Rhupus syndrome, an overlap of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), is a rare condition characterized by heterogeneous clinical manifestations and difficult management. Conventional therapies, including glucocorticoids, disease-modifying anti-rheumatic drugs (DMARDs), immunosuppressants, and biologics, are often limited by drug intolerance and steroid-related complications. Molecular hydrogen (H2) has emerged as a potential adjuvant therapy due to its antioxidant and immunomodulatory properties. This report aimed to evaluate the clinical efficacy of H2 as an adjunct to rituximab in a patient with refractory Rhupus and multiple drug intolerances. We report a 47-year-old male with a 27-year history of rheumatoid arthritis, who subsequently developed systemic lupus erythematosus, fulfilling criteria for Rhupus syndrome. His disease course was complicated by multiple drug intolerances, including adverse reactions to methotrexate, sulfasalazine, hydroxychloroquine, azathioprine, leflunomide, and rituximab at standard dosing. Despite reduced-dose rituximab and mycophenolic acid, disease activity persisted and lupus nephritis was confirmed. In October 2023, oral molecular hydrogen capsule therapy was initiated as adjuvant treatment, resulting in significant clinical improvement, which was paralleled by characteristic changes in T- and B-cell subsets, normalization of anti-dsDNA antibody, erythrocyte sedimentation rate (ESR), and complement levels, and successful discontinuation of prednisone. Hydrogen therapy was well tolerated without major adverse effects. The patient developed avascular necrosis from prior corticosteroid use but recovered well after hip arthroplasty in January 2025. Disease control was sustained with mycophenolic acid and continued hydrogen therapy. This case suggests molecular hydrogen therapy as a potential adjuvant for refractory Rhupus with multiple drug intolerances, showing immune modulation, reduced inflammation, steroid withdrawal, and sustained control with low-dose rituximab. Further studies are needed to confirm its efficacy and standardize its use.

An intelligent molecularly imprinted sensing platform augmented by interval partial least squares for specific detection of mycophenolic acid in agricultural silage.

Integration of QuEChERS pretreatment and advanced liquid chromatography/mass spectrometry analysis for the broad-spectrum screening and simultaneous quantification of 15 mycotoxins in Citrus reticulata peel.

Solid-organ transplantation (for example, kidney or liver) and haematopoietic-stem-cell transplantation have revolutionized treatment of end-stage organ failure and haematological malignancies. However, long-term outcomes are often undermined by complications such as allograft rejection, graft-versus-host disease in haematopoietic-stem-cell recipients, opportunistic infections, adverse effects of drugs and decreased quality of life. Emerging evidence now highlights the gut microbiome and its metabolites (such as short-chain fatty acids) as a potentially modifiable factor influencing transplantation outcomes. Transplantation recipients frequently exhibit gut dysbiosis, which has been linked to graft function, risk of infection (for example, vulnerability to multidrug-resistant bacteria), immune-mediated complications and patient survival. Furthermore, pharmacomicrobiomics studies indicate that microorganisms can metabolize immunosuppressive drugs into less active forms (such as the conversion of the immunosuppressive drug tacrolimus into less active or toxic forms through keto-reduction, glucuronidation or deconjugation) or can activate prodrugs (such as the conversion of mycophenolate mofetil into mycophenolic acid), thereby modulating drug efficacy and safety. Here, we discuss how the intestinal ecosystem is altered and persistently shaped by transplantation-related factors and immunosuppression and how these changes correlate with clinical outcomes. We provide a perspective on leveraging microbiome insights, through biomarkers or microbiome-targeted interventions, to improve outcomes in solid-organ and stem-cell transplantation.

Non-targeted screening of emerging pollutants across wastewater and receiving waters: A case study in Eswatini.

CRISPR/Cas9-mediated development of Penicillium roqueforti strains deficient in roquefortine C and mycophenolic acid enables toxin-free blue cheese production.

Niosomes as a versatile nanocarrier for antiviral agents: Enabling delivery of both hydrophilic and hydrophobic drugs.

