Factors affecting suboptimal maturation of autogenous arteriovenous fistula in elderly patients with diabetes:A narrative review.

Autogenous arteriovenous fistula (AVF) is considered the preferred vascular access choice for individuals undergoing maintenance hemodialysis (MHD) and is widely utilized in China, as reported by the Dialysis Outcomes and Practice Patterns Study. Despite its popularity, the significant incidence of poor AVF maturation often leads to the need for central venous catheter insertion, increasing the risk of complications like superior vena cava stenosis and catheter-related infections, which in turn raises the overall mortality risk. With the prevalence of diabetes rising globally among the elderly and diabetic kidney disease being a leading cause of end-stage renal disease necessitating renal replacement therapy, our retrospective review aims to explore the various factors affecting AVF maturation in this specific patient population. While there have been numerous studies examining AVF complications in MHD patients, including issues like failure, patency loss, stenosis, thrombosis, poor maturation, and other influencing factors, there remains a gap in large-scale clinical studies focusing on the incidence and risk factors for immature AVF specifically in elderly diabetic patients. This paper delves into the pathophysiological mechanisms, diagnostic criteria, and unique considerations surrounding AVF maturation in elderly diabetic patients, distinguishing them from the general population. Our literature review reveals that elderly diabetic patients exhibit a higher risk of AVF immaturity compared to the general population. Additionally, there exists a continuing discourse regarding several aspects related to this group, including the choice of dialysis access, timing of AVF surgery, and surgical site selection. Furthermore, we delve into the management strategies for vascular access within this specific group with the goal of providing evidence-based guidance for the establishment and maintenance of functional vascular access in elderly diabetic patients.

Sphingosine-1 phosphate receptor 1 (S1PR1) expression maintains stemness of acute myeloid leukemia stem cells.

Acute myeloid leukemia (AML) arises from leukemia stem cells (LSCs) and is maintained by cells which have acquired features of stemness. We compared transcription profiles of AML cells with/without stem cell features defined as in vitro clonogenicity and serial engraftment in immune-deficient mice xenograft model. We used multi-parameter flow cytometry (MPFC) to separate CD34+ bone marrow-derived leukemia cells into sphingosine-1 phosphate receptor 1 (S1PR1)+ and S1PR1- fractions. Cells in the S1PR1+ fraction demonstrated significantly higher clonogenicity and higher engraftment potential compared with those in the S1PR1- fraction. In contrast, CD34+ bone marrow cells from normal samples showed reduced clonogenicity in the S1PR1+ fraction compared with the S1PR1- fraction. Inhibition of S1PR1 expression in an AML cell line reduced the colony-forming potential of KG1 cells. Transcriptomic analyses and rescue experiments indicated PI3K/AKT pathway and MYBL2 are downstream mediators of S1PR1-associated stemness. These findings implicate S1PR1 as a functional biomarker of LSCs and suggest its potential as a therapeutic target in AML treatment.

Lipid droplets-specific fluorescent probe for wash-free imaging and in vivo diagnosis of non-alcoholic fatty liver disease.

Lipid droplets (LDs) dysfunction is closely associated with a multitude of diseases, including nonalcoholic fatty liver disease (NAFLD). Therefore, it is imperative to develop fluorescent probes that specifically target LDs for the early detection and diagnosis of NAFLD. In this study, a series of lipophilic fluorophores CZ1-CZ4 that feature a D-π-A configuration were designed and synthesized based on the carbazole and tricocyanofuran derivatives. The photophysical data revealed that all four probes exhibited large Stokes shifts (~ 120 nm) in high-polarity solvents (e.g., DMSO) and demonstrated enhanced fluorescence in solvents ranging from low-polarity (e.g., 1,4-Dioxane) to high-polarity. Notably, by utilizing probe CZ1, we could specifically visualize LDs and captured high-quality images, even eliminating the need for a time-consuming wash procedure. Moreover, CZ1 enabled monitoring of LDs dynamic changes in-real time within live cells, and importantly, it could be used to effectively distinguish normal and NAFLD tissues at both the organ and in vivo level. This exceptional property of probe CZ1 provides a practical tool for the diagnosis and intervention of NAFLD.

