Menopausal symptoms primarily result from ovarian dysfunction and declining estrogen levels, leading to multisystem disorders. Although hormone therapy remains the most effective treatment, its long-term use is associated with significant risks, prompting interest in alternative options. Kampo medicine, a traditional Japanese system derived from Chinese herbal medicine, has gained renewed attention as a complementary and personalized therapeutic approach to menopausal health. This review aims to systematically summarize the current application and clinical evidence of Kampo medicine in the management of menopausal symptoms across multiple domains, including vasomotor, neuropsychiatric, musculoskeletal, skeletal, and genitourinary systems. Furthermore, the review seeks to further validate its efficacy through the mechanistic actions of its key ingredients. While the therapeutic effects of Kampo medicine on hot flashes have been inconsistent, it has demonstrated significant efficacy in improving emotional disturbances, sleep disorders, and somatic symptoms, particularly among individuals whose conditions are not driven solely by hormonal imbalances. In the management of osteoporosis, the integration of Kampo medicine with conventional Western treatments not only enhances overall therapeutic outcomes but also contributes to the reduction of adverse effects. One limitation of current research is the lack of randomized controlled trials (RCTs) evaluating the efficacy of Kampo medicine in managing Genitourinary Syndrome of Menopause (GSM), highlighting the need for further investigation in this area. The integration of Kampo medicine into menopausal symptom management may contribute to a more holistic, patient-centered approach that offers both traditional and Western medical options. This integrative model has the potential to support shared decision-making and improve personalized care for menopausal women.

In recent years, there has been an escalating incidence of recurrent pregnancy loss (RPL), imposing substantial psychosocial and economic burdens on families. Despite extensive investigations, approximately 50% of cases remain idiopathic, underscoring the intricate nature of potential pathogenic mechanisms. Quercetin (QUE), a prevalent flavonoid compound, exhibits potential in the therapeutic modulation of RPL by influencing endocrine, coagulation, oxidative stress, inflammation, and immune responses. This review aims to elucidate the potential role of QUE in RPL, explore its molecular mechanisms, and delineate its therapeutic significance. Herein, we synthesize existing evidence on the impact of QUE in RPL, particularly in traditional Chinese medicine, accentuating areas necessitating further exploration. QUE demonstrates regulatory prowess over RPL by modulating endocrine functions, encompassing thyroid functionality, diabetes, polycystic ovary syndrome, and luteal phase defects. It exhibits anti-inflammatory and antioxidant properties, influences coagulation functions, and affects immune cells such as T cells, T helper cells, macrophages, and natural killer cells. QUE also interacts with maternal-fetal interface cells, including myeloid-derived suppressor cells, stromal cells, and extravillous trophoblast cells, highlighting its multifaceted role in the modulation of RPL. Despite promising preclinical data, clinical trials directly targeting RPL remain limited. We emphasize the need for rigorous human studies to validate QUE's efficacy and safety in pregnancy. By elucidating the mechanistic underpinnings of QUE in treating RPL, this research may contribute to developing targeted interventions for RPL and other adverse pregnancy conditions, ultimately ameliorating reproductive health and well-being for affected individuals and families.

Biologics are essential for managing immune-related inflammatory diseases during pregnancy to prevent disease progression and adverse pregnancy outcomes. However, data on the safety of biologics in a broader population are limited. This study aims to evaluate abortion-related adverse events (AEs) associated with adalimumab, etanercept, ustekinumab, and dupilumab, using data from the FDA Adverse Event Reporting System (FAERS) database. A disproportionality analysis was performed using the Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) to identify signals of abortion-related AEs. The time-to-onset profiles were assessed by analyzing the description and Weibull shape parameters (WSPs) for these events. Sensitivity analyses were also conducted, including drug–drug interaction studies, logistic regression, and a similar retrospective analysis using data from the Japanese Adverse Drug Event Report (JADER) database. Disproportionality analysis revealed specific signals for abortion-related AEs associated with adalimumab, etanercept, and ustekinumab. The drug–drug interaction analysis indicated that these biologics, particularly without methotrexate or prednisolone, increase the risk of abortion-related AEs. Logistic regression identified several factors influencing outcomes. The time-to-onset analysis revealed that dupilumab had an earlier onset of 62.5 days, while etanercept had a later onset at 184 days. WSPs analysis revealed that signals for adalimumab, ustekinumab, and dupilumab exhibited early failure-type features, indicating a decreasing risk of abortion-related AEs over time. In conclusion, adalimumab, etanercept, and ustekinumab are associated with an increased risk of abortion-related adverse pregnancy outcomes, though the signals remain relatively weak. Further large-scale studies are needed to provide more definitive evidence.

