Triple-negative breast cancer (TNBC) is a unique breast cancer subtype characterized by a lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. Since TNBC lacks ER, PR, and HER2, there are currently no drugs that specifically target TNBC. Therefore, the development of new drugs or effective treatment strategies to target TNBC has become an urgent clinical need. Research has shown that the application of histone deacetylase (HDAC) inhibitors and DNA methyltransferase (DNMT) inhibitors leads to genomic and epigenomic instability. This, in turn, triggers the activation of pattern recognition receptors (PRRs) and subsequently activates downstream interferon (IFN) signalling pathways. In this study, the bifunctional HDAC and DNMT inhibitor J208 exhibited antitumour activity in TNBC cell lines. J208 effectively induced apoptosis and cell cycle arrest at the G0/G1 phase, inhibiting cell migration and invasion in TNBC. Moreover, this bifunctional inhibitor induced the expression of endogenous retroviruses (ERVs) and elicited a viral mimicry response, which increased the intracellular levels of double-stranded RNA (dsRNA) to activate the innate immune signalling pathway in TNBC. In summary, we demonstrated that the bifunctional inhibitor J208, which is designed to inhibit HDAC and DNMT, has potent anticancer effects, providing a new research basis for reactivating antitumour immunity by triggering innate immune signalling and offering a promising strategy for TNBC treatment.

Gold nanomaterials (Au NMs) have been widely used in cosmetic products for improving the brightening, and reducing the wrinkling of, skin, etc.; however, the dermal safety of Au NMs is rarely concerned. A previous study found that cosmetics could enhance the toxicity of Au nanosheets, but different physicochemical properties of Au NMs will induce different interaction modes with ingredients of cosmetics, potentially leading to different toxicity profiles. In the present study, spherical and rodlike Au NMs were first found in commercial cosmetics, and then Au nanospheres (NSs) with different sizes and Au nanorods (NRs) with different aspect ratios were prepared to simulate these Au NMs in cosmetics and further investigate their toxicity before and after embedment in cosmetics. It was found that the primary sizes, morphologies, and optical absorptions of these Au NSs and NRs before and after embedment were similar; however, their hydrodynamic sizes and zeta potentials were noticeably different. Then, these Au NSs and NRs presented weak or no cytotoxicity against HaCaT keratinocytes, while cosmetic cream could alleviate their cytotoxicity. Moreover, the cream could enhance the accumulation of Au NSs and NRs in the skin of hairless mice, but it also alleviated the toxicological responses of Au NSs and NRs in terms of superoxide dismutase (SOD) elevation and malondialdehyde (MDA) reduction. Therefore, the embedment of Au NSs and NRs into cosmetics can alleviate the in vitro and in vivo dermal toxicities of Au NSs and NRs.

Short-chain fatty acids (SCFAs) are the main microbial fermentation products from dietary fibers in the colon, and it has been speculated that they play a key role in keeping healthy in the whole-body. However, differences in SCFAs concentration in the serum and colon samples had attracted little attention. In this study, we have optimized the extract and analysis methods for the determination of ten SCFAs in both serum and colon content samples. Methanol and acetonitrile were chosen for extraction of SCFAs from serum and colon content samples, respectively. Biological samples were collected from Alzheimer’s disease rats treated by extract of Schisandra chinensis (Turcz.) Baill (SC-extract) were taken as research objects. The results showed that, the relative peak intensities of SCFAs in the colon content from all groups were quite similar, and the trend was identical in the serum samples. Compared with the values in humans, the ratio of ten SCFAs in rat’s colon was similar, while the percent of acetate in rat’s serum was significantly higher. For therapy of Alzheimer’s disease (AD), SC-extract decreased the concentration of butyrate, 3-Methyvalerate, and caproate in the serum samples towards the trend of normal rats. This study may help our understanding of how SCFAs are transported across colonic epithelium in healthy and diseased organisms.

