Future Of Medicine Research Articles

Genetic medicine of familial and hereditary pancreatic cancer: Recent update in the era of precision cancer medicine

AbstractIn Japan, 5 years have passed since the initiation of precision cancer medicine, and recent data accumulation in familial pancreatic cancer (FPC) and hereditary pancreatic cancer is outstanding. Multigene germline panel tests (MGPTs) have revealed that 7%–18% of patients with pancreatic cancer (PC) harbor pathogenic germline variants (PGVs), almost equal to the levels of breast, ovarian, endometrial, and colorectal cancers, with a higher incidence in FPC (14%–26%). The majority of PGVs seen in PC patients are clinically actionable and associated with homologous recombination (HR) pathways (6%–10%, particularly BRCA1/2 in 5%–6%), and the clinical guidelines recommend or propose genetic testing for all PC patients. Consensus guidelines have been established for most of the hereditary syndromes associated with PC risks, and surveillances of the pancreas and other at‐risk organs are recommended for PGV carriers. Hereditary breast and ovarian cancer (HBOC) is the commonest hereditary cancer syndrome that has moderately increasing life‐time risks of PC (3%–7% in Western countries); however, recent Japanese research demonstrated a higher risk level (BRCA1: 16%, BRCA2: 14%). Moreover, recent evidence has suggested a risk linkage between PC and ovarian cancer in HBOC pedigrees. High scores of homologous recombination deficiency suggest biallelic dysfunction of BRCA or other HR‐related genes, and the likely effectiveness of platinum agents and PARP inhibitors against PCs. Remote counseling and testing are possible option in the future genetic medicine. As PC ranks in the second commonest target of precision cancer medicine in Japan, we must treat the patients and manage their at‐risk relatives efficiently.

Navigating Recent Changes in Dosing Information: Dynamics of FDA-Approved Monoclonal Antibodies in Post-Marketing Realities.

Monoclonal antibodies (mAbs) are critical components in the therapeutic landscape, but their dosing strategies often evolve post-approval as new data emerge. This review evaluates post-marketing label changes in dosing information for FDA-approved mAbs from January 2015 to September 2024, with a focus on both initial and extended indications. We systematically analyzed dosing modifications, categorizing them into six predefined groups: Dose increases or decreases, inclusion of new patient populations by body weight or age, shifts from body weight-based dosing to fixed regimens, and adjustments in infusion rates. Among the 86 mAbs evaluated, 21% (n = 18) exhibited changes in dosing information for the initial indication, with a median time to modification of 37.5 months (range: 5-76 months). Furthermore, for mAbs with extended indications (n = 26), 19.2% (n = 5) underwent dosing changes in their first extensions, with a median time to adjustment of 31 months (range: 8-71 months). Key drivers for these adjustments included optimizing therapeutic efficacy, addressing safety concerns, accommodating special populations, and enhancing patient convenience. We also discuss the role of model-informed drug development, real-world evidence, and pharmacogenomics in refining mAb dosing strategies. These insights underscore the importance of ongoing monitoring and data integration in the post-marketing phase, providing a foundation for future precision medicine approaches in mAb therapy.

Genetic subtypes of B-cell acute lymphoblastic leukemia in adults.

B-cell acute lymphoblastic leukemia (B-ALL) is a rare malignancy in adults with outcomes remaining poor, especially compared to children. Over the past two decades, extensive whole-genome studies have identified numerous genetic alterations driving leukemia, leading to the recognition of more than 20 distinct subtypes which are closely associated with treatment response and prognosis. In pediatric B-ALL, large correlation studies have made genetic classification a central component of risk-adapted treatment strategies. Notably, genetic subtypes are unevenly distributed according to age, and the spectrum of genetic alterations and their prognostic relevance in adult B-ALL have been less extensively studied, with treatment primarily based on the presence or absence of BCR::ABL1 fusion. This review provides an overview of genetic subtypes in adult B-ALL, including recent biological and clinical insights in well-established subtypes as well as data on newly recognized subtypes. Their relevance for risk classification, disease monitoring and therapeutic management, including in the context of B-cell-directed therapies, is discussed. This review advocates for continuing efforts to further improve our understanding of the biology of adult B-ALL to establish the foundation of future precision medicine in B-ALL.