Phosphate functionalization of nanogels (NGs), originally designed to enhance interactions with fungal pathogens, also significantly influences their immune interactions and systemic behaviour. In this study, we investigated how phosphate-modified NGs perform as antifungal carriers in vivo using the silkworm model. We found that phosphate functionalization promotes faster internalization by granulocytes—immune cells functionally similar to mammalian neutrophils—highlighting a trade-off between antifungal activity and immune uptake. In parallel, phosphate-functionalized NGs exhibited prolonged circulation, more consistent biodistribution patterns, and reduced batch variability compared to unmodified NGs. These features contributed to superior and more reproducible in vivo antifungal efficacy when delivering itraconazole. Importantly, the biodistribution profiles observed in silkworms aligned well with previous mammalian data, further validating silkworms as an efficient, cost-effective model for early-stage evaluation of nanocarrier systems. Our findings underscore the importance of tuning surface functionalization to balance immune interaction and therapeutic performance, providing valuable insights for optimizing systemic antifungal nanotherapies.

The human body is constantly exposed to light from the environment, and intense light is a source of skin inflammation. Although cellular responses to high-energy ultraviolet light have long been reported, the photoresponsive mechanism occurring after skin exposure to visible light remains unclear. This study focused on mast cells involved in inflammation and examined the expression of photoreceptors and their effects on degranulation in mast cells. Photoreceptors expressed in two mast cell cultures (P-815 and RBL-2H3) were examined by RT-PCR and western blotting to demonstrate that OPN3 was expressed in RBL-2H3 cells. Next, the effect of visible light exposure on degranulation was evaluated by measuring β-hexosaminidase activity in the culture medium. The results show that β-hexosaminidase release was most strongly induced at wavelengths of ~460 nm, which corresponds to the absorption peak of OPN3. In addition, suppression of OPN3 expression by siRNA reduced β-hexosaminidase release at 460 nm. These results suggest that OPN3 expressed in mast cells mediates degranulation in skin inflammation that occurs upon exposure to intense light.

The papain-like protease (PLpro), a cysteine protease found in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), plays a crucial role in viral replication by cleaving the viral polyproteins and interfering with the host's innate immune response through deubiquitination and deISGylation activities. Consequently, targeting PLpro has emerged as an appealing therapeutic strategy against SARS-CoV-2 infection. Despite considerable efforts in the development of PLpro inhibitors, there is currently no drug available on the market that specifically targets PLpro. Improving drug screening strategies and identifying additional candidate compounds could significantly contribute to the advancement of antiviral agents targeting PLpro. To address this pressing issue, our present study has developed a highly efficient compound screening strategy based on a supervised machine learning approach. Integrated with further molecular simulation approaches such as molecular docking, molecular dynamics simulations, and quantum chemical calculations, we have identified seven compounds with potent inhibitory activity against PLpro. Notably, two of these compounds exhibited superior activity compared to Jun12682, which is currently considered the best-performing inhibitor against PLpro. Furthermore, some crucial residues in SARS-CoV-2 PLpro were recognized as favorable contributors to the binding with inhibitor, which would provide valuable insights for the development of more potent and highly selective SARS-CoV-2 PLpro inhibitors. The compound screening strategy and potential PLpro inhibitor candidates revealed in the present study would hold promise for advancing the development of antiviral drugs targeting SARS-CoV-2 and its variants.

