Deciphering the complexity of the chemicals in food packaging materials using molecular networks.

Chemicals from packaging materials might be transferred into food resulting in consumer exposure. Identifying these migrated chemicals is highly challenging and crucial to perform their safety assessment, usually starting by the understanding of the chemical composition of the packaging material itself. This study explores the use of the Molecular Networking (MN) approach to support identification of the extracted chemicals. Two formulations of bioplastics were analyzed using Liquid Chromatography hyphenated to High-Resolution Mass Spectrometry. Data processing and interpretation using a conventional manual method was performed as a point of comparison to understand the power of MN. Interestingly, only the MN approach facilitated the identification of unknown chemicals belonging to a novel oligomer series containing the azelaic acid monomer. The MN approach provided a faster visualization of chemical families in addition to the highlight of unrelated chemicals enabling to prioritize chemicals for further investigation improving the safety assessment of packaging materials.

Uncovering the mechanisms of Zhubi decoction against rheumatoid arthritis through an integrated study of network pharmacology, metabolomics, and intestinal flora.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhubi Decoction (ZBD) is a modified formulation derived from the classic traditional Chinese medicine prescription "Er-Xian Decoction" documented in the esteemed "Clinical Manual of Chinese Medical Prescription". While the utilization of ZBD has exhibited promising clinical outcomes in treating rheumatoid arthritis (RA), the precise bioactive chemical constituents and the underlying mechanisms involved in its therapeutic efficacy remain to be comprehensively determined. AIM OF THE STUDY: This study aims to systematically examine ZBD's pharmacological effects and molecular mechanisms for RA alleviation. MATERIALS AND METHODS: Utilizing the collagen-induced arthritis (CIA) rat model, we comprehensively evaluated the anti-rheumatoid arthritis effects of ZBD in vivo through various indices, such as paw edema, arthritis index, ankle diameter, inflammatory cytokine levels, pathological conditions, and micro-CT analysis. The UPLC-MS/MS technique was utilized to analyze the compounds of ZBD. The potential therapeutic targets and signaling pathways of ZBD in the management of RA were predicted using network pharmacology. To analyze comprehensive metabolic profiles and identify underlying metabolic pathways, we conducted a serum-based widely targeted metabolomics analysis utilizing LC-MS technology. Key targets and predicted pathways were further validated using immunofluorescent staining, which integrated findings from serum metabolomics and network pharmacology analysis. Additionally, we analyzed the gut microbiota composition in rats employing 16 S rDNA sequencing and investigated the effects of ZBD on the microbiota of CIA rats through bioinformatics and statistical methods. RESULTS: ZBD exhibited remarkable efficacy in alleviating RA symptoms in CIA rats without notable side effects. This included reduced paw redness and swelling, minimized joint damage, improved the histopathology of cartilage and synovium, mitigated the inflammatory state, and lowered serum concentrations of cytokines TNF-α, IL-1ß and IL-6. Notably, the effectiveness of ZBD was comparable to MTX. Network pharmacology analysis revealed inflammation and immunity-related signaling pathways, such as PI3K/AKT, MAPK, IL-17, and TNF signaling pathways, as vital mediators in the effectual mechanisms of ZBD. Immunofluorescence analysis validated ZBD's ability to inhibit PI3K/AKT pathway proteins. Serum metabolomics studies revealed that ZBD modulates 170 differential metabolites, partially restored disrupted metabolic profiles in CIA rats. With a notable impact on amino acids and their metabolites, and lipids and lipid-like molecules. Integrated analysis of metabolomics and network pharmacology identified 6 pivotal metabolite pathways and 3 crucial targets: PTGS2, GSTP1, and ALDH2. Additionally, 16 S rDNA sequencing illuminated that ZBD mitigated gut microbiota dysbiosis in the CIA group, highlighting key genera such as Ligilactobacillus, Prevotella_9, unclassified_Bacilli, and unclassified_rumen_bacterium_JW32. Correlation analysis disclosed a significant link between 47 distinct metabolites and specific bacterial species. CONCLUSION: ZBD is a safe and efficacious TCM formulation, demonstrates efficacy in treating RA through its multi-component, multi-target, and multi-pathway mechanisms. The regulation of inflammation and immunity-related signaling pathways constitutes a crucial mechanism of ZBD's efficacy. Furthermore, ZBD modulates host metabolism and intestinal flora. The integrated analysis presents experimental evidence of ZBD for the management of RA.