Review of Articles Related to the Accident of TEPCO’s Fukushima Daiichi Nuclear Power Station Published in the Japanese Journal of Health Physics: Overview (Secondary Publication)

During the Tokyo Electric Power Company’s Fukushima Daiichi Nuclear Power Station (1F) accident on March 11, 2011, many members of the Japan Health Physics Society, including researchers and radiation workers, were involved in 1F accident-related work. The resulting articles covered a wide range of topics such as lessons learned and future challenges, risk communication, environmental monitoring, dosimetry, radiation medicine, and radioactive waste. In March 2022, a working group was established to review the articles related to the 1F accident published in the Japanese Journal of Health Physics. This article shows the types and number of 1F-related articles published in this journal over a period of about 10 years.

Synthesis of triclosan-derived coumarins as potent, biocompatible, broad-spectrum antimicrobial agents

Objective: Various personal care products previously used triclosan, a chlorinated antimicrobial agent. However, safety and environmental concerns have grown, forbidding its application. Given this fact, the present work aims to repurpose this out-of-use chemical by including it as a precursor for synthesizing nineteen triclosan-based coumarins (TBCs). Methods: The spectrophotometric methods applied to confirm the chemical structures of TBCs were FTIR, 1H-NMR, 13C-NMR, and HRMS. The antimicrobial investigations were run through using broth microdilution methodology and many pathogenic microbes. These include six aerobic and four anaerobic ATCC-approved bacterial strains, as well as two fungal strains. We validated the results by comparing them with three standards: ciprofloxacin, metronidazole, and nystatin, which were based on the tested microbe. On the other hand, the biocompatibility investigations determined the ability of TBCs to inhibit the normal growth of three microbiome strains. Results: The results revealed several conclusive points, including the bactericidal impact of the synthesized TBCs on both pathogenic and microbiome strains tested, with low and high MIC values, respectively. The impact of the synthesized TBCs on pathogenic bacteria was dependent on the number and type of substitutes on the D ring, but this was not the case for microbiome bacteria, where these two factors were of low importance. These factors also influence the activity of the synthesized TBCs against pathogenic fungi. The latter microbes exhibit a high level of sensitivity to the synthetic intermediate, which contains a carboxylic acid moiety within its structure. We concluded from these findings that the number of chlorides that deactivated the D ring directly promoted the anti-aerobic bacterial activity. The same holds true for the anti-anaerobic bacteria, albeit with the addition of nitro groups. Conclusion: the results could provide insights into how the structure of the synthesized TBCs influences their antimicrobial activity. This renders them highly promising as potential future medicines that are robust, safe, and effective against a broad spectrum of microbes.

Path planning for flexible needle based on both insertion mechanism kinematics and needle bending model.

Due to the limited operating space in the magnetic resonance (MR) environment, there is coupled motion in the insertion mechanism, which not only reduces the flexibility of the robot but also challenges the insertion path planning. Meanwhile, the path planning is also restricted by the bending rule of the flexible needle, thus the bending model of the needle is also essentially built. This paper proposes a path planner for the flexible needle based on both the coupled motion kinematics of the insertion robot and the bending model of the flexible needle. A kinematic analysis for the coupled motion of insertion robot is performed. And the bending model of flexible needle is established based on the needle-tissue interactions. The position and posture of the needle insertion at the entry point are obtained by the calculation of the target position and the analysis of the bending model. And the rotation or translation coordinates of each robot joint are calculated by the inverse kinematics of the insertion robot. Then the path planning based on the coupled kinematics and the bending model is realized. The insertion experiments were performed for each target of G1 and G2. The root mean square errors were 0.83 mm and 0.74 mm, and the maximum errors were 1.1 mm and 0.9 mm for G1 and G2, respectively. The experimental results show that the effectiveness and accuracy of the path planning can meet the requirements for a general minimally invasive surgery, so the proposed path planning algorithm is feasible. This study provides a new solution for the path planning of insertion robots for the minimally invasive surgery. This method can meet the insertion mechanism working within the limited operating space in the MR environment and has a high application value in future clinical medicine.

