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Hearing loss is a frequently observed complication of type 2 diabetes (T2D). Emerging evidence has found that Chinese herbal medicine (CHM) can effectively treat chronic disease; nevertheless, it is unclear if adding CHM to the routine management of T2D would modify sequent risk of hearing loss. This cohort-based case-control study was conducted to address this issue. First, a total of 64,418 subjects aged 20-70 years, diagnosed with T2D between 2002 and 2011, were extracted from a nationwide health claims database. Among them, we identified 4516 cases of hearing loss after T2D by the end of 2013. They were then randomly matched to 9032 controls without hearing loss at a 1:2 ratio. Following conditional logistic regression, we found the addition of CHM to conventional care reduced the risk of developing hearing loss, with an adjusted odds ratio of 0.75 (95% confidence interval: 0.70-0.83). Specifically, taking CHM products for at least two years benefits T2D patients in lowering sequent risk of hearing loss. The findings herein implicated that integrating CHM into conventional care substantially correlated to lower risk of hearing loss for T2D patients, but further basic research is needed to secure the application of finished herbal products.

Refractoriness to antiseizure medications is still a major concern in the pharmacotherapy of epilepsy. For this reason, we decided to evaluate the combination of levetiracetam and cannabidiol, administered at a subthreshold dose, to limit the possible adverse effects of this phytocannabinoid. We administered levetiracetam (300 mg/kg/day, via osmotic minipumps), cannabidiol (120 mg/kg/day, injected once a day subcutaneously), or their combination for one week in epileptic rats. Saline-treated epileptic rats were the control group. Animals were monitored with video electroencephalography the week before and after the treatment. No changes were found in the controls. Levetiracetam did not significantly reduce the total seizure number or the overall seizure duration. Still, the overall number of seizures (p < 0.001, Duncan's new multiple range test) and their total duration (p < 0.01) increased in the week following treatment withdrawal. Cannabidiol did not change seizures when administered as a single drug. Instead, levetiracetam combined with cannabidiol resulted in a significant reduction in the overall number and duration of seizures (p < 0.05), when comparing values measured during treatment with both pre- and post-treatment values. These findings depended on changes in convulsive seizures, while non-convulsive seizures were stable. These results suggest that cannabidiol determined a remarkable potentiation of levetiracetam antiseizure effects at a subthreshold dose.

Glaucoma stands as a primary cause of irreversible blindness globally, characterized by the progressive dysfunction and loss of retinal ganglion cells (RGCs). While current treatments primarily focus on controlling intraocular pressure (IOP), many patients continue to experience vision loss. Therefore, the research focus has shifted to therapeutic targets aimed at preventing or delaying RGC death and optic nerve degeneration to slow or halt disease progression. Traditional ocular drug administration, such as eye drops or oral medications, face significant challenges due to the eye's unique structural and physiological barriers, which limit effective drug delivery. Invasive methods like intravitreal injections can cause side effects such as bleeding, inflammation, and infection, making non-invasive delivery methods with high bioavailability very desirable. Nanotechnology presents a promising approach to addressing these limitations in glaucoma treatment. This review summarizes current approaches involving neuroprotective drugs combined with nanocarriers, and their impact for future use.

Two copper(II) mixed ligand complexes with dicarboxylate bridges were prepared and studied, namely [Cu₂(μ-fu)(pmdien)₂(H₂O)₂](ClO₄)₂ (complex No. 5) and [Cu₂(μ-dtdp)(pmdien)₂(H₂O)₂](ClO₄)₂ (complex No. 6), where H₂fu = fumaric acid, pmdien = N,N,N',N″,N″ pentamethyldiethylenetriamine, and H₂dtdp = 3,3'-dithiodipropionic acid. The copper atoms are coordinated in the same mode by the tridentate pmdien ligand and oxygen of water molecules, and they only differ in the dicarboxylate bridge. This work is focused on the study of the inhibitory effect of these potential antimicrobial drugs on the activity of the most important human liver drug-metabolizing enzymes, cytochromes P450 (CYP), especially their forms CYP2C8, CYP2C19, and CYP3A4. The obtained results allow us to estimate the probability of potential drug interactions with simultaneously administrated drugs that are metabolized by these CYP enzymes. In conclusion, the presence of adverse effects due to drug-drug interactions with concomitantly used drugs cannot be excluded, and hence, topical application may be recommended as a relatively safe approach.