ObjectiveThe purpose of this study was to describe reports of congenital eye anomalies entered in the international pharmacovigilance database, with a particular focus on medications associated with this type of anomaly.Methods and analysisThis descriptive, retrospective study selected reports using the adverse reaction term ‘congenital eye disorders’ and included only those instances where at least one medication was documented as being administered via the transplacental route. Statistical analyses were performed using R software.ResultsWe extracted 2923 reports of eye anomalies in children exposed to medications in utero and ultimately selected 676 of these. Congenital anomalies of the eyelids (17.3%), lacrimal apparatus (9.4%) and orbit (1.1%) were the most common. The suspect medications highlighted in this study include teratogenic agents known to pose a risk of triggering eye anomalies such as valproic acid and mycophenolic acid. The list also includes medications with little or no reference in the literature to potential eye anomalies following in utero exposure, such as hydroxychloroquine and ondansetron.ConclusionThis study provides new data on in utero exposure to medications and congenital eye anomalies that can be severely debilitating. This is a descriptive study, with all the inherent limitations of the pharmacovigilance databases which are used for signal detection. This descriptive study does not allow us to conclude that there is a causal link between exposure to a given medication during pregnancy and congenital eye anomalies and is a basis for future studies using different data sources and/or other methods.

Background: Marine sponges and sponge-associated fungi are rich sources of bioactive compounds with pharmacological potential. However, the secondary metabolites of Vietnamese marine sponge-derived fungi have been poorly studied. Objective: The aim of this study was to investigate the low-molecular-weight compounds in the extract of Penicillium sp. 1901NT-2.53.1 fungus isolated from the Vietnamese marine sponge Cinachyrella sp., and the antiproliferative activity of the isolated compounds. Methods: The structures of isolated compounds were elucidated using spectroscopic methods. The cell viability effects of the compounds were evaluated using MTT assay. Molecular docking was performed using SwissDock. Results: UPLC-MS data suggested the presence of beauvericin, citreorosein, benzopyran and chlorotetracycline derivatives, 2-chloro-1,3,8-trihydroxy-6-(hydroxymethyl)anthracene-9,10- dione and ergosterol peroxide in the fungal extract. Chromatographic separation of the extract resulted in the isolation of three derivatives of mycophenolic acid (MPA), namely penicacids G and K and 4-hydroxy-MPA. Penicacid K was isolated from a natural source for the first time. Penicacid G inhibited the viability of human normal HaCaT keratinocytes with IC50 of 88.3 μM and 72.9 μM for 24 h and 48 h of treatment, respectively. Moreover, penicacid G arrested the proliferation of HaCaT keratinocytes. Both penicacids K and G can interact with the active site of IMPDH2, similar to other derivatives of MPA; however, the differences in their structures are important. Conclusion: Due to the selective action on cancer cells and good druggability, penicacid G may be interesting as an antiproliferative anticancer compound.

Mycophenolic acid (MPA) is a common immunosuppressant used in children post-orthotopic heart transplant (OHT). Multiple MPA dosing strategies exist, with limited reports of comparisons between dosing strategies and patient outcomes. We performed a retrospective review of heart transplant recipients ≤21 years from 2014 to 2022, comparing dose concordance and clinical outcomes of weight-based mycophenolate dosing (15mg/kg/dose every 12h) to body surface area (BSA)-based dosing (600mg/m2/dose every 12h). We analyzed 109 patients total (56% in the BSA-based cohort and 44% in the weight-based cohort). The BSA-based cohort received a higher total milligram dose (480 (IQR 200-563) vs. 636 (IQR 320-1000), p=0.005), mg/kg dose (14.5 (IQR 13.7-16.1) vs. 20.7 (IQR 16.4-25.8), p<0.001) and mg/m2 dose (382 (IQR 333-470) vs. 596 (IQR 572-612), p<0.001) compared to the weight-based cohort. The BSA-based cohort experienced a lower hazard of rejection (HR 0.2, 95% CI 0.1-0.4vs. weight-based) and a greater hazard for overall infection (HR 2.2, 95% CI 1.2-3.9). There was no significant difference in 1-year post-transplant mortality and incidence of post-transplant lymphoproliferative disorder (PTLD). This study demonstrates the discordance between two common mycophenolate dosing strategies (1200mg/m2/day vs. 30mg/kg/day) and its resultant impact on pediatric heart transplant-related outcomes. Further multicenter data would be useful to elucidate the impact on post-heart transplant morbidity and mortality.