A simple predictor for donor-specific anti-HLA antibody desensitisation in haploidentical haematopoietic stem cell transplantation.

Donor-specific HLA antibody (DSA) has been recognised as an independent risk factor for graft failure in patients undergoing haploidentical haematopoietic stem cell transplantation (HID HSCT). Therapeutic plasma exchange (TPE), as a first-line strategy for DSA desensitisation, can promptly reduce serum DSA levels. This study aimed to investigate DSA characteristics and identify a biomarker predicting the efficacy of DSA desensitisation in patients proceeding to HID HSCT. We retrospectively enrolled 32 patients with DSA from April 2021 to January 2024, and analysed the mean fluorescence intensity (MFI) value of DSA at the different time points of desensitisation treatment. Compared with baseline DSA level before TPE, the median MFI of HLA class I DSA was reduced from 8178.6 to 795.3 (p < 0.001), and HLA class II DSA decreased from 6210.9 to 808.8 (p < 0.001) after TPE. The DSA level in 1:16 diluted pre-TPE serum correlated well with DSA value in post-TPE serum (class I, r = 0.85, p < 0.0001; class II, r = 0.94, p < 0.0001), predicting TPE efficacy in 84.4% of patients. Based on the degree of DSA reduction after TPE, patients were divided into complete responders (decreased by >70%), partial responders (decreased by 30 to 70%) and non-responders (decreased by <30%) and the percentages were 43.8%, 25% and 31.2%, respectively. Non-responders receiving aggressive immunotherapy had longer overall survival compared to those receiving standard strategies (p < 0.05). The 1:16 diluted pre-TPE serum may predict the efficacy of TPE and allow for more rational immunotherapy strategy for patients with DSA proceeding to HID HSCT.

Oleandrin enhances radiotherapy sensitivity in lung cancer by inhibiting the ATM/ATR-mediated DNA damage response.

Despite active clinical trials on the use of Oleandrin alone or in combination with other drugs for the treatment of solid tumors, the potential synergistic effect of Oleandrin with radiotherapy remains unknown. This study reveals a new mechanism by which Oleandrin targets ATM and ATR kinase-mediated radiosensitization in lung cancer. Various assays, including clonogenic, Comet, immunofluorescence staining, apoptosis and Cell cycle assays, were conducted to evaluate the impact of oleandrin on radiation-induced double-strand break repair and cell cycle distribution. Western blot analysis was utilized to investigate alterations in signal transduction pathways related to double-strand break repair. The efficacy and toxicity of the combined therapy were assessed in a preclinical xenotransplantation model. Functionally, Oleandrin weakens the DNA damage repair ability and enhances the radiation sensitivity of lung cells. Mechanistically, Oleandrin inhibits ATM and ATR kinase activities, blocking the transmission of ATM-CHK2 and ATR-CHK1 cell cycle checkpoint signaling axes. This accelerates the passage of tumor cells through the G2 phase after radiotherapy, substantially facilitating the rapid entry of large numbers of inadequately repaired cells into mitosis and ultimately triggering mitotic catastrophe. The combined treatment of Oleandrin and radiotherapy demonstrated superior inhibition of tumor proliferation compared to either treatment alone. Our findings highlight Oleandrin as a novel and effective inhibitor of ATM and ATR kinase, offering new possibilities for the development of clinical radiosensitizing adjuvants.

Pan­cancer analysis on the role of KMT2C expression in tumor progression and immunotherapy.

