sirtuin-1, HMGB1/RAGE/TLR4 axis, and PI3K/Akt/mTOR signaling.

Nanobodies are emerging as attractive biopharmaceuticals due to their small size, stability and target specificity. However, their therapeutic use has largely been restricted to extracellular targets because of a lack of efficient delivery methods. This limitation is particularly relevant for diseases caused by dysfunctional intracellular proteins, such as cystic fibrosis. Here we show that cell-permeable nanobodies can modulate an intracellular disease-relevant target: the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel carrying the common F508del mutation. By combining a CFTR-binding nanobody with cell-penetrating peptides, we achieved intracellular delivery in cystic fibrosis bronchial epithelial cells. The delivered nanobody stabilizes misfolded F508del-CFTR, promotes its maturation and trafficking to the apical membrane and restores chloride channel activity. Moreover, the cell-permeable nanobody enhances the efficacy of approved CFTR modulator drug combination in primary airway epithelial cultures from patients with cystic fibrosis. These findings establish cell-permeable nanobodies as promising biopharmaceuticals for intracellular protein targeting and therapeutic modulation.

Advanced extraction to targeted delivery: A holistic review of technological innovations and therapeutic mechanisms of Ginkgo biloba extract.

Natural compounds represent approximately 35% of the pharmaceutical market, gaining prominence in the treatment of various diseases. Among them is chrysin, a flavonoid with notable antimicrobial and immunomodulatory activities. However, its low aqueous solubility and chemical instability limit its therapeutic use, highlighting the need for more soluble pharmaceutical carriers or derivatives, as well as patent analysis to map technologies and therapeutic development opportunities. Therefore, this study aimed to identify and explore trends in therapeutic strategies related to the action of chrysin and its derivatives in different pathologies, as well as their potential to increase clinical efficacy through pharmaceutical technologies. A technological survey was conducted on 36 patents registered between 1999 and 2025 in different databases. The analysis revealed peaks in patent applications in 2019 and 2024, with China as the main country and universities as the primary type of applicant. The patents demonstrated that chrysin and its derivatives exhibit complex immunological and pharmacological activities, acting on multiple cellular targets and signaling pathways. These include the inhibition of enzymes and proteins, modulation of inflammatory pathways, gene regulation, and other mechanisms. This pharmacological diversity of chrysin reinforces its relevance in patent applications, proving its efficacy and enabling new applications or therapeutic combinations.

In 2018, malaria remained a leading cause of morbidity and mortality in the Democratic Republic of the Congo, accounting for 44% of all outpatient visits and 22% of deaths. This led to the development of the strategic plan for 2020-2023. To meet the objectives of this renewed plan, a monitoring and evaluation program focusing on performance indicators was established. This study aimed to assess the malaria control performance indicators in Kinshasa. A descriptive cross-sectional study used the National Malaria Control Program dataset of the period 2020-2023 to analyze malaria data from 23 HZ (Health Zone) in Kinshasa. Diagnostic, therapeutic, and preventive use of LLINs (long-lasting insecticidal nets) and sulfadoxine-pyrimethamin-based IPT (intermittent preventive treatment among pregnant women) indicators were evaluated following the targeted thresholds established in the strategic plan for 2020-2023. Malaria was present in all studied HZ from 2020 to 2023, with a heterogeneous distribution. The malaria incidence during the study period was 30%, with an upward trend in both suspected and confirmed cases, peaking in 2022 and showing no further fluctuations thereafter. The proportion of LLINs distributed to pregnant women during antenatal care visits was 62%, 61%, 45%, and 88% in 2020, 2021, 2022, and 2023, respectively. A total of 83.1% of suspected malaria cases were diagnosed using RDT (Rapid Diagnosis Test), and confirmed malaria cases received antimalarial treatment. The objectives of the 2020-2023 strategic plan were only partially achieved, and no HZ reached 100% diagnosis by RDT, with only four HZs reaching at least 95% of the target. Thirty-four HZs were able to benefit from 95% treatment with antimalarial drugs.