Rationalized immunosuppressant dosing in kidney transplantation: Mycophenolate mofetil AUC monitoring and key updates on tacrolimus exposure.

In vitro recapitulation of drug metabolite partitioning into the bile and blood using the icHep system consisting of hepatocytes with an induced open-form bile canaliculus.

The consumption of nuts is widespread globally and constitutes a significant component of the human diet due to its nutritional value. However, the presence of mycotoxins in food products, including nuts, is a global public health concern. Mycotoxins are toxic metabolites produced by contaminating fungi such as Aspergillus spp. and Penicillium spp., which can contaminate crops during growth, harvesting, storage, or transport. The aim of this study was to conduct monitoring for the presence of mycotoxins in nuts already on the market. Specifically, secondary metabolites produced by Penicillium spp., including ochratoxin A, patulin, citrinin, cyclopiazonic acid, citreoviridin, griseofulvin, meleagrin, mycophenolic acid, penitrem A, roquefortine C, penicillins G and V, sulochrin, andrastin A, asterriquinone, chaetoglobosin A, cyclopenin, cyclopenol, and viridicatin, were investigated. Commercial products were purchased from various retail outlets in different formats, origins, and cultivation methods to assess potential influences of these factors on mycotoxin presence. Regarding Penicillium-toxins, 37% of the samples showed the presence of at least one of them, and 9% showed the simultaneous presence of two or more Penicillium-toxins. Peanuts had the highest incidence of Penicillium-toxin contamination, with at least one metabolite detected in 60% of the analyzed samples. The most common secondary metabolite among the samples was patulin (14%), while the secondary metabolite with the highest concentration was viridicatin in a walnut sample (151.40 ± 64.30 µg/kg). Besides Penicillium-toxins, aflatoxins were also analyzed with another validated LC-MS/MS method, but they were not detected in any sample. Although most Penicillium-toxins, and in particular patulin in nuts, are not currently regulated in the international legislation, they exert toxic effects on humans and animals, and their occurrence can represent a food safety risk.

BACKGROUNDKidney disease is a common complication in liver transplant (LT) recipients, contributing to substantial morbidity and mortality. Calcineurin inhibitors are associated with short- and long-term decline in kidney function.AIMTo assess how changes in immunosuppression over three decades have impacted the evolution of renal function in the first year post-LT.METHODSThis single-center, observational, retrospective study was conducted in a tertiary hospital in Madrid. Adult patients who received a first LT in our center from 1987 to 2019 were included. Patients with simultaneous or prior transplantation of another organ and patients who required re-transplantation, or were lost to follow-up or died during the first year after transplantation were excluded. The development of chronic kidney disease (CKD) pre-transplant or at the first year after LT was analyzed.RESULTSA total of 594 patients (median age: 52.9 years, 25th-75th percentiles = 45-59.08 years; 29.3% female) were included. At 1 year post-transplant, 290 (48.82%) patients had developed CKD. Older age [odds ratio (OR) = 1.03, 95%CI: 1.01-1.05], female sex (OR = 1.88, 95%CI: 1.23-2.89), pre-transplant renal dysfunction (RD) (OR = 2.69, 95%CI: 1.58-4.58), and treatment with cyclosporine A (CsA) (OR = 3.77, 95%CI: 2.45-5.78) were independent risk factors for CKD at 1 year after LT. In patients treated with tacrolimus (Tac) (n = 375), the combination of basiliximab and mycophenolic acid (MPA) resulted in decreased Tac blood levels (P < 0.001); additionally, MPA was associated with a lower incidence of RD in the first year (P = 0.016).CONCLUSIONAge, female sex, pre-transplant RD, and CsA are associated with increased risk of CKD within 1 year after LT. Addition of MPA to Tac is associated with lower RD incidence.