Histone lysine N-methyltransferase 2C (KMT2C) is involved in transcriptional regulation and DNA damage repair. Mutations in KMT2C have been implicated in the progression, metastasis, and drug resistance of multiple cancer types. However, the roles of KMT2C in the regulation of tumor prognosis, immune cell infiltration and the immune microenvironment in these multiple cancer types remain unclear. Therefore, in the present study, data from The Cancer Genome Atlas and Genotype-Tissue Expression databases were used for KMT2C expression analyses. Kaplan-Meier and univariate Cox regression analyses were also performed to investigate the prognostic role of KMT2C. In addition, Gene Set Enrichment Analysis (GSEA) was conducted to study the KMT2C-related signaling pathways. Tumor immune estimation resource 2 and single-sample GSEA were conducted to investigate the correlation between KMT2C expression and immune cell infiltrations, and Spearman's analysis was conducted to study the correlations among KMT2C, tumor mutational burden, microsatellite instability, immune regulators, chemokines and immune receptors. Immunohistochemistry of patient kidney tumor samples was performed to verify the correlation between KMT2C and programmed death-ligand 1 (PD-L1) expression. Finally, RNA interference, wound healing and colony formation assays were conducted to evaluate the effects of KMT2C expression on cell proliferation and metastasis. The results of the present study demonstrated that KMT2C was highly expressed in multiple cancer types, was a protective factor in kidney renal clear cell carcinoma and ovarian serous cystadenocarcinoma, and a risk factor for lung squamous cell carcinoma and uveal melanoma. In addition, KMT2C levels were negatively correlated with immune-activated pathways and the infiltration of immune cells, and positively correlated with inhibitory immune factors and tumor angiogenesis. Patients with low KMT2C expression had higher objective response rates to immunotherapy, and drug sensitivity analysis indicated that topoisomerase, histone deacetylase, DOT1-like histone H3K79 methyltransferase and G9A nuclear histone lysine methyltransferase inhibitors could potentially be used to treat tumors with high KMT2C expression levels. Finally, the KMT2C and PD-L1 expression levels were shown to be positively correlated, and KMT2C knockdown markedly promoted the proliferation and invasion capacities of A549 cells. In conclusion, the present study revealed that low KMT2C expression may be a promising biomarker for predicting the response of patients with cancer to immunotherapy. Conversely, high KMT2C expression was shown to promote tumor angiogenesis, which may contribute to the formation of the immunosuppressive tumor microenvironment.

Application of acid-activated near-infrared viscosity fluorescent probe targeting lysosomes in cancer visualization.

The higher viscosity and lower pH in lysosomes of cancer cells highlight their potential as biomarkers for cancer. Therefore, the development of acid-activated viscosity fluorescent probes is significant for the early diagnosis and treatment of cancer. Based on this, we have designed and synthesized a near-infrared fluorescent probe based on the 2-(2-hydroxyphenyl)benzothiazole (HBT) group, namely HBTH, to monitor the viscosity changes within lysosomes. It has been demonstrated that HBTH was extremely sensitive to viscosity, with a strong linear relationship between fluorescence intensity and log(viscosity) within the range of (logη) = 0-3.06 (a correlation coefficient of 0.98), proving its capability for quantitative viscosity measurement. In particular, the most obvious fluorescence enhancement of HBTH was only efficiently triggered by the combined effect of low pH and high viscosity. Furthermore, HBTH can rapidly localize to lysosomes by wash-free procedure at a low concentration (100 nM) and achieve high-fidelity imaging within 20 s. It can also monitor the dynamic processes of lysosomes in cells, viscosity changes under drug stimuli, and lysosomal behavior during mitophagy. Importantly, HBTH is capable of identifying tumors in tumor-bearing nude mice through in vivo imaging. These features make HBTH a powerful tool for the early diagnosis and treatment of cancer.

Cinobufacini enhances the therapeutic response of 5-Fluorouracil against gastric cancer by targeting cancer stem cells via AKT/GSK-3ß/ß-catenin signaling axis.