Profiles, exposure assessment and expanded screening of PAHs and their derivatives in one petroleum refinery facility of China.

This study investigated environmental distribution and human exposure of polycyclic aromatic hydrocarbons (PAHs) and their derivatives in one Chinese petroleum refinery facility. It was found that, following with high concentrations of 16 EPA PAHs (∑Parent-PAHs) in smelting subarea of studied petroleum refinery facility, total derivatives of PAHs [named as XPAHs, including nitro PAHs (NPAHs), chlorinated PAHs (Cl-PAHs), and brominated PAHs (Br-PAHs)] in gas (mean= 1.57 × 104 ng/m3), total suspended particulate (TSP) (mean= 4.33 × 103 ng/m3) and soil (mean= 4.37 × 103 ng/g) in this subarea had 1.76-6.19 times higher levels than those from other subareas of this facility, surrounding residential areas and reference areas, indicating that petroleum refining processes would lead apparent derivation of PAHs. Especially, compared with those in residential and reference areas, gas samples in the petrochemical areas had higher ∑NPAH/∑PAHs (mean=2.18), but lower ∑Cl-PAH/∑PAHs (mean=1.43 × 10-1) and ∑Br-PAH/∑PAHs ratios (mean=7.49 × 10-2), indicating the richer nitrification of PAHs than chlorination during petrochemical process. The occupational exposure to PAHs and XPAHs in this petroleum refinery facility were 24-343 times higher than non-occupational exposure, and the ILCR (1.04 × 10-4) for petrochemical workers was considered to be potential high risk. Furthermore, one expanded high-resolution screening through GC Orbitrap/MS was performed for soils from petrochemical area, and another 35 PAHs were found, including alkyl-PAHs, phenyl-PAHs and other species, indicating that profiles and risks of PAHs analogs in petrochemical areas deserve further expanded investigation.

High-Throughput RPLC-MS/MS Quantification of Short- and Medium-Chain Fatty Acids.

Short- and medium-chain fatty acids (SMCFA) are monocarboxylic acids with a carbon chain length of 1-12 carbon atoms. They are mainly produced in humans by the gut microbiota, play crucial metabolic roles, are vital for intestinal health, and have multifaceted impact on immune and neurological functions. Accurate detection and quantification of SMCFA in different human biofluids is achieved using 3-nitro phenylhydrazine (3-NPH) derivatization of the free fatty acids followed by reverse phase liquid chromatography (RPLC) separation and detection by tandem mass spectrometry (MS/MS). Here, we describe the simultaneous measurement of 14 SMCFA and lactate in detail. All 3-NPH-SMCFA-hydrazones are separated in less than 5 min with an 8-min total run time (injection-to-injection). Linear dynamic range over 0.1-500 µM is achieved for most SCFAs, while it is 0.05-100 µM for MCFAs. Validation of the procedure depicts good linearity (R2 > 0.98) and repeatability (CV ≤ 20%). The lower limit of detection (LLOD) is 10-30 nM. The lower limit of quantification (LLOQ) is 50-100 nM for most analytes, while it is 0.5 µM for acetate. In conclusion, the method offers several benefits compared to alternative methods regarding throughput, selectivity, sensitivity, and robustness.

Rapid Analysis of Sterols in Blood-Derived Samples.

Dysregulations of cholesterol biosynthesis are known to be associated with several pathologies. Due to the rapid growth of clinical investigations in this research area, a specific, fast, and valid method for analyzing cholesterol, its precursors, and metabolites is required. Here, we describe a rapid method for sample preparation, separation, and quantification of sterols in blood-derived samples using polymeric solid phase extraction followed by gas chromatography-mass spectrometry. The validated method demonstrates a reliable quantification of cholesterol, its precursors, and metabolites.

Detection and Characterization of Clonal Hematopoiesis.