WITHDRAWN: Potential Mechanism and Perspectives of Mesenchymal Stem Cell Therapy for Ischemic Stroke: A Review

Mesenchymal stem cells (MSCs), as a stem cell type with multiple differentiation potentials and immune regulatory abilities, have shown broad prospects in the treatment of ischemic stroke in recent years. The main characteristics of MSCs include their self-renewal ability, differentiation potential for different types of cells, and the ability to secrete various bioactive factors such as cytokines, chemokines, and growth factors, which play a key role in tissue repair and regeneration. In the treatment of ischemic stroke, MSCs exert therapeutic effects through various mechanisms, including promoting vascular regeneration of damaged brain tissue, reducing inflammatory responses, and protecting neurons from damage caused by apoptosis. Researches have shown that MSCs can promote the repair of ischemic areas by releasing neurotrophic factors and angiogenic factors, while inhibiting immune responses triggered by ischemia, thereby improving neurological function. With the in-depth study of its biological mechanism, MSCs have gradually shown good safety and effectiveness in clinical applications. Therefore, fully exploring and utilizing the potential of mesenchymal stem cells in the treatment of ischemic stroke may provide new ideas and solutions for future neural repair and regenerative medicine.

Age-Related Hearing Impairment: Genome and Blood Methylome Data Integration Reveals Candidate Epigenetic Biomarkers.

Age-related hearing impairment (ARHI) is a major planetary health burden that is in need of precision medicine for prevention, diagnosis, and treatment. The present study was set out to identify candidate epigenetic markers for ARHI. Associations of genetically predicted DNA methylation levels with ARHI risk were evaluated using two sets of blood DNA methylation genetic prediction models in 147,997 cases and 575,269 controls of European descent. A total of 1314 CpG sites (CpGs) were significantly associated with ARHI risk at a false discovery rate (FDR) <0.05, including 12 putatively causal CpGs based on fine-mapping analysis. Measured methylation levels of 247 of the associated CpGs were significantly correlated with measured expression levels of 127 nearby genes in blood at an FDR <0.05. A total of 37 CpGs and their 18 nearby genes showed consistent association directions for the methylation-gene expression-ARHI risk pathway. Importantly, three genes (PEX6, TCF19, and SPTBN1) were enriched in auditory disease categories. Our results indicate that specific CpGs may modulate ARHI risk by regulating the expression of candidate ARHI target genes. Future precision medicine and biomarker development research on ARHI are called for.

Biobanking with genetics shapes precision medicine and global health.

Precision medicine provides patients with access to personally tailored treatments based on individual-level data. However, developing personalized therapies requires analyses with substantial statistical power to map genetic and epidemiologic associations that ultimately create models informing clinical decisions. As one solution, biobanks have emerged as large-scale, longitudinal cohort studies with long-term storage of biological specimens and health information, including electronic health records and participant survey responses. By providing access to individual-level data for genotype-phenotype mapping efforts, pharmacogenomic studies, polygenic risk score assessments and rare variant analyses, biobanks support ongoing and future precision medicine research. Notably, due in part to the geographical enrichment of biobanks in Western Europe and North America, European ancestries have become disproportionately over-represented in precision medicine research. Herein, we provide a genetics-focused review of biobanks from around the world that are in pursuit of supporting precision medicine. We discuss the limitations of their designs, ongoing efforts to diversify genomics research and strategies to maximize the benefits of research leveraging biobanks for all.

The Future of Electro-organic Synthesis in Drug Discovery and Early Development.