BACKGROUND: Gastric cancer stem cells (GCSCs) play crucial role in the development, recurrence, and resistance of gastric cancer (GC). Cinobufacini, a traditional Chinese medicine, offers significant advantages in improving tumor therapy. However, pre-clinical investigation into the antitumor effect and mechanism of Cinobufacini on GC is still lacking. Additionally, it has not been reported whether Cinobufacini is related to cancer stem cells (CSCs). METHODS: The CCK-8, clone formation, EdU staining, transwell and wound healing experiments were performed to assess the cell toxicity of Cinobufacini and demonstrate the preventive effects of Cinobufacini on proliferation, invasion, and migration of GC cells. Elucidating the underlying mechanism of Cinobufacini in GC based on the transcriptome sequencing. Flow cytometry assays, sphere formation assays, subcutaneous xenograft model in nude mice, and immunofluorescent staining have been used to investigate whether the anti-GC effect of Cinobufacini is associated with GCSCs and enhancing therapeutic response to 5-Fluorouracil (5-FU). RESULTS: Cinobufacini exerts minimal impact on normal human gastric epithelium cell GES-1, while significantly suppressing the proliferation, invasion, and migration of GC cell lines. Additionally, Cinobufacini attenuates the stemness of GCSCs by disrupting the AKT/GSK-3ß/ß-catenin signaling cascade. Moreover, Cinobufacin enhances the anti-tumor effects of 5-FU against GCSCs by reducing in vitro sphere formation and inhibiting subcutaneous graft tumor growth in vivo. CONCLUSIONS: Cinobufacini enhances the therapeutic response of 5-FU against GC by targeting CSCs via AKT/GSK-3ß/ß-catenin signaling axis. Our findings offer a crucial insight into the molecular mechanism of Cinobufacini's anticancer activity in GC.

Multifunctional lipid droplet probes for observing the polarity change of ferroptosis, inflammation, fatty liver and evaluating the efficacy of drugs.

BACKGROUND: Lipid droplets (LDs) polarity is intricately linked to diverse biological processes and diseases. The visualization of LDs-polarity is of vital importance but challenging due to the lack of high-specificity, high-sensitivity and large-Stokes shift probes for real-time tracking LDs-polarity in biological systems. RESULTS: Four D-π-A based fluorescent probes (TPA-TCF1-TPA-TCF4) have been developed by combining tricyanofuran (an electron acceptor, A) and triphenylamine (an electron donor, D) derivatives with different terminal groups. Among them, TPA-TCF1 and TPA-TCF4 exhibit excellent polar sensitivity, large Stokes shift (≥182 nm in H2O), and efficient LDs targeting ability. In particular, TPA-TCF4 is capable of monitoring the change of LDs-polarity during ferroptosis, inflammation, apoptosis of cancer cell, and fatty liver. SIGNIFICANCE: All these features render TPA-TCF4 a versatile tool for pharmacodynamic evaluation of anti-cancer drugs, in-depth understanding of the biological effect of LDs on ferroptosis, and medical diagnosis of LDs-polarity related diseases.

Encapsulation of three different types of polyphenols in casein using a customized pH-driven method: Preparation and characterization.

Phenolic compounds represent natural compounds endowed with diverse biological functionalities. However, their inherent limitations, characterized by poor water solubility and low oral bioavailability, limit their broader applications. Encapsulation delivery systems are emerging as a remedy, able to ameliorate these limitations by enhancing the stability and solubility of phenolic compounds. In this study, a novel, customized pH-driven approach was developed by determining the optimal deprotonation and protonation points of three different types of polyphenols: ferulic acid, resveratrol, and rhein. The polyphenols were successfully encapsulated in a casein carrier. The solubility, stability, LogD, and LogS curves of the three polyphenols at different pH values were analyzed to identify the optimal deprotonation points for ferulic acid (pH 9), resveratrol (pH 11), and rhein (pH 10). Based on these findings, three different nanoparticles were prepared. The encapsulation efficiencies of the three phenolic compounds were 95.86%, 94.62%, and 94.18%, respectively, and the casein nanoparticles remained stable at room temperature for seven days. FTIR spectroscopy, fluorescence spectroscopy, and molecular docking study substantiated the encapsulation of phenolic compounds within the hydrophobic core of casein-based complexes, facilitated by hydrogen bonding interactions and hydrophobic interactions. Furthermore, the analysis of antioxidant activity elucidated that casein nanoparticles heightened both the water solubility and antioxidant efficacy of the phenolic compounds. This customized encapsulation technique, by establishing a transitional pH value, resolves the challenges of chemical instability and facile degradation of polyphenols under alkaline conditions in the application process of pH-driven methods. It presents novel insights for the application of polyphenols in the domains of food and biomedical fields.