Clonal hematopoiesis (CH) is the age-related expansion of hematopoietic stem cell clones resulting from the acquisition of somatic point mutations or mosaic chromosomal alterations (mCAs). It is linked to adverse systemic effects, including hematologic malignancies, cardiovascular diseases, metabolic disorders, as well as liver and kidney ailments, ultimately contributing to elevated overall mortality.Given its diverse biological and clinical implications, the identification of clonal hematopoiesis holds significance in various contexts. While traditionally centered on mutations associated with myeloid malignancies, stem/progenitor cell involvement has been documented for various lymphoid malignancies, including T-cell lymphoma, chronic lymphocytic leukemia (CLL), and follicular lymphoma (FL). Lymphoid CH (L-CH) involves a broader spectrum of genes and occurs at a lower prevalence, resulting in reduced mutation prevalences per gene. This characteristic poses challenges for efficient CH detection.The major strategies to identify CH are whole exome sequencing (WES), whole genome sequencing (WGS), or targeted sequencing. Targeted sequencing allows for much higher sequencing depth compared to WES and WGS because of the focus on genes known to be associated with CH and therefore allows detecting potential variants at low frequencies with high precision. Here, we describe an error-corrected targeted sequencing approach for detection of CH in bone marrow (BM) or peripheral blood (PB) samples, which we have successfully established and used in various cohorts. This protocol includes the process of DNA isolation from PB and BM samples, library preparation with molecular tags including quality control steps and computational analysis including variant filtering.

Enzymatic interlocking aptamer-micelles for enhanced cellular internalization and nucleus-targeted cancer phototherapy.

Multifunctional micelles that permit both diagnosis and treatment present enormous advantage and potential for precision medicine. However, the inherent complexities and structural instability of these systems often cause unsatisfactory targeting and therapeutic performances. Herein, by ingenious design of a 2,5-bis(2-thienyl)pyrrole (SNS) modifier to covalently link with AS1411 aptamer and lipid segment, a simple strategy is proposed for one-step enzymatic preparation of interlocked aptamer-micelle (IApM) under bio-friendly conditions. The interlocked poly(SNS) skeleton in IApM can not only stabilize the micelle structure but also enhance near-infrared (NIR) absorption ability, thus further enhancing cellular internalization and photothermal therapy. In addition, the multivalent AS1411 aptamers tethered in the hydrophilic shell can simultaneously increase the specific binding affinity of DNA micelles and induce nucleus-targeted accumulation for DNA damage-triggered apoptosis. This DNA micelle achieves "best of both worlds" with enhanced biostability for cellular internalization and improved NIR photothermal conversion efficiency for nucleus-targeted therapy, which provides a promising formulation strategy for precision cancer treatment.

Identification of novel genetic variants associated with oral squamous cell carcinoma (OSCC) in South-West coast of India using targeted exome sequencing.

Oral squamous cell carcinoma (OSCC) is a subset of head and neck squamous cell carcinoma (HNSCC). This study explores the genetic landscape of oral squamous cell carcinoma (OSCC) in a cohort of 33 patients from Southern India using targeted exome sequencing. Our analysis revealed a diverse range of mutations across the cohort, with missense mutations being the most prevalent. Pathogenic mutations, as classified by ClinVar, exhibited significant individual variation, highlighting the heterogeneity of OSCC. Seventy-five genes were identified to harbor pathogenic or potentially pathogenic mutations, with notable recurrence in genes such as TP53, PDGFRA, and RAD50 among others. Comparison with high-frequency mutation genes in HNSCC from TCGA database revealed significant overlap, emphasizing the relevance of these mutations across different populations. Additionally, several novel mutations were identified, including those in CHD8, ITPKB, and HNF1A, shedding light on potential genetic risk factors specific to this population. Functional annotation and pathway analysis underscored the involvement of these mutated genes in various cancer-related pathways. Despite limitations such as sample size and the need for further validation, this study contributes to a deeper understanding of OSCC pathogenesis and highlights potential genetic markers for prognosis and targeted interventions, especially in the Indian context.