Chronic inflammation in the colon has been recognized as a key pathogenic mechanism driving colorectal cancer development. TRPA1 (transient receptor potential ankyrin 1), a key member of the TRP cation channel superfamily, is closely implicated in inflammatory processes and has emerged as a promising therapeutic target for anti-inflammatory drug development. However, the precise role of TRPA1 in colorectal carcinogenesis and its potential as a therapeutic target for colorectal cancer (CRC) remain incompletely understood. In this study, we demonstrate that Trpa1 knockout significantly exacerbates DSS-induced colitis-associated tumorigenesis in murine models, a phenomenon mechanistically linked to Trpa1 deficiency-mediated aggravation of inflammatory bowel pathology. RNAseq and gene knockout effect analysis revealed a consistently low expression pattern of TRPA1 across colorectal cancer cell lines (n = 58, median log2(TPM+1) = 0.025), with limited impact on cell viability upon TRPA1 knockout. Notably, analysis of human clinical specimens revealed substantial downregulation of TRPA1 expression in CRC compared to adjacent normal tissues. Kaplan-Meier survival analysis further indicated that patients with TRPA1-low tumors exhibited significantly poorer overall survival outcomes. These collective data suggest a tumor-suppressive role for TRPA1 in colorectal carcinogenesis, potentially through its immunomodulatory functions within the colitis-cancer transformation axis.

As the most prevalent form of dementia, Alzheimer's disease (AD) represents a major public health challenge. Early diagnosis is crucial to delaying disease progression, and yet the gold standard for detection of biomarkers — cerebral positron emission tomography (PET) imaging and cerebrospinal fluid biomarker analysis — is constrained by invasiveness, high costs, and limited accessibility. On May 16, 2025, the FDA granted its first clearance to the Lumipulse G blood test, which utilizes the plasma pTau217/Aβ_1-42 ratio, for the diagnosis of amyloid plaques in symptomatic patients age 55 or older. In clinical validation, concordance rates with amyloid PET brain scans/the results of cerebrospinal fluid biomarker detection were 91.7% (positive) and 97.3% (negative). Similar blood-based assays have previously been approved in Japan (HISCL™ Aβ_42/40), the United Kingdom (PrecivityAD2™), and China. While concerns regarding false-positive/false-negative rates necessitate continued attention and their role as adjunctive diagnostic tools requires integration with comprehensive clinical assessment and other tests, the rapid development and regulatory clearance of these blood-based biomarker assays undeniably offer promising prospects for transforming the diagnostic and therapeutic paradigm for AD.

Dry eye disease (DED) is a common ocular surface disorder that markedly affects the quality of life (QoL) of patients. Conventional treatments for DED were unable to meet current medical needs. Acoltremon, a transient receptor potential melastatin 8 (TRPM8) agonist, was first approved by the US Food and Drug Administration on May 28, 2025 for treatment of the signs and symptoms of DED. Acoltremon activates TRPM8 receptors, thereby increasing tear production and providing a cooling sensation for symptom relief. Results of clinical trials demonstrated that 0.003% acoltremon markedly alleviated signs and symptoms of DED. Adverse events associated with acoltremon were primarily instillation site pain, and no serious ocular adverse events were noted. Acoltremon has multiple advantages: rapid onset of action, significant alleviation of dry eye signs and symptoms, and favorable safety and tolerability. In summary, the approval of acoltremon represents a new therapeutic perspective on the management of DED.

A deficiency in DNA mismatch repair (MMR) leads to microsatellite instability (MSI), which is associated with a favorable response to immune checkpoint inhibitors (ICIs), and the Promega MSI Analysis System is approved as a companion diagnostic tool for it. In this study, we investigated the MMR status in patients with primary cutaneous lymphoma (PCL) diagnosed at our hospital. MSI was found in 1 of the 29 patients (3.4%), an 87-year-old man diagnosed with subcutaneous panniculitis-like T-cell lymphoma. Only the NR‐21 marker was present in both tumor and normal tissue, indicating that the MMR status was MSI-low, and he had a germline mutation of SLC7A8. Our study showed that most PCLs are microsatellite stable tumors. This study is a single-center small-sample investigation and requires validation in larger cohorts.