Compound Phyllanthus urinaria (CP), a traditional Chinese herbal remedy, possesses strong anti-cancer effects and is extensively employed in the clinical management of hepatocellular carcinoma (HCC). While lenvatinib and other oral tyrosine kinase inhibitors have been authorized as initial treatments for advanced unresectable HCC, the survival of patients is ultimately restricted due to the gradual development of drug resistance. Fortunately, the co-administration of CP and lenvatinib holds promise for anti-cancer applications. Our objective was to understand the molecular-level mechanisms of bioactive phytocompounds in CP, in order to explore the anti-HCC effects of combining CP and lenvatinib treatment and reveal the underlying mechanisms. Furthermore, we discovered new miRNAs associated with autophagy that are common to both HepG2-derived exosomes and HepG2 cells. These miRNAs play a role in the advancement of HCC and were identified through the utilization of CP and lenvatinib. To assess the anti-HCC effects of CP in combination with lenvatinib, both an in vitro CCK-8 assay and an in vivo xenograft model assay were performed. TEM, NTA, and nano-flow cytometry were employed for the identification of isolated exosomes. To ascertain the miRNA expression patterns in HepG2 cells and HepG2-derived exosomes, miRNA-sequencing analysis was conducted. Further investigation involved the use of real-time PCR, examination of the fusion protein GFP-mRFP-LC3, TEM analysis, and western blotting. In vitro and in vivo, the combination of CP and lenvatinib showed a stronger and more powerful impact on HCC compared to either CP or lenvatinib alone. The combination of CP and lenvatinib had a significant impact on autophagy-related miRNAs in HepG2-derived exosomes and HepG2 cells, as demonstrated by cellular and exosomal miRNA sequencing. Additional tests indicated that the increased inhibition of autophagy in HepG2 cells subjected to CP treatment, as well as the combination of CP and lenvatinib, was accomplished through the regulation of Beclin-1, LC3-II, and P62 expression. In conclusion, our results indicate that the combination of CP and lenvatinib can effectively inhibit HCC by promoting the exosome-mediated suppression of autophagy. This novel therapeutic option is highly efficient and durable, making it a promising treatment for HCC. Moreover, the miRNAs that are differentially expressed and associated with exosome-mediated autophagy, which have been discovered in this study, could potentially be targeted for clinical treatment of HCC.

The kidney, an essential excretory organ of the body, performs a series of crucial physiological functions such as waste removal, maintenance of electrolyte and acid–base balance, and endocrine regulation. Due to its rich blood flow and high metabolic activity, the kidney is susceptible to damage. Currently, kidney injury is classified into acute kidney injury (AKI) and chronic kidney disease (CKD), both of which are associated with high rates of morbidity and mortality on a global scale. The current clinical diagnosis of renal injury relies on the assessment of renal filtration function using creatinine and urea nitrogen as “gold-standard” markers. However, the delayed response time, limited specificity, and reduced accuracy of creatinine and urea nitrogen in evaluating kidney injury have significantly hindered advancements in diagnostic methods for kidney injury. Urinary protein is widely utilized as a biomarker for the early diagnosis of kidney injury due to the selectivity of the glomerular filtration system determining whether proteins can pass through the filtration barrier based on their size and charge. Therefore, as a complex biological sample with varying charges and particle sizes, urinary protein is considered an ideal indicator for monitoring the progression of kidney disease. Exploring the relationship between urinary protein and the advancement of kidney injury based on differences in particle size and charge offers a new perspective for assessing and treating such injuries. Hence, we conducted a comprehensive review of 74 relevant studies to gain a thorough understanding of the physiological mechanism and significance of proteinuria production. The aim was to explore the challenges and opportunities in clinical urine protein detection, as well as to discuss strategies targeting glomerular filtration barriers in order to effectively reduce urine protein levels and treat kidney injury, which could provide a new perspective for identifying the progression of kidney injury.

With the escalating demand for Astragalus polysaccharides products developed from Radix Astragali (RA), the necessity for quality control of polysaccharides in RA has become increasingly urgent. In this study, a specific method for the simultaneous determination of seven monosaccharides in polysaccharides extracted from Radix Astragali (RA) has been developed and validated using ultra-performance liquid chromatography equipped with an ultraviolet detector (UHPLC-UV) for the first time. The 1-phenyl-3-methyl-5-pyrazolone (PMP) derivatizations were separated on a C18 column (Waters ACQUITY^TM, Milfor, MA, USA, 1.8 µm, 2.1 × 100 mm) using gradient elution with a binary system of 5 mm ammonium formate (0.1% formic acid)-acetonitrile for 24 min. Additionally, seven monosaccharides showed good linear relationships (R², 0.9971–0.9995), adequate precision (RSD < 4.21%), and high recoveries (RSD < 4.70%). The established method was used to analyze 109 batches of RA. Results showed that the Astragalus polysaccharides (APSs) mainly consist of mannose (Man), rhamnose (Rha), glucose (Glu), galactose (Gal), arabinose (Ara), xylose (Xyl); and fucose (Fuc); however, their composition was different among RA samples from different growth patterns, species, growth years, and origins, and the growth mode of RA and the age of wild-simulated RA can be accurately distinguished by principal component analysis (PCA). In addition, the immunological activity of APSs were also evaluated jointly by measurement of the NO release with RAW264.7, with the results showing that APSs have a promoting effect on the release of NO and exhibit a significant correlation with Man, Glu, Xyl, and Fuc contents. Accordingly, the new established monosaccharides analytical method and APS-immune activity determination in this study can provide a reference for quality evaluation and the establishment of quality standards for RA.