Bifunctional Nanocellulose@MOF composite aerogel for selective fluorescent detection and efficient removal of tetracycline.

The antibiotic tetracycline (TC) significantly pollutes water bodies, adversely impacting ecosystems and human health. In this work, a bifunctional platform for simultaneous detection and removal of TC was successfully constructed by in-situ growth of Zr-MOF in BC microspheres. The in-situ growth ensured the stability, while the design of the aerogel microspheres improved the processability, convenience, and recyclability. The macropores and mesopores in the aerogel microspheres significantly improved the molecular mass transfer efficiency, and the sensitivity and selectivity of TC detection and adsorption were improved due to the size-sieving effect of the abundant micropores of Zr-MOF and the supramolecular interaction of the ligand. Owing to the hierarchical pore structure, the adsorption capacity reaches as high as 317.6 mg/g. The enrichment during the adsorption process enhances the interaction between TC and Zr-MOF, thereby significantly improving the detection sensitivity of TC. As expected, BMAT3H5 has a LOD as low as 28 ± 0.012 nM and a KSV as high as 1.89 ± 0.001 × 106 M-1, providing excellent detection performance compared to other work in recent years. The good selectivity to TC was theoretically validated through simulations with Materials Studio software (MS). It provides a novel and practical bifunctional platform for efficient fluorescence detection and adsorption of TC, which has a broad application prospect in the fields of environmental monitoring, water treatment, and food safety testing.

An absolute quantification method for selected MFGM proteins in infant formula using targeted proteomics.

Milk fat globule membrane (MFGM) proteins are receiving increased attention due to their reported benefits for human health, particularly in infant populations. Challenges exist in MFGM protein quantification due to their low quantities, complex chemistry, interactions with other matrix components, and the high matrix complexity. In this study, a subset of four MFGM proteins were selected as relevant targets for identification and quantification in an infant formula (IF) matrix: butyrophilin, mucin 1, xanthine dehydrogenase/oxidase, and perilipin 2. An analytical protocol for absolute quantification of these four MFGM proteins in IF was successfully developed and validated. Additionally, the feasibility to apply the method in selected MFGM ingredients was also demonstrated. The method demonstrated good performance; high accuracy and robustness, low LOQ and uncertainty, while controlling the matrix effect. This study represents a report of an analytical method to quantify selected MFGM proteins in IF.

Study of phenanthrenes from their unique mass spectrometric behavior through quantum chemical calculations to liquid chromatographic quantitation.

Phenanthrenes and their derivatives have biological relevance owing to their antimicrobial, antioxidant, and cytotoxic effects on cancer cells. They can be efficiently analyzed through ultrahigh-performance liquid chromatography coupled to tandem high-resolution mass spectrometry (UHPLC-MS/HRMS). Herein, we first studied the unique fragmentation behavior of phenanthrenes based on direct infusion MS/HRMS analysis. As a newly described phenomenon, "organ pipe distribution", we found a structural connection linking their unique fragmentation pattern to serial H radical losses. The bonds responsible for this behavior were identified through quantum chemical calculations using a stepwise approach. Furthermore, the chromatographic aspect of this study was enhanced by developing, validating, and applying a new unscheduled targeted UHPLC-MS/HRMS method for quantifying phenanthrenes in Juncus compressus herb. Targeted compounds were efficiently separated within 4 min upon utilizing the Accucore C30 column, and the unscheduled targeted analytical approach afforded five new isomers. Compounds 1 (effususol), 3 (dehydroeffusol), and 6 (7-hydroxy-1-methyl-2-methoxy-5-vinyl-9,10-dihydrophenanthrene) had their linearity limits determined within 10-5000 nM, and Compounds 2 (effusol), 4 (juncusol), 5 (effususin A), and 7 (compressin A) within 25-5000 nM. The coefficients of variation for precision ranged from 1.4 % to 15.2 %. The obtained matrix effects and accuracy values were also within acceptable ranges. Compounds 2 (effusol) and 3 (dehydroeffusol) were present in both methanolic and dichloromethanolic extracts of Plants 1 and 3 at the highest concentrations. Furthermore, the relationship between phenanthrene fingerprints, obtained through ANOVA statistical analysis of quantitative data, and the geographical location of herbs was also established.