Electro-organic chemistry presents a promising frontier in drug discovery and early development, facilitating novel reactivity aligned with green chemistry principles. Despite this, electrochemistry is not widely used as a synthesis and manufacturing tool in drug discovery or development. This overview seeks to identify key areas that require additional research to make synthetic electrochemistry more accessible to chemists in drug discovery and early development and provide potential solutions. This includes expanding the reaction scope, simplifying rapid scale-up, developing electrode materials, and improving knowledge transfer to aid reproducibility and increase the awareness of electrochemistry. The integration of electro-organic synthesis into drug discovery and development holds the potential to enable efficient, sustainable routes toward future medicines faster than ever.

Progress in immune-targeted combination therapy for melanoma

Abstract. Melanoma is a type of skin cancerous tumor that develops from melanocytes and often appears on the skin's surface, however it can also spread to other areas like the eyes and mucous membranes. Research on it has made significant progress in recent years. Immunotherapy has become an important means of treating melanoma. The use of anti-CTLA-4 and anti-PD-1/PD-L1 antibodies has achieved significant success, so some patients have achieved long-term survival. benefit. Secondly, there have been breakthroughs in targeted therapeutic drugs targeting specific molecular targets such as BRAF and MEK. It has the ability to successfully stop melanoma cells from growing and spreading. Despite significant advances in immunotherapy and targeted therapies, drug resistance remains a serious problem; metastasis of melanoma is one of the main causes of its lethality, but little is known about how melanoma cells metastasize to other organs There are still many unanswered questions about the mechanism. This article compares the benefits of immune-targeted combination therapy with immunotherapy alone. It also immunotherapy and targeted therapy alone. It comes to the conclusion that combination therapy is the best course of action. The mechanism of action, effectiveness and drawbacks of drug resistance of the targeted therapy drug Vemurafenib were also introduced, further confirming the 1+1&gt;2 treatment plan. Combination therapy provides new ideas for future cancer medicine, but the drug resistance of some targets needs to be solved, and subsequent research can focus on the development of new targets.

Synthesis and Anti-Inflammatory and Analgesic Potentials of Ethyl 2-(2,5-Dioxo-1-Phenylpyrrolidin-3-yl)-2-Methylpropanoate.

Background/Objectives: Inflammation and analgesia are two prominent symptoms and often lead to chronic medical conditions. To control inflammation and analgesia, many marketed drugs are in practice but the majority of them have severe side effects. Methods: This study involved the synthesis of a pivalate-based Michael product and evaluated it for in vitro COX-1, COX-2, and 5-LOX inhibitory potentials using specific assays. Molecular docking studies were also assessed. Based on the in vitro results, the compound was also subjected to in vivo anti-inflammatory and antinociceptive studies. Results: The pivalate-based Michael product (MAK01) was synthesized by an organocatalytic asymmetric Michael addition of ethyl isobutyrate to N-phenylmaleimide with an isolated yield of 96%. The structure of the compound was confirmed through 1H and 13C NMR analyses. The observed IC50 values for COX-1, COX-2, and 5-LOX were 314, 130, and 105 μg/mL, respectively. The molecular docking studies on the synthesized compound showed binding interactions with the minimized pockets of the respective enzymes. In a carrageenan model, a percent reduction in edema when administered at 10 mg/kg (a reduction of 33.3 ± 0.77% at the second hour), 20 mg/kg (a reduction of 34.7 ± 0.74% at the second hour), and 30 mg/kg (a reduction of 40.58% ± 0.84% after the fifth hour) was observed. The compound showed a significant response at concentrations of 50, 100, and 150 mg/kg with latency times of 10.32 ± 0.82, 12.16 ± 0.51, and 12.93 ± 0.45 s, respectively. Conclusion: In this study, we synthesized a pivalate-based Michael product for the first time. Moreover, based on its rationality and potency, it was found to be an effective future medicine for the management of analgesia and inflammation.