Evaluation of transport mechanisms of methotrexate in human choriocarcinoma cell lines by LC-MS/MS.

Methotrexate (MTX) is commonly prescribed as the initial treatment for gestational trophoblastic neoplasia (GTN), but MTX monotherapy may not be effective for high-risk GTN and choriocarcinoma. The cellular uptake of MTX is essential for its pharmacological activity. Thus, our study aimed to investigate the cellular pharmacokinetics and transport mechanisms of MTX in choriocarcinoma cells. For the quantification of MTX concentrations in cellular matrix, a liquid chromatography-tandem mass spectrometry method was created and confirmed initially. MTX accumulation in BeWo, JEG-3, and JAR cells was minimal. Additionally, the mRNA levels of folate receptor α (FRα) and breast cancer resistance protein (BCRP) were relatively high in the three choriocarcinoma cell lines, whereas proton-coupled folate transporter (PCFT), reduced folate carrier (RFC), and organic anion transporter (OAT) 4 were low. Furthermore, the expression of other transporters was either very low or undetectable. Notably, the application of inhibitors and small interfering RNAs (siRNAs) targeting FRα, RFC, and PCFT led to a notable decrease in the accumulation of MTX in BeWo cells. Conversely, the co-administration of multidrug resistance protein 1 (MDR1) and BCRP inhibitors increased MTX accumulation. In addition, inhibitors of OATs and organic-anion transporting polypeptides (OATPs) reduced MTX accumulation, while peptide transporter inhibitors had no effect. Results from siRNA knockdown experiments and transporter overexpression cell models indicated that MTX was not a substrate of nucleoside transporters. In conclusion, the results indicate that FRα and multiple transporters such as PCFT, RFC, OAT4, and OATPs are likely involved in the uptake of MTX, whereas MDR1 and BCRP are implicated in the efflux of MTX from choriocarcinoma cells. These results have implications for predicting transporter-mediated drug interactions and offer potential directions for further research on enhancing MTX sensitivity.

Sanggenol L induces ferroptosis in non-small cell lung cancer cells via regulating the miR-26a-1-3p/MDM2/p53 signaling pathway.

Ferroptosis is a regulated cell death marked by iron-dependent lipid peroxidation. Tumor cells that survive by evading chemotherapy-induced apoptosis are vulnerable to ferroptosis. Therefore, it is particularly urgent to explore active ingredients that can selectively induce ferroptosis in cancer cells. Here, we revealed that sanggenol L, the active agent of Morus Bark, predisposed non-small cell lung cancer (NSCLC) cells to ferroptosis, evidenced by reactive oxygen species (ROS) accumulation, glutathione depletion, mitochondrial shrinkage, and lipid peroxidation. Furthermore, the ferroptosis-related miRNA array showed that sanggenol L treatment upregulated the level of miR-26a-1-3p, which directly targeted the E3 ubiquitin ligase MDM2. In addition, silencing MDM2 by miR-26a-1-3p resulted in a notable increase in p53 protein levels and decrease of its downstream target SLC7A11, ultimately triggered ferroptosis. The subcutaneous xenograft model and patient-derived tumor xenograft (PDX) model of NSCLC further confirmed the anti-tumor efficacy and safety of sanggenol L in vivo. Collectively, our data suggest that miR-26a-1-3p/MDM2/p53/SLC7A11 signaling axis plays a key role in sanggenol L-induced ferroptosis, which implies that sanggenol L can serves as an anticancer therapeutic arsenal for NSCLC.

Hypoxia makes EZH2 inhibitor not easy-advances of crosstalk between HIF and EZH2.

Histone methylation plays a crucial role in tumorigenesis. Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that regulates chromatin structure and gene expression. EZH2 inhibitors (EZH2is) have been shown to be effective in treating hematologic malignancies, while their effectiveness in solid tumors remains limited. One of the major challenges in the treatment of solid tumors is their hypoxic tumor microenvironment. Hypoxia-inducible factor 1-alpha (HIF-1α) is a key hypoxia responder that interacts with EZH2 to promote tumor progression. Here we discuss the implications of the relationship between EZH2 and hypoxia for expanding the application of EZH2is in solid tumors.