Human coronaviruses are a continuous threat to the human population and have limited antiviral treatments, and the recent COVID-19 pandemic sparked interest in finding new antiviral strategies, such as natural products, to combat emerging coronaviruses. Rapid efforts in the scientific community to identify effective antiviral agents for coronaviruses remain a focus to minimize mortalities and global setbacks. In this study, an essential oil derived from Myrtus communis L. (MEO) is effective against HCoV-229E and HCoV-OC43 virus infections in comparison to two FDA-approved drugs, Remdesivir and Nirmatrelvir. Gas-chromatography and mass spectrometry were used to identify the chemical composition of MEO. Slight antioxidant activity was observed in MEO, indicating a role in oxidative stress. A dose-response curve measuring the EC₅₀ indicates a high potency against HCoV-229E and HCoV-OC43 virus infections on Huh7.5 cells with low cytotoxicity using a PrestoBlue cell viability assay. Our findings demonstrate that MEO exhibits potent antiviral activity against HCoV-229E and HCoV-OC43 on Huh7.5 cells within a low-cytotoxicity range, but not on SARS-CoV-2. Artificial bacterial chromosome plasmids that expressed SARS-CoV-2 used for replicon-to determine viral replication and viral assembly/egress on HEK293T/17 cells-and virus-like particles on Huh7.5-AT cells-to determine viral entry and assembly/egress-showed no antiviral activity with MEO in comparison to Remdesivir. This study reveals the potential effectiveness of MEO as an alternative natural remedy to treat human coronaviruses and a potential antiviral agent for future coronavirus infections.

Background/objectives: Anemia is a global health issue affecting diverse populations, particularly older adults, and conventional treatments often show limited efficacy. This study aimed to evaluate the utilization and effectiveness of Sipjeondaebotang (SDT), a prescription drug used in traditional East Asian medicine, in treating various types of anemia.

Methods: A scoping review was conducted following Arksey and O'Malley's framework and PRISMA-ScR guidelines. Six electronic databases were searched for clinical studies on SDT, while focusing on human participants and excluding animal and cellular studies. Sixteen studies, including nine randomized controlled trials, two controlled clinical trials, two case series, and three case reports, involving 863 participants, were analyzed. These studies were primarily conducted in China, Korea, and Japan.

Results: According to the analysis, SDT improved hemoglobin levels across all types of anemia studied, with all controlled studies showing significant improvements compared with the control groups. Additionally, SDT reduced blood loss, improved recovery times, and decreased transfusion requirements in patients with post-operative anemia, with lower adverse event rates than those in the control groups. These findings suggest that SDT may enhance hematological parameters and improve overall patient outcomes.

Conclusions: In conclusion, SDT may be an effective treatment for anemia that improves hemoglobin levels and patient outcomes. However, further high-quality, large-scale studies are necessary to standardize SDT prescriptions, confirm the optimal treatment duration, and validate its efficacy and safety across different anemia types.

Background: Oenothera rosea L'Her Ex. Aiton, presenting antioxidant and anti-inflammatory activities, is traditionally used to treat bruises and headaches and as a healing agent. This study aimed to investigate whether its organic fraction (EAOr) has neuroprotective properties against neuroinflammation in the context of ischemia/reperfusion.

Methods: The chemical composition of EAOr was determined using HPLC techniques, and its neuroprotective activities were evaluated in a common carotid-artery ligation model for the induction of ischemia/reperfusion (I/R). The animals were supplemented with EAOR for 15 days. On the last day, the animals were rested for one hour, following which the common carotid-artery ligation procedure was performed to induce I/R. The neurological deficit was evaluated at 24 h after I/R using Bederson's scale, and the relative expression of inflammatory genes and structure of hippocampal neurons were analyzed at 48 h.

Results: The chemical analysis revealed five major compounds in EAOr: gallic acid, rutin, ellagic acid, and glucoside and rhamnoside quercetin. EAOr prevented neurological deficit 24 h after I/R; led to the early activation of the AIF and GFAP genes; reduced Nfkb1, IL-1beta, Il-6 and Casp3 gene expression; and protected hippocampal neurons.

Conclusions: Our findings demonstrate that EAOr contains polyphenol-type compounds, which could exert a therapeutic effect through the inhibition of neuroinflammation and neuronal death genes, thus maintaining hippocampal neurons.