The Birch reduction, a classic method involving the partial reduction of aromatic rings using alkali metals in liquid ammonia, has played a pivotal role in the development of modern organic synthesis. This transformation enables the regioselective generation of substituted cyclohexa-1, 4- and 1, 3-dienes-particularly enol ethers-from benzene derivatives, offering unique access to synthetically valuable intermediates. Historically, it was the only viable route to such non-conjugated dienes, and its absence would have significantly delayed the synthesis of key bioactive molecules, including 19-norsteroids and early oral contraceptives. The reaction provides exceptional steric and electronic control, facilitating downstream transformations such as Diels-Alder cycloadditions, reductive alkylations, and stereoselective functionalizations. Furthermore, the integration of Birch-derived intermediates with organometallic chemistry-particularly Fe(CO)3 complexation-introduces facial differentiation, enabling enantioselective synthesis through "inorganic enzyme chemistry." This review highlights the mechanistic principles of the Birch reduction, its role in the synthesis of natural products such as mycophenolic acid, nootkatone, juvabione, gabaculine, and shikimic acid, and its evolving applications in stereocontrolled synthesis. The enduring utility of this method underscores its importance in both fundamental and applied organic chemistry.

ABSTRACT Cytarabine (ara-C) and fludarabine (F-ara-A) are key drugs in leukaemia treatment. SAMHD1 is known to confer resistance to ara-C and F-ara-A, and we previously identified ribonucleotide reductase inhibitors as indirect SAMHD1 inhibitors in a phenotypic screen. The inosine monophosphate dehydrogenase (IMPDH) inhibitor mycophenolic acid (MPA) was also a hit in this screen. IMPDH inhibitors (IMPDHi) have previously shown efficacy against KMT2A-rearranged (KMT2Ar) acute myeloid leukaemia (AML). We investigated whether IMPDH inhibition could enhance the effect of ara-C and F-ara-A in AML cell lines and primary AML samples, and whether this effect was linked to KMT2A status. We found that sensitivity to IMPDHi was independent of KMT2A status. IMPDHi synergized with ara-C and F-ara-A in a SAMHD1-dependent manner in a subset of AML cells, but not in acute lymphoblastic leukaemia cell lines. Mechanistically, IMPDHi depleted allosteric SAMHD1 activators GTP and dGTP, thereby increasing active triphosphate metabolites in SAMHD1-proficient, but not SAMHD1-deficient, cells. Our findings suggest that the addition of IMPDHi to ara-C and F-ara-A may have therapeutic benefits in some AML cases.

ABSTRACTOrgan transplant recipients are at high risk of developing chronic infection when exposed to hepatitis E virus (HEV), which can rapidly progress to liver fibrosis and cirrhosis. Macrophages play a key role in the response to the infection and disease progression. However, the interactions amongst immunosuppressants, macrophages, the course of HEV infection and activation of inflammatory response remain unclear. In this study, we generated M0, M1 and M2 macrophages from the human THP‐1 cell line. These macrophages were then infected with HEV and treated with different immunosuppressants. We visualised viral infection using laser confocal microscopy, and quantitatively analysed viral replication and inflammatory responses by bulk sequencing, RT‐qPCR, ELISA and Western blotting. We found that the M1 inflammatory macrophages exhibited the highest, while M2 macrophages had the lowest levels of viral RNA. Genome‐wide transcriptome analysis indicated that viral, inflammation and immunity‐related pathways were predominantly upregulated by HEV infection. Dexamethasone exerted potent inhibitory effects on inflammatory response in macrophages. Mycophenolic acid (MPA) demonstrated inhibitory effects on viral replication, IL‐1β and TNF‐α expression, whereas mTOR inhibitors had the opposite effects, and tacrolimus showed no clear effect. In conclusion, immunosuppressants can differentially affect HEV replication and the subsequent inflammatory responses in macrophages.