3D keloid spheroid model: Development and application for personalized drug response prediction

Research on keloid is limited by the lack of proper in vitro and animal model reflecting in vivo status. Based on heterogeneity of keloid and important role of endothelial cells in its pathogenesis, a novel 3D in vitro keloid spheroid prepared with keloid fibroblasts and endothelial cells was evaluated in this study. Commercial cell lines of keloid fibroblasts and endothelial cells were used at various cellular ratios to generate keloid spheroids to determine the optimal condition. Keloid spheroids from three keloid patients were also made and their usefulness as in vitro models, including their responses to drugs, were assessed. Spheroids with higher endothelial cell proportions exhibited increased viability and propagation ability. Patient-derived keloid spheroids showed heterogeneity which might reflect individual clinical conditions. The optimal ratio of fibroblasts to endothelial cells was determined to be 4:1 for keloid spheroids based on gene expression and viability analyses. Patient-derived keloid spheroid showed better keloidal changes in genetic expressions than 2D monolayer culture. Spheroids exhibited varied responses and resistance to each drug used for keloids, depending on the cell type used. 3D keloid spheroids might provide an effective in vitro model for investigating disease pathogenesis and appropriate treatment modalities for future precision medicine.

Naringenin can Inhibit the Pyroptosis of Osteoblasts by Activating the Nrf2/HO-1 Signaling Pathway and Alleviate the Differentiation Disorder of Osteoblasts Caused by Microgravity.

Naringenin (4,5,7-trihydroxyflavone, NAR) is an effective active ingredient in Rhizoma Drynariae, which has many biological functions, encompassing anti-inflammatory and -oxidant functions. Prior research has shown that NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasomes possessed a significant contribution to osteoporosis. However, the NAR impact on bone loss caused by microgravity remains unclear. Classical microgravity simulation methods were used to induce simulated microgravity (SMG) in mice and cells. Microcomputed tomography, immunohistochemical examination, and hematoxylin and eosin staining were implemented to ascertain alterations in bone microstructure and morphology in mice subsequent to NAR gavage. Cellular investigations were implemented encompassing quantitative real-time polymerase chain reaction, Western blotting, and immunofluorescence labeling to investigate the molecular mechanism behind NAR resistance to microgravity-induced bone loss. Our research has shown that NAR can significantly enhance the SMG-stimulated alterations in bone microstructure and morphology in mice, mainly by increasing the trabecular thickness, bone volume fraction, and trabecular number while increasing the bone trabecula number. Cell experiments also showed that SMG caused the activation of inflammatory corpuscles of NLRP3 and induced pyroptosis simultaneously, which can be confirmed by the upregulation of protein and mRNA expression levels such as those of NLRP3, cleaved caspase-1, gasdermin D, and apoptosis-associated speck-like protein. The occurrence of pyroptosis further led to the disorder of osteogenic differentiation, which showed that the osteopontin, Runt-related transcription factor 2, bone morphogenetic protein 2, and alkaline phosphatase expression levels were decreased. The intervention of NAR can activate the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway, reverse this phenomenon via controlling the reactive oxygen species generation in cells and correcting mitochondrial malfunction, weaken the pyroptosis of osteoblasts (OBs), and promote osteogenic differentiation. In summary, NAR could hinder the pyroptosis of OBs caused by SMG and promote osteogenic differentiation via activating the Nrf2/HO-1 pathway. This provides a unique view for inhibiting bone loss under weightlessness and confirms the NAR capacity in treating microgravity-stimulated bone loss, giving new ideas and methods for future space medicine development.

The Potential Role of Artificial Intelligence in Emergency Medicine and Medical Education

Artificial intelligence (AI) is increasingly recognized for its transformative potential in healthcare, particularly in emergency medicine. The fast-paced, highstakes nature of emergency departments (EDs) demands rapid decision-making, often under significant time and resource constraints. AI-driven solutions have already demonstrated their ability to enhance diagnostic accuracy, improve triage processes, and optimize resource allocation in emergency settings. However, AI’s potential extends beyond clinical practice into the realm of medical education, where large language models (LLMs) may offer novel opportunities for training future emergency medicine professionals.

