In drug development and clinical application, drug-drug interaction (DDI) prediction is crucial for patient safety and therapeutic efficacy. However, traditional methods for DDI prediction often overlook the structural features of drugs and the complex interrelationships between them, which affect the accuracy and interpretability of the model. In this paper, a novel dual-view DDI prediction framework, DAS-DDI is proposed. Firstly, a drug association network is constructed based on similarity information among drugs, which could provide rich context information for DDI prediction. Subsequently, a novel drug substructure extraction method is proposed, which could update the features of nodes and chemical bonds simultaneously, improving the comprehensiveness of the feature. Furthermore, an attention mechanism is employed to fuse multiple drug embeddings from different views dynamically, enhancing the discriminative ability of the model in handling multi-view data. Comparative experiments on three public datasets demonstrate the superiority of DAS-DDI compared with other state-of-the-art models under two scenarios.

UNASSIGNED: Urinary tract infections (UTIs) are a prevalent health challenge characterized by the invasion and multiplication of microorganisms in the urinary system. The continuous exploration of novel therapeutic interventions is imperative. Advances in research offer hope for revolutionizing the management of UTIs and improving the overall health outcomes for individuals affected by these infections.
UNASSIGNED: This review aimed to provide an overview of existing treatments for UTIs, highlighting their strengths and limitations. Moreover, we explored and analyzed the latest therapeutic modalities under clinical development. Finally, the review offered a picture into the potential implications of these therapies on the future landscape of UTIs treatment, discussing possible advancements and challenges for further research.
UNASSIGNED: Comprehensions into the pathogenesis of UTIs have been gleaned from foundational basic science studies, laying the groundwork for the exploration of novel therapeutic interventions. The primary source of evidence originates predominantly from animal studies conducted on murine models. Nevertheless, the lack of clinical trials interferes the acquisition of robust evidence in humans. The challenges presented by the heterogeneity and virulence of uropathogens add an additional layer of complexity, posing an obstacle that scientists and clinicians are actively grappling with in their pursuit of effective solutions.

Oral lichenoid lesions or reactions (OLLs/OLRs), which are clinical and histological contemporaries of the traditional oral lichen planus (OLP), had already garnered a great deal of attention in the literature. In contrast to idiopathic OLP, OLLs frequently have a definite, recognizable initiating component. Although a cursory clinical and histological evaluation of lesions frequently demonstrates numerous similarities with OLP, relatively new data has demonstrated that distinct features exist and serve as the foundation for the majority of categories. Although many systemic pharmaceuticals can lead to end oral lichenoid reactions, medications for diabetes, hypertension, nonsteroidal anti-inflammatory, antimalarial, and antifungal treatments are frequently blamed. Oral drugs, metallic dental restorations, acrylates, composite resins, glass ionomer cement, cinnamates, flavorings, and other chemical substances have all been associated when in direct contact. The objective of the case report is to elaborate the correlation between the oral lichenoid reaction and the use of hair dye. The incident under consideration is significant because the majority of past reports of allergic reactions to hair dye involved the face and scalp rather than the oral cavity. This report recommends that oral physicians inquire about the patient\'s use of cosmetics during history-taking whenever dealing with abrupt inflammatory responses in the orofacial area in order to diagnose and treat lesions more efficiently.

Schistosomiasis is a tropical parasitic disease, in which the major clinical manifestation includes hepatosplenomegaly, portal hypertension, and organs fibrosis. Clinically, treatment of schistosomiasis involves the use of praziquantel (PZQ) and supportive care, which does not improve the patient\'s outcome as liver injuries persist. Here, we report for the first time the effect of N-acetyl-L-cysteine (NAC) and/or praziquantel (PQZ) on S. mansoni, hepatic granuloma, serum markers for liver function and oxidative damage in acute schistosomiasis. Infected mice were divided into control, NAC, PZQ and NAC+PZQ groups and uninfected into control and NAC groups. After infection, NAC (200 mg/kg/day) was administrated until the 60th day and PZQ (100 mg/kg/day) from the 45th to the 49th day, both orally. On day 61, the mice were euthanized for serum markers for liver function. Worms were recovered, fragments of intestine employed to ascertain the oviposition pattern, and the liver was used for histopathological analysis, histomorphometry, egg and granuloma counting and oxidative stress marker assays. NAC reduced the burden of worms and eggs and increased the dead eggs in intestinal tissue. NAC+PZQ brought about reduction in granulomatous infiltration and NAC and/or PZQ reduced levels of ALT, AST, and alkaline phosphatase and increased albumin. NAC, PZQ or NAC+PZQ reduced levels of the superoxide anion, lipid peroxidation and protein carbonyl and increased sulfhydryl groups. The reduction in parasitological parameters, granulomatous inflammation and oxy-redox imbalance suggests NAC acts as a adjuvant in treatment of acute experimental schistosomiasis.

From a systematic review framework, we assessed the preclinical evidence on the effectiveness of drug combinations for visceral leishmaniasis (VL) treatment. Research protocol was based on the PRISMA guideline. Research records were identified from Medline, Scopus and Web of Science. Animal models, infection and treatment protocols, parasitological and immunological outcomes were analysed. The SYRCLE\'s (SYstematic Review Center for Laboratory Animal Experimentation) toll was used to evaluate the risk of bias in all studies reviewed. Fourteen papers using mice, hamster and dogs were identified. Leishmania donovani was frequently used to induce VL, which was treated with 23 drugs in 40 different combinations. Most combinations allowed to reduce the effective dose, cost and time of treatment, in addition to improving the parasitological control of Leishmania spp. The benefits achieved from drug combinations were associated with an increased drug\'s half-life, direct parasitic toxicity and improved immune defences in infected hosts. Selection, performance and detection bias were the main limitations identified. Current evidence indicates that combination chemotherapy, especially those based on classical drugs (miltefosine, amphotericin B antimony-based compounds) and new drugs (CAL-101, PAM3Cys, tufisin and DB766), develops additive or synergistic interactions, which trigger trypanocidal and immunomodulatory effects associated with reduced parasite load, organ damage and better cure rates in VL.