Genome-wide analysis of bZIP transcription factors and their expression patterns in response to methyl jasmonate and low-temperature stresses in Platycodon grandiflorus.

Background: Platycodon grandiflorus belongs to the genus Platycodon and has many pharmacological effects, such as expectorant, antitussive, and anti-tumor properties. Among transcription factor families peculiar to eukaryotes, the basic leucine zipper (bZIP) family is one of the most important, which exists widely in plants and participates in many biological processes, such as plant growth, development, and stress responses. However, genomic analysis of the bZIP gene family and related stress response genes has not yet been reported in P. grandiflorus. Methods: P. grandiflorus bZIP (PgbZIP) genes were first identified here, and the phylogenetic relationships and conserved motifs in the PgbZIPs were also performed. Meanwhile, gene structures, conserved domains, and the possible protein subcellular localizations of these PgbZIPs were characterized. Most importantly, the cis-regulatory elements and expression patterns of selected genes exposed to two different stresses were analyzed to provide further information on PgbZIPs potential biological roles in P. grandiflorus upon exposure to environmental stresses. Conclusions: Forty-six PgbZIPs were identified in P. grandiflorus and divided into nine groups, as displayed in the phylogenetic tree. The results of the chromosomal location and the collinearity analysis showed that forty-six PgbZIP genes were distributed on eight chromosomes, with one tandem duplication event and eleven segmental duplication events identified. Most PgbZIPs in the same phylogenetic group have similar conserved motifs, domains, and gene structures. There are cis-regulatory elements related to the methyl jasmonate (MeJA) response, low-temperature response, abscisic acid response, auxin response, and gibberellin response. Ten PgbZIP genes were selected to study their expression patterns upon exposure to low-temperature and MeJA treatments, and all ten genes responded to these stresses. The real-time quantitative polymerase chain reaction (RT-qPCR) results suggest that the expression levels of most PgbZIPs decreased significantly within 6 h and then gradually increased to normal or above normal levels over the 90 h following MeJA treatment. The expression levels of all PgbZIPs were significantly reduced after 3 h of the low-temperature treatment. These results reveal the characteristics of the PgbZIP family genes and provide valuable information for improving P. grandiflorus's ability to cope with environmental stresses during growth and development.

Synthesis and anti-tumor activities of three newly designed organotin(IV) carboxylates complexes.

Three distinctive end group-containing organotin (IV) carboxylates complexes (YDCOOSn, CLCOOSn and BZCOOSn) were designed and synthesized. Together with theoretical calculations, a thorough examination was carried out to investigate the photophysical properties of these compounds. The cytotoxicity of the synthesized compounds was tested using normal cell line GES-1 and was assessed against four cancer cell lines (A549, Hela, H1299 and HepG2). The outcomes of the experiments demonstrated that these complexes had superior selectivity than cisplatin towards cancerous cells, particularly in the A549 cell line. BZCOOSn was selected as a candidate compound for additional research because it exhibited the lowest IC50 value and the most impressive inducing effect on cell death and G2/M phase arrest. Increased caspase-3 and -9 enzyme activity, a decline in mitochondrial membrane potential (MMP), characteristic nuclear apoptotic morphology, and an accumulation of intracellular reactive oxygen species (ROS) were seen in A549 exposed to BZCOOSn. These findings demonstrated that BZCOOSn exhibited strong cytotoxicity by triggering cell death in A549 via the mitochondrial route. Furthermore, using the scratch wound healing assay, it was discovered that BZCOOSn reduced the migration of A549 cancerous cells. These data all pointed to BZCOOSn as a possible candidate for more research and development as a chemotherapeutic drug.

Triterpenoids from the leaves of Eleutherococcus sessiliflorus, and their antiproliferative activities in TNF-α induced HFLS-RA cells.