Advances in predicting breast cancer driver mutations: Tools for precision oncology (Review).

In the modern era of medicine, prognosis and treatment, options for a number of cancer types including breast cancer have been improved by the identification of cancer­specific biomarkers. The availability of high­throughput sequencing and analysis platforms, the growth of publicly available cancer databases and molecular and histological profiling facilitate the development of new drugs through a precision medicine approach. However, only a fraction of patients with breast cancer with few actionable mutations typically benefit from the precision medicine approach. In the present review, the current development in breast cancer driver gene identification, actionable breast cancer mutations, as well as the available therapeutic options, challenges and applications of breast precision oncology are systematically described. Breast cancer driver mutation­based precision oncology helps to screen key drivers involved in disease development and progression, drug sensitivity and the genes responsible for drug resistance. Advances in precision oncology will provide more targeted therapeutic options for patients with breast cancer, improving disease­free survival and potentially leading to significant successes in breast cancer treatment in the near future. Identification of driver mutations has allowed new targeted therapeutic approaches in combination with standard chemo­ and immunotherapies in breast cancer. Developing new driver mutation identification strategies will help to define new therapeutic targets and improve the overall and disease­free survival of patients with breast cancer through efficient medicine.

Targeting LINC00665/miR-199b-5p/SERPINE1 axis to inhibit trastuzumab resistance and tumorigenesis of gastric cancer via PI3K/AKt pathway.

Long noncoding RNAs (lncRNAs) serve as critical mediators of tumor progression and drug resistance in cancer. Herein, we identified a lncRNA, LINC00665, associated with trastuzumab resistance and development in gastric cancer (GC). LINC00665 was highly expressed in GC tissues and high expression of LINC00665 was correlated with poor prognosis. LINC00665 knockdown was verified to suppress migration, invasion, and resistance to trastuzumab in GC. Furthermore, we found that LINC00665 participates in the infiltration of naive B cells, mast cells, and T follicular helper (Tfh) cells. Mechanistically, LINC00665 was confirmed to regulate tumorigenesis and trastuzumab resistance by activating PI3K/AKt pathway. LINC00665 sponged miR-199b-5p to interact with SERPINE1 expression, resulting in the increase of phosphorylation of AKt, thus participating in the PI3K/AKt pathway. To summarize, LINC00665 facilitated the tumorigenesis and trastuzumab resistance of GC by sponging miR-199b-5p and promoting SERPINE1 expression, which further activated PI3K/AKt signaling; this finding reveals a new mechanism by which LINC00665 modulates tumor development and drug resistance in GC.

Differences in axillary response and treatment implications in HER2 positive node positive breast cancer during neoadjuvant HER2 targeted dual therapy.

Explore whether the axillary outcomes differ among HER2 positive subgroups receiving standard dual-targeted therapy, aiming to identify subgroups exhibiting enhanced sensitivity to NAT among HER2-positive/node-positive breast cancer patients. HER2 positive female patients with biopsy-proven node-positive disease from April 2020 to May 2023 were included. All patients underwent standard Neoadjuvant HER2-targeted dual therapy and axillary lymph node dissection (ALND) at Breast Surgery Center of Sichuan Cancer Hospital. Univariate and multivariate analyses were used to identify factors associate with axillary pathological complete response (ApCR). Statistical analysis and graphing were performed using SPSS 24.0 and GraphPad Prism 9.0 software. This study enrolled 215 HER2 positive patients with a total ApCR rate of 76.7%, which included 49 HER2 2+/FISH + and 166 HER2 3 + cases with approximate ApCR rates of 63.3% and 80.7% (P = 0.011). Univariate and multivariate analysis indicated that HER2 3 + disease (OR = 2.43, 95% CI 1.21-4.88, P = 0.012), Ki-67 ≥ 20% disease (OR = 3.00, 95% CI 1.26-7.13, P = 0.013) and NAC regimen of TCb (OR = 2.71, 95% CI 1.39-5.38, P = 0.004) were more likely to achieve ApCR. Further subgroup analysis revealed that HER2 3 + patients receiving TCb regimen showed the highest ApCR rate of 88% compared to other subgroups. HER2 3 + breast cancer had a higher ApCR rate than HER2 2+/FISH + breast cancer during Neoadjuvant HER2-targeted dual therapy. HER2 positive patients could benefit from NAC regimen of TCb in axillary response.