Chagas disease (CD) is endemic in Latin America. Drugs available for its treatment are benznidazole (BZ)/nifurtimox (NF), both with low efficacy in the late infection and responsible for several side effects. Studies of new drugs for CD among natural products, and using drug combinations with BZ/NF are recommended. Silibinin (SLB) is a natural compound that inhibits the efflux pump (Pgp) of drugs in host cell membranes, causes death of trypanosomatids, has anti-inflammatory activity, and was never assayed against T. cruzi. Here, in vitro and in vivo activities of SLB, SLB+BZ, and BZ against T. cruzi Y strain were evaluated. Cytotoxicity of SLB in VERO cells by the MTT method revealed IC50 of 250.22 μM. The trypanocidal activity evaluated by resazurin method in epimastigotes showed that SLB 25 μM inhibited parasite growth. SLB IC50 and selectivity index (SI) for amastigote were 79.81 μM and 3.13, respectively. SLB100+BZ10 showed higher parasite inhibition (91.44%) than SLB or BZ. Swiss mice infected with Y strain were treated with SLB, SLB+BZ, and BZ. Parasitemia was evaluated daily and 90, 180, and 240 days after treatment in surviving animals by hemoculture, blood qPCR, and after euthanasia, by qPCR in heart tissue. SLB monotherapy was not able to control the parasitemia/mortality of the animals. Parasitological negativation of 85.7-100% was observed in the experimental groups treated with SLB+BZ. Although SLB had shown activity against T. cruzi in vitro, it was not active in mice. Thus, the results of the therapeutic effect observed with SLB+BZ may be interpreted as a result from BZ action.

In this study, we demonstrated the potential associative effect of combining conventional amphotericin B (Amph B) with gallic acid (GA) and with ellagic acid (EA) in topical formulations for the treatment of cutaneous leishmaniasis in BALB/c mice. Preliminary stability tests of the formulations and in vitro drug release studies with Amph B, GA, Amph B plus GA, EA, and Amph B plus EA were carried out, as well as assessment of the in vivo treatment of BALB/c mice infected with Leishmania major After 40 days of infection, the animals were divided into 6 groups and treated twice a day for 21 days with a gel containing Amph B, GA, Amph B plus GA, EA, or Amph B plus EA, and the negative-control group was treated with the vehicle. In the animals that received treatment, there was reduction of the lesion size and reduction of the parasitic load. Histopathological analysis of the treatments with GA, EA, and combinations with Amph B showed circumscribed lesions with the presence of fibroblasts, granulation tissue, and collagen deposition, as well as the presence of activated macrophages. The formulations containing GA and EA activated macrophages in all evaluated parameters, resulting in the activation of cells of the innate immune response, which can generate healing and protection. GA and EA produced an associative effect with Amph B, which makes them promising for use with conventional Amph B in the treatment of cutaneous leishmaniasis.

Antihistamines and glucocorticoids (GCs) are often used together in the clinic, in several inflammatory-related situations. Even though there is no clear rationale for this drug association, the clinical practice is based on the assumption that due to their concomitant antiinflammatory effects, there should be an intrinsic benefit in their coadministration. Our group has studied the molecular interaction between the histamine H1 receptor and the glucocorticoid receptor (GR) signaling pathways, showing an enhancing effect on GC-induced GR transcriptional activity induced by antihistamines. We hypothesize that the existence of this synergistic effect could contribute in reducing the GCs clinical doses, ineffective by itself but effective in combination with an antihistamine. This could result in a therapeutic advantage as the GC-desired effects may be reinforced by the addition of an antihistamine and, as a consequence of the dose reduction, GC-related adverse effects could be reduced or at least mitigated. Here we discuss the potential therapeutic applications of this cotreatment seeking to evaluate its usefulness, especially in inflammatory-related conditions.

BACKGROUND: Oral lichenoid lesions or reactions (OLLs/OLRs) are clinical and histological contemporaries of the classical oral lichen planus (OLP) that have generated a lot of debate in literature. In contrast to the idiopathic nature of OLP, OLLs are often associated with a known identifiable inciting factor. A superficial examination of these lesions clinically and histologically often reveals many similarities with OLP, but recent data indicate that distinguishable features do exist and form the basis of most classifications.
OBJECTIVE: This paper attempts to collate available data in English literature on OLLs, highlight distinguishing features clinically and histologically and reflect on the malignant transformation potential and treatment modalities of the condition.
METHODS: A comprehensive search of medical and dental databases including PubMed, Ovid, Cochrane, Pubget, Researchgate, and non-medical search engines were utilized for the review. The search words included \"oral lichen planus\", \"oral lichenoid lesions\", \"oral drug reactions\", \"lichenoid dysplasia\", and \"adverse effects of dental materials\".
RESULTS: OLLs seem to grossly underrated and most cases were clubbed as OLP. Definite clinical and histological features were uncovered to establish the identity of this lesion. Associations with dental restorative materials, drugs, and medications have been conclusively proven in the etiology of this condition. Specific markers are being utilized to diagnose the condition and monitor its progress.
CONCLUSIONS: Substantial differentiating features were uncovered to delineate OLLs as a separate entity with definite etiology, pathogenesis, and a high malignant transformation rate compared with OLP.