Cystic fibrosis (CF) is the most common fatal genetic disease among Caucasian people, with over 2000 mutations in the CFTR gene. Although highly effective modulators have been developed to rescue the mutant CFTR protein, unresolved inflammation and persistent infections still threaten the lives of patients. While the central role of arachidonic acid (AA) and its metabolites in the inflammatory response is widely recognized, less is known about their impact on immunomodulation and metabolic implications in CF. To this end, here we provided a comprehensive analysis of the AA metabolism in CF. In this context, CFTR dysfunction appeared to complexly disrupt normal lipid processing, worsening the chronic airway inflammation, and compromising the immune responses to bacterial infections. As such, potential strategies targeting AA and its inflammatory mediators are being investigated as a promising approach to balance the inflammatory response while mitigating disease progression. Thus, a deeper understanding of the AA pathway dysfunction in CF may open innovative avenues for designing more effective therapeutic interventions.

In the ongoing battle against antibiotic-resistant bacteria, New Delhi metallo-β-lactamase-1 (NDM-1) has emerged as a significant therapeutic challenge due to its ability to confer resistance to a broad range of β-lactam antibiotics. This study presents a pharmacophore-based virtual screening, docking, and molecular dynamics simulation approach for the identification of potential inhibitors targeting NDM-1, a critical enzyme associated with antibiotic resistance. Through the generation of a pharmacophore model and subsequent virtual screening of compound libraries, candidate molecules (ZINC29142850 (Z1), ZINC78607001 (Z2), and ZINC94303138 (Z3)) were prioritized based on their similarity to known NDM-1 binder (hydrolyzed oxacillin (0WO)). Molecular docking studies further elucidated the binding modes and affinities of the selected compounds towards the active site of NDM-1. These compounds demonstrated superior binding affinities to the enzyme compared to a control compound (-7.30 kcal/mol), with binding scores of -7.13, -7.92, and -8.10 kcal/mol, respectively. Binding interactions within NDM-1's active site showed significant interactions with critical residues such as His250, Asn220, and Trp93 for these compounds. Subsequent molecular dynamics simulations were conducted to assess the stability of the ligand-enzyme complexes, showing low root mean square deviation (RMSD) values between 0.5 and 0.7 nm for Z1, Z2, which indicate high stability. Z2's compactness in principal component analysis (PCA) suggests that it can stabilize particular protein conformations more efficiently. Z2 displays a very cohesive landscape with a notable deep basin, suggesting a very persistent conformational state induced by the ligand, indicating robust binding and perhaps efficient inhibition. Z2 demonstrates the highest binding affinity among the examined compounds with a binding free energy of -25.68 kcal/mol, suggesting that it could offer effective inhibition of NDM-1. This study highlights the efficacy of computational tools in identifying novel antimicrobial agents against resistant bacteria, accelerating drug discovery processes.

Dehydroepiandrosterone and its sulfate are the most abundant steroids in humans. The metabolism of dehydroepiandrosterone can differ significantly depending on the organ or tissue and the subtype of steroid receptors expressed in it. For dehydroepiandrosterone, as a precursor of all steroid hormones, intracrine hormonal activity is inherent. This unique feature could be beneficial for the medicinal application, especially for the local treatment of various pathologies. At present, the clinical use of dehydroepiandrosterone is limited by its Intrarosa^® (Quebec city, QC, Canada) prasterone) 6.5 mg vaginal suppositories for the treatment of vaginal atrophy and dyspareunia, while the dehydroepiandrosterone synthetic derivatives Triplex, BNN 27, and Fluasterone have the investigational status for the treatment of various diseases. Here, we discuss the molecular targets of dehydroepiandrosterone, which open future prospects to expand its indications for use. Dehydroepiandrosterone, as an oral drug, is surmised to have promise in the treatment of osteoporosis, cachexia, and sarcopenia, as does 10% unguent for skin and muscle regeneration. Also, 5-androstenediol, a metabolite of dehydroepiandrosterone, is a promising candidate for the treatment of acute radiation syndrome and as an immunostimulating agent during radiopharmaceutical therapy. The design and synthesis of new 5-androstenediol derivatives with increased bioavailability may lead to the appearance of highly effective cytoprotectors on the pharmaceutical market. The argumentations for new clinical applications of these steroids and novel insights into their mechanisms of action are discussed.