A Nanobody-based TRIM-away targets the intracellular protein degradation of African swine fever virus.

African swine fever virus (ASFV) is the causative agent of African swine fever (ASF), a hemorrhagic illness with high fatality rates in domestic pigs that has resulted in a substantial socio-economic loss and threatens the global pork industry. Very few safe and efficient vaccines or compounds against ASF are commercially available, thus developing new antiviral strategies is urgently required. Targeted protein degradation (TPD) has emerged as one of the most innovative strategies for drug discovery. In this study, we generate Nanobody-based TRIM-aways specifically binding with and targeting ASFV-encoded structural proteins p30, p54, and p72 for degradation. Furthermore, nanobody-based trim-aways exhibit robust viral structural protein degradation capabilities in ASFV-infected iPAM and MA104 cells through both proteasomal and lysosomal pathways, concurrently demonstrating potent anti-ASFV activity with less viral production. Our study highlights the Nanobody-based TRIM-away targeting viral protein degradation as a potential candidate for the development of a novel antiviral strategy against ASF.

111Ag phantom images with Cerenkov Luminescence Imaging and digital autoradiography within the ISOLPHARM project.

Targeted Radionuclide Therapy (TRT) is a medical technique exploiting radionuclides to combat cancer growth and spread. TRT requires a supply of radionuclides that are currently produced by either cyclotrons or nuclear research reactors. In this context, the ISOLPHARM project investigates the production of innovative radionuclides for medical applications. This production will be based on the forthcoming SPES facility at the Legnaro National Laboratories (LNL) of the National Institute for Nuclear Physics (INFN), an ISOL facility where high-purity radioactive beams will be used to produce carrier-free radiopharmaceuticals. Previous studies demonstrated that a significant amount of 111Ag, an innovative ß/γ emitter suitable for TRT with theranostic applications, can be obtained at the SPES facility. The present work describes the first imaging study on phantoms with 111Ag performed by the ISOLPHARM collaboration. This is a fundamental step to pave the way for the upcoming in vivo studies on the 111Ag-based radiopharmaceutical currently being developed. The imaging potential of this radionuclide was investigated by acquiring phantom images with Cerenkov Luminescence Imaging (CLI) and digital autoradiography (ARG).

Effect of rapamycin on hepatic metabolomics of non-alcoholic fatty liver rats based on non-targeted platform.

Rapamycin (Rapa) is an inhibitor of mTOR complex, and its therapeutic effect on liver function was examined in non-alcoholic fatty liver disease (NAFLD) rats here. And the possible mechanism of Rapa in NAFLD was preliminarily elucidated based on the non-targeted metabolomics analysis. Adult male SD rats were fed with a high-fat and high-cholesterol diet (HFD) to establish NAFLD model. For Rapa group, 0.8 mg/(kg.d) Rapa was given to the HFD rats. Ultra-performance liquid chromatography and Q-Tof-mass spectrometry (UPLC and Q-TOF/MS) analysis were applied for the identification of metabolites in the serum of rats, which were annotated using Kyoto Encyclopedia of Genes and Genomes (KEGG). NAFLD rats presented with disturbed liver function, lipid metabolism and oxidative stress, but Rapa exerted a mitigating influence on the disorders. The metabolite profile data identified 579 metabolites that varied remarkably between the Rapa and HFD groups, with the main classes of amino acids and peptides, benzene, lipids and fatty acids. The differential metabolites were mainly involved in biosynthesis of cofactors, bile secretion, and glycerophospholipid metabolism were mainly enriched. In conclusion, Rapa has a potential protective effect against HFD-induced NAFLD, its hepatoprotective effect may achieved through mediating bile secretion and glycerophospholipid metabolism.

Elucidation of endogenous and exogenous chemicals in maternal serum using high-resolution mass spectrometry.