Preserving Stem Cells for Potential Use in Future Reparative Medicine

With its enormous potential for regenerative medicine and therapeutic applications, stem cell preservation represents a major breakthrough in biomedical science. Stem cells are gathered, processed, and stored under carefully monitored circumstances in order to preserve their viability for potential use in the future. Because they may differentiate into a variety of cell types, stem cells—especially those derived from sources like umbilical cord blood—are essential for both therapeutic and research uses. An essential function of cord blood banking is to offer a plentiful supply of immune system cells that may be stored for potential future therapeutic applications. Immunological deficits, osteoarthritis, Parkinson's disease, and heart failure are just a few of the conditions for which stem cell treatments have shown promise. Notwithstanding the promise, there remain obstacles such immunological rejection and the need for more research to fully comprehend the development and functionality of stem cells. It is essential for the general public to be informed about stem cell treatments and cord blood banking in order for expectant parents to make well-informed decisions. Future advancements in the subject depend heavily on resolving ethical issues and enhancing the effectiveness of stem cell-based therapies. To fully realise the promise of stem cell preservation in conventional medicine, more research, creativity, and international cooperation are required.

A novel approach ofdifferentiation of adenoma and carcinoma in lung cancer based on biogenic in situ synthesis of gold nanostructures on various oligonucleotide motifs.

Aunique approach is introducedfor constructing gold nanocrystals (AuNCs) with RNA motif-directed morphologies in a sequence-independent manner and itsapplications in theclinical areaare described. By using this method, a label-free LSPR-based detection method for the SOX2OT transcript, long non-coding RNAs (lncRNAs), which is a prognostic indicator of poor survival in lung cancer patientsis presented. For the first time, we examined how the structural changes of RNA after the heteroduplex formation with a specific DNA probe can change the morphology and LSPR band of AuNCs. Using this method, is was possible to differentiate lung squamous cell carcinoma from adenocarcinoma samples without a need for a prior amplification of the target lncRNA. The approach of using specific DNA probe enables the in situ synthesis of nanocrystals in a different way and expands this method for future translational medicine, particularly detection of specific RNA.

HLA-B allele frequencies and implications for pharmacogenetics in the Kuwaiti population.

We utilized the HLA-HD tool to extract, annotate, and analyse HLA-B alleles from the exome data of 561 Kuwaiti individuals, sequenced on the Illumina HiSeq platform. HLA typing was conducted using the HLA-HD tool with a reference panel from the IPD-IMGT/HLA database. The major HLA-B pharmacogenetic markers were obtained from the HLA Adverse Drug Reaction Database, focusing on alleles with significant ADR associations in published literature. The distribution of HLA-B alleles in the Kuwaiti population revealed that the most frequent alleles were HLA-B*50:01 (10.52%), HLA-B*51:01 (9.89%), HLA-B*08:01 (6.06%), HLA-B*52:01 (4.55%), HLA-B*18:01 (3.92%), and HLA-B*41:01 (3.65%). Notably, alleles HLA-B*13:01, HLA-B*13:02, HLA-B*15:02, HLA-B*15:13, HLA-B*35:02, HLA-B*35:05, HLA-B*38:01, HLA-B*40:02, HLA-B*44:03, HLA-B*51:01, HLA-B*57:01 and HLA-B*58:01 were identified with known associations to various ADRs. For example, HLA-B*51:01 was associated with clindamycin, phenobarbital, and phenytoin, and was found in 18% of individuals. Our study enriches the regional genetic landscape by delineating HLA-B allele variations within Kuwait and across the Arabian Peninsula. This genetic insight, along with the identification of markers previously linked to drug hypersensitivity, provides a foundation for future pharmacogenetic research and potential personalized medicine strategies in the region.

