Drug Discoveries & Therapeutics

Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder characterized by a complex pathogenesis and limited treatment options. Yishen Huatan and Huoxue decoction (YHHD), as a traditional Chinese Medicine formula, has shown effectiveness in treating PCOS. However, the specific mechanisms by which YHHD exerts its therapeutic effects remain unclear. In this study, we performed to investigate the therapeutic effects of YHHD and quercetin on dehydroepiandrosterone-induced PCOS mice, and examine the effect of quercetin on the decidualization of T-HESCs under hyperinsulinemic conditions...

Limited studies are associated with premature ovarian insufficiency (POI)-related osteoimmune disorder currently. Bu-Shen-Ning-Xin decoction (BSNXD) displayed a favorable role in treating postmenopausal osteoporosis. However, its impact on the POI-related osteoimmune disorder remains unclear. The study primarily utilized animal experiments and network pharmacology to investigate the effects and underlying mechanisms of BSNXD on the POI-related osteoimmune disorder. First, a 4-vinylcyclohexene dioxide (VCD)-induced POI murine model was conducted to explore the therapeutical action of BSNXD...

Tuberculosis is a chronic infectious disease caused by mycobacterium tuberculosis infection. In the world, tuberculosis is an important factor affecting women's reproductive health, which can cause reproductive tract anatomy abnormalities, embryo implantation obstacles, ovarian reserve and ovulation dysfunction, leading to female infertility. This group of women usually need to seek assisted reproductive technology to conceive. Latent tuberculosis infection during pregnancy has no clinical manifestation, but may develop into active tuberculosis, leading to adverse pregnancy outcomes...

Previous reports proposed the concept and criteria of epidermotropic metastatic malignant melanoma (EMMM): (a) dermal involvement equal to or broader than the epidermal involvement, (b) atypical melanocytes within the dermis, (c) thinning of the epidermis, (d) widening of the papillary dermis with an epithelial collarette, and (e) vascular invasion of atypical melanocytes. However, it remains unclear whether EMMM also involves the mucosal epithelium. In this case, the patient was diagnosed with EMMM based on the histopathological findings of the patient's multiple skin lesions and clinical course...

Both PAK1 (RAC/CDC42-activating kinase 1) and TOR (Target of Rapamycin) are among the major oncogenic/ageing kinases. However, they play the opposite role in our immune system, namely immune system is suppressed by PAK1, while it requires TOR. Thus, PAK1-blockers, would be more effective for therapy of cancers, than TOR-blockers. Since 2015 when we discovered genetically that PDGF-induced melanogenesis depends on "PAK1", we are able to screening a series of PAK1-blockers as melanogenesis-inhibitors which could eventually promote longevity...

We have established several models of infectious diseases in silkworms to explore disease-causing mechanisms and identify new antimicrobial substances. These models involve injecting laboratory-cultured pathogens into silkworms and monitoring their survival over a period of days. The use of silkworms is advantageous because they are cost-effective and raise fewer ethical concerns than mammalian subjects, allowing for larger experimental group sizes. To capitalize on these benefits, there is a growing importance in mechanizing and automating the experimental processes that currently require manual labor...

The shift towards community-based care in Japan has led to increased medication assistance for older people by non-medical care staff. These staff members help take pre-packaged medications, apply patches, and administer eye drops. This study assessed the risks associated with such assistance by reviewing medication-related incidents across 106 residential care facilities between April 1, 2015, and March 31, 2016. An analysis of incident reports showed that all incidents were minor, with no serious outcomes...

Endometriosis (EM), also known as Zhengjia in traditional Chinese medicine, is a common disease that significantly impacts women's health. An integrated treatment approach combining traditional Chinese medicine (TCM) and western medicine has demonstrated significant clinical efficacy in the management of this condition. Specifically, it has been effective in addressing blood circulation and other diseases. MicroRNAs (miRNAs), which are molecules important in gene regulation, have been implicated in various physiologic and pathologic processes...

The continuous evolution of SARS-CoV-2 variants constitutes a significant impediment to the public health. The World Health Organization (WHO) has designated the SARS-CoV-2 variant JN.1, which has evolved from its progenitor BA.2.86, as a Variant of Interest (VOI) in light of its enhanced immune evasion and transmissibility. The proliferating dissemination of JN.1 globally accentuates its competitive superiority and the potential to instigate fresh surges of infection, notably among cohorts previously infected by antecedent variants...

In Japan, the switch from branded to generic infusion fluids has been promoted as a national policy. Recently, as generic products have been in short supply, the switch from generic to branded infusion fluids has increased. However, certain additives for injectable infusion fluids, such as nonvolatile acids like acetic acid and hydrochloric acid, are not required to be listed in the package insert. We hypothesized that the addition of nonvolatile acids may be one of the reasons for the differences in physicochemical properties between the branded and generic infusion fluids...

Maintenance of pregnancy is highly dependent on the maternal immune system. High levels of regulatory T cells (Tregs) accumulate in the maternal placenta to suppress immunoreactivity against fetal antigens. We assessed whether Astragalus root (AsR) and AsR-containing Kampo medicines modulate immunoreactivity and thereby increase mouse litter size. AsR-exposed murine splenocytes exhibited significantly increased IL-2 secretion. In AsR-exposed mice, total Tregs were significantly increased, whereas cytotoxic T lymphocyte antigen 4 (CTLA-4)-positive Tregs were decreased in AsR-exposed mice...