Five undescribed elesesterpenes L-U, along with nine known 3,4-seco-lupane-type triterpenoids were isolated from the leaves of Eleutherococcus sessiliflorus (Rupr. & Maxim.) S. Y. Hu. Elesesterpene L-S, and U were lupane-type triterpenoids, whereas elesesterpene T was an oleanane-type triterpenoid, probably artifact, as suggested by LC-MS analysis. Out of the nine known compounds, five were initially identified in E. sessiliflorus. Moreover, their structures were definitively determined using spectroscopic analyses, and the absolute configurations of elesesterpenes L-M and sachunogenin 3-O-glucoside were clarified using X-ray crystallographic techniques. The absolute configuration of elesesterpene T was determined by measuring and calculating its ECD. In addition, all compounds were tested to examine their ability to inhibit the proliferation of HFLS-RA cells induced by TNF-α in vitro. Elesesterpene M, chiisanogenin, chiisanoside, and 3-methylisochiisanoside significantly inhibited HFLS-RA proliferation.

Natural products reverse cancer multidrug resistance.

Cancer stands as a prominent global cause of death. One of the key reasons why clinical tumor chemotherapy fails is multidrug resistance (MDR). In recent decades, accumulated studies have shown how Natural Product-Derived Compounds can reverse tumor MDR. Discovering novel potential modulators to reduce tumor MDR by Natural Product-Derived Compounds has become a popular research area across the globe. Numerous studies mainly focus on natural products including flavonoids, alkaloids, terpenoids, polyphenols and coumarins for their MDR modulatory activity. Natural products reverse MDR by regulating signaling pathways or the relevant expressed protein or gene. Here we perform a deep review of the previous achievements, recent advances in the development of natural products as a treatment for MDR. This review aims to provide some insights for the study of multidrug resistance of natural products.

MSX1+PDGFRAlow limb mesenchyme-like cells as an efficient stem cell source for human cartilage regeneration.

Degenerative bone disorders have a significant impact on global health, and regeneration of articular cartilage remains a challenge. Existing cell therapies using mesenchymal stromal cells (MSCs) have shown limited efficacy, highlighting the necessity for alternative stem cell sources. Here, we have identified and characterized MSX1+ mesenchymal progenitor cells in the developing limb bud with remarkable osteochondral-regenerative and microenvironment-adaptive capabilities. Single-cell sequencing further revealed the presence of two major cell compositions within the MSX1+ cells, where a distinct PDGFRAlow subset retained the strongest osteochondral competency and could efficiently regenerate articular cartilage in vivo. Furthermore, a strategy was developed to generate MSX1+PDGFRAlow limb mesenchyme-like (LML) cells from human pluripotent stem cells that closely resembled their mouse counterparts, which were bipotential in vitro and could directly regenerate damaged cartilage in a mouse injury model. Together, our results indicated that MSX1+PDGFRAlow LML cells might be a prominent stem cell source for human cartilage regeneration.

Factors influencing family resilience in adult patients with acute leukemia undergoing chemotherapy: A qualitative study.

Objective: To explore the factors influencing family resilience in adult patients with acute leukemia undergoing chemotherapy, with the aim of providing a theoretical basis for the development of strategies to strengthen their family resilience. Methods: A descriptive phenomenological qualitative research method was used to select 11 adult acute leukemia chemotherapy patients for semi-structured interviews. Colaizzi 7-step analysis and NVivo 12.0 were used to summarize information and refine themes. Results: The main outcomes consisted of two themes and 11 sub-themes: protective factors for family resilience (positive traits, cognitive restructuring, positive family beliefs, organizational flexibility, clear communication, and social support) and risk factors for family resilience (symptom burden, self-concealment, role overload, economic distress, and social alienation). Conclusions: Health care professionals should pay attention to screening protective and risk factors for family resilience in adult acute leukemia chemotherapy patients, affirming the positive role of internal and external resources available in the family in stressful situations, alleviating patients' negative experiences, and promoting the recovery of family function.

Platelet rich plasma alleviates endometritis induced by lipopolysaccharide in mice via inhibiting TLR4/NF-κB signaling pathway.

BACKGROUND: Endometritis is an inflammatory reaction of the lining of uterus, leading to the occurrence of infertility. Platelet rich plasma (PRP) has been proven to exhibit