Human Metapneumovirus (HMPV) is a leading cause of respiratory tract infections worldwide, with no approved antiviral treatments or vaccines currently available. This study explores the potential of repurposing SARS-CoV-2 ligands as therapeutic agents against HMPV through a comprehensive computational approach. The present study investigates three ligands, Salvianolic Acid C, Mycophenolic Acid, and Aurintricarboxylic Acid for their binding affinity, stability, and interaction dynamics with the HMPV protein structure using molecular docking, molecular dynamics (MD) simulations, binding free energy calculations, and principal component analysis (PCA). The results revealed that Salvianolic Acid C formed the most stable complex with HMPV protein model, exhibiting consistent RMSD values (5–6 Å), low residual fluctuations, and a favorable binding free energy of -26.12 kcal/mol. Hydrogen bond analysis further supported its stability, with a 20.97% occupancy between GLU96 of HMPV protein model and Salvianolic Acid C. In contrast, Mycophenolic Acid and Aurintricarboxylic Acid demonstrated weaker binding and higher conformational heterogeneity. PCA and free energy landscape (FEL) analysis confirmed the stable binding mode of Salvianolic Acid C, with well-defined, deep energy basins, while the other ligands exhibited fragmented and less stable conformations. Furthermore, these findings highlight that Salvianolic Acid C as a promising candidate for anti-HMPV therapy, leveraging its stable binding and favorable thermodynamic properties. This study provides a foundation for the development of targeted antiviral treatments against HMPV protein model, addressing a critical unmet need in respiratory disease management for further experimental validation.

ABSTRACT Objectives Non-infectious uveitis (NIU) is an immune-mediated, vision-threatening disease often requiring immunomodulatory therapy. We systematically evaluate the efficacy and safety of immunomodulatory therapies for the management of NIU. Methods A systematic review and meta-analysis were conducted following PRISMA guidelines. PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched up to December 2024. Randomized, controlled trials (RCTs) assessing the efficacy and safety of immunomodulatory agents for uveitis were included. Bayesian network meta-analyses were conducted to compare treatments across trials, while frequentist meta-analyses were performed to estimate the absolute treatment failure rate at month 6 and the overall SAEs rate. Risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool. Results Sixteen randomized controlled trials, involving 11 immunomodulatory therapies, were included from 6097 records retrieved. Among them, adalimumab plus corticosteroids was associated with significant reduction in hazard of treatment failure over time (HR 0.51, 95% CrI: 0.24–0.95) compared with corticosteroids monotherapy. The estimated overall treatment failure rate at month 6 was 37.6%, and the number of SAE was around 10.1%. No significant differences were observed in treatment failure rates at month 6, changes in BCVA or number of SAEs across treatments. Conclusions Adalimumab plus corticosteroids significantly prolonged the relapse-free period compared with corticosteroids monotherapy. Mycophenolic acid showed favorable trend in both efficacy and safety. Despite immunomodulatory treatment, the risk of uveitis relapse still remains and warrants continued attention.

C3 glomerulopathy (C3G) is a rare kidney disease characterized by dysregulation of the alternative pathway of the complement system. Efficacy of the available treatment options is quite limited, and almost half of the patients progress to kidney failure within 10 years. Moreover, the disease is known to recur in 42-100% of patients after kidney transplantation. Conventional treatment approaches typically include a renin angiotensin system blocker and a combination of glucocorticoids and mycophenolic acid derivatives. Successful use of eculizumab has been reported in aggressive disease forms. Response to these strategies have been quite variable, and efficacy of eculizumab has not been shown in slowly progressive forms of C3G. New agents such as iptacopan and pegcetacoplan look very promising. Notably, use of both agents was recently approved by the United States Food and Drug Administration. Herein we review novel treatment strategies for patients suffering from C3G with a focus on agents targeting complement system.