The increasing exposure to environmental chemicals calls for comprehensive non-targeted analysis to detect unrecognized substances in human samples. We examined human serum samples to classify compounds as endogenous or exogenous using public databases and to explore the relationships between exposure markers and metabolic patterns. Serum samples from 84 pregnant women at 32 weeks gestation were analyzed using LC-QToFMS. Using the PubChemLite for Exposomics database, we annotated and classified 106 compounds (51 endogenous, 55 exogenous). The compound patterns were analyzed using three dimensional reduction methods: Principal Component Analysis (PCA), regularized Generalized Canonical Correlation Analysis (rGCCA), and Uniform Manifold Approximation and Projection (UMAP). OPTICS clustering applied to these methods revealed two distinct clusters, with 89 % of significant compounds overlapping between clusters. The detected exogenous compounds included dietary substances, phthalates, nitrogenous compounds, and parabens. Pathway enrichment analysis showed that chemical exposure was linked to changes in amino acid metabolism, protein and mineral transport, and energy metabolism. While we found associations between exposure and metabolite changes, we could not establish causality. Our approach of analyzing both exogenous and endogenous chemicals from the same dataset using PubChemLite database presents a new method for exposome research, despite limitations in sample size and peak annotation accuracy. These findings contribute to understanding multiple chemical exposures and their metabolic effects in human biomonitoring.

Targeted drug delivery via intrathecal pain pump for the treatment of malignant pain.

Cancer patients experience pain at significant rates but are often undertreated-it is estimated that less than 1% of eligible cancer pain patients receive appropriate targeted drug delivery to address their pain. Cancer pain is often managed with systemic opioid treatment; however, this approach is limited in treating pain adequately and carries significant side effect risk profiles. Successful treatment of pain is closely tied to better oncologic outcomes as well as better measures on assessments of quality of life for cancer patients. Placement of intrathecal pain pumps represent a safe and effective way to manage pain in cancer patients. We describe the process of placing intrathecal pain pumps in an interventional radiology suite. This method of pump placement represents a minimally invasive approach to long term and continuous pain relief. Intrathecal pain pumps help maximize pain control for patients experiencing refractory pain due to disease process or treatments associated with malignancy.

Biochanin-A co-crystal formulation improves bioavailability and ameliorates cerulein-induced pancreatitis by attenuating the inflammation.

Co-crystallization of a therapeutic ingredient with an appropriate co-former is a powerful technique to augment the physicochemical and pharmacokinetic properties and the effectiveness of Active Pharmaceutical Ingredients (APIs). Biochanin A (BCA), a flavonoid with medicinal potential, is limited by poor solubility and low oral bioavailability. This study aimed to design and develop a novel BCA-nicotinamide cocrystal as BCC to enhance BCA's oral bioavailability and explore its therapeutic potential for ameliorating cerulein-induced acute pancreatitis (CIAP) by elucidating the target identification utilizing tissue/serum metabolite profiles. The cocrystal was designed by the supramolecular synthon approach and characterized by single-crystal X-ray diffraction that confirms a robust three-dimensional hydrogen-bonded network of BCA and Nicotinamide (NCT) in the crystal. FT-IR and DSC were used to analyze the cocrystal's intermolecular interactions and thermal behavior. BCC exhibited enhanced solubility and drug release compared to BCA alone, resulting in enhanced oral bioavailability and pancreatic tissue concentration. Comparing BCC to BCA in the CIAP model, BCC therapy remarkably reduced cerulein-induced pancreatitis, evidenced by significant reductions in inflammation, acinar cell atrophy, and amylase levels in pancreatic tissues. Further, the cocrystal formulation also down-regulated the oxidative stress markers, inflammatory cytokines and macrophage-related proteins. The study has identified distinct metabolomic signatures linked with AP with the help of Orbitrap Exploris mass spectrometry, which could pave the way for creating focused diagnostic tools for a better prognosis. In conclusion, these results offer new insights into exploring mechanistic pathways associated with specific biomarkers and underscore BCC cocrystals as a promising approach to enhance BCA's therapeutic potential.