To get a thorough understanding of PD-1/L1 inhibitor-related hypophysitis (PD-1/L1-irH), we utilized a combination of disproportionality analysis and case analysis to comprehensively characterize the clinical features of PD-1/L1-irH. Significant signals of hypophysitis were detected for all PD-1/PD-L1 inhibitors in the FAERS (FDA Adverse Event Reporting System). As revealed by both FAERS and the case analysis, PD-1/L1-irH occurred more commonly in males, PD-1 inhibitors users and patients older than 65 years...

The eight flavonoids, apigenin, chrysin, hesperidin, kaempferol, myricetin, quercetin, rutin and luteolin were tested for the inhibition of human parainfluenza virus type 2 (hPIV-2) replication. Three flavonoids out of the eight, kaempferol, quercetin and luteolin inhibited hPIV-2 replication. Kaempferol reduced the virus release (below 1/10,000), partly inhibited genome and mRNA syntheses, but protein synthesis was observed. It partly inhibited virus entry into the cells and virus spreading, and also partly disrupted microtubules and actin microfilaments, indicating that the virus release inhibition was partly caused by the disruption of cytoskeleton...

Exertional heatstroke (EHS), a severe form of exertional heat illness (EHI), is the third leading cause of death in athletes; thus, early detection and prevention of EHI can help prevent EHS, which is a life-threatening condition. This study aimed to clarify the association between the cognizance of experiencing EHI and living conditions and specific EHI symptoms among collegiate athletes. This study was conducted in October 2022 by administering a questionnaire to 237 male collegiate athletes. Of the 215 (90...

Papillary thyroid carcinoma (PTC), the most common endocrine tumor, often spreads to cervical lymph nodes metastasis (CLNM). Preoperative diagnosis of CLNM is important when selecting surgical strategies. Therefore, we aimed to explore the effectiveness of quantitative parameters of contrast-enhanced ultrasound (CEUS) in predicting CLNM in PTC. We retrospectively analyzed 193 patients with PTC undergoing conventional ultrasound (CUS) and CEUS. The CUS features and quantitative parameters of CEUS were evaluated according to PTC size ≤ 10 or > 10 mm, using pathology as the gold standard...

A fluorescence immunochromatography (FIC) kit was developed recently using fluorescent silica nanoparticles coated with a recombinant C-terminal fragment of the surface lectin intermediate subunit (C-Igl) of Entamoeba histolytica to establish rapid serodiagnosis of amebiasis. We further evaluated the system using serum samples from 52 Thai patients with amebiasis. Of the patients, 50 (96%) tested positive using FIC. The samples were also tested using enzyme-linked immunosorbent assay (ELISA) with C-Igl as the antigen...

The altered behaviors and functions of pelvic floor fibroblasts are pathophysiological changes of pelvic organ prolapse (POP). Our previous study showed that advanced glycated end products (AGEs) accumulated in the pelvic tissues of POP and induced fibroblast apoptosis. The study was designed to investigate whether quercetin antagonize AGEs-induced apoptosis and functional inhibition of fibroblasts. The uptake of 5-ethynyl-2'-deoxyuridine (EdU) was evaluated for cell proliferation. Flow cytometric analysis was applied for cell apoptosis...

Aortic aneurysm and aortic dissection (AAD) are severe life-threatening cardiovascular disorders for which no approved pharmaceutical therapies are currently available. Protein S-nitrosylation (SNO) is a typical redox-dependent posttranslational modification whose role in AAD has yet to be described. Recently, Zhang et al. revealed for the first time that SNO modification of macrophage cytoskeletal protein septin2 promotes vascular inflammation and extracellular matrix degradation in aortic aneurysm. Mechanically, the TIAM1-RAC1(T lymphoma invasion and metastasis-inducing protein 1-Ras-related C3 botulinum toxin substrate 1) axis participates in the progression of AAD induced with S-nitrosylated septin2...

Senolytics are drugs that specifically target senescent cells. Flavonoids such as quercetin and fisetin possess selective senolytic activities. This study aims to investigate if chalcones exhibit anti-senescence activities. Anti-senescence effect of 11 chalcone derivatives on the replicative senescence human aortic endothelial cells (HAEC) and human fetal lung fibroblasts (IMR90) was evaluated. Compound 2 (4-methoxychalcone) and compound 4 (4-bromo-4'-methoxychalcone) demonstrated increased cytotoxicity in senescent HAEC compared to young HAEC, with significant differences on IC50 values...

Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting fertility and mental health among women of reproductive age. In addition to anovulation and hyperandrogenism, patients also experience metabolic issues, such as insulin resistance, obesity, and dyslipidemia, as well as chronic low-grade inflammation throughout the body. Recent studies have shown that even with assisted reproductive technology to treat anovulatory issues, patients with PCOS still have higher rates of adverse pregnancy outcomes and abortion compared to normal pregnancies...