B-185 A Comparison Between Two Oral Sample Collection Devices on Preserving High-Quality Genomic DNA

Abstract Background High-quality genomic testing significantly enhances the knowledge on gene-disease association, and greatly benefits future biomedical research and precision medicine. However, widely used saliva sample collection presents challenges with high-quality and quantity of human DNA and high bacterial DNA ratio. In this study, we validated the performance of two commercially available oral collection devices for their ability to preserve high-quality genomic DNA long-term at room temperature. Methods Fifty-one buccal samples in total from twelve donors were collected using two kinds of commercially available oral sample collection devices (iSWAB®-DNA (Device 1) and OCD-100 (Device 2)). All of the collected samples were stored at ambient temperature for up to 1 year. Collected samples were extracted with QIAamp Blood Mini Kit (Qiagen) at baseline, 30 days, 60 days, and 1 year. All DNA yields were measured using a Nanodrop One Microvolume UV-Vis Spectrophotometer; TapeStation System was used for determining the integrity of DNA. The bacterial DNA ratio was estimated by quantitative PCR with primers targeting the 16S rRNA gene known to be present in prokaryotes but not eukaryotes. Results Device 1 had higher yield (Device 1: 18.59 ± 8.98; Device 2: 6.44 ± 4.62), lower bacterial DNA ratio (Device 1: 2.06 ± 1.93; Device 2: 3.79 ± 4.58), and higher overall DNA integrity (Device 1: 6.1 ± 0.31; Device 2: 5.42 ± 0.96) compared to Device 2. Device 1 demonstrated longer post-collection sample stability at ambient temperature compared with Device 2 regarding DNA yield, bacterial DNA ratio and DNA integrity. No significant changes in DNA yield, integrity, and bacterial DNA ratio were observed after one year of storage in Device 1. No significant changes in DNA yield, integrity, and bacterial DNA ratio were observed after 60 days of storage in Device 2. However, Device 2 showed a significant increase in DNA yield, bacterial DNA ratio, and DNA integrity comparing baseline to 1 year. Conclusions Device 1 preserves higher quantity and quality of DNA from oral samples at ambient temperature for up to 1 year. These advantages significantly enhance efficiency and cost-effectiveness in downstream applications such as genotyping and sequencing, making it a valuable tool in genomics research with a commendable success rate.

Mechanism of Yi-Qi-Bu-Shen Recipe for the Treatment of Diabetic Nephropathy Complicated with Cognitive Dysfunction Based on Network Pharmacology and Experimental Validation.

Diabetic nephropathy (DN) and cognitive dysfunction (CD) are common complications of diabetes. Yi-Qi-Bu-Shen Recipe (YQBS) can effectively reduce blood glucose, improve insulin resistance, and delay the progression of diabetic complications. The underlying mechanisms of its effects need to be further studied. This study elucidates the mechanism of YQBS in DN with CD through network pharmacology and experimental validation. Protein-protein interaction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Male Sprague-Dawley (SD) rats were divided into 6 groups: model, YQBS (2, 4, 8 g/kg), positive control (metformin, 200 mg/kg), and control; the DN model was established by high sugar and high fat diet combined with intraperitoneal streptozotocin injection. After the DN model was established, the rats were gavaged for 10weeks. Serum, kidneys, and hippocampus tissues were collected to measure the expression levels of TLR4, NF-κB, TNF-α, and IL-6. The network pharmacology analysis showed that quercetin and kaempferol were the main active components of YQBS. TNF and IL-6 were the key targets, and TLR4/NF-κB pathway was crucial to YQBS in treating DN complicated with CD. Experimental validation showed that the intervention of YQBS can reduce TNF-α and IL-6 in serum, and also significantly decreases the protein expression of TLR4 and NF-κB. YQBS exerts anti-inflammatory effects on DN with CD through TLR4/NF-κB pathway. This study provides a biological basis for the scientific usage of YQBS in inflammation diseases and supplies experimental evidence for future traditional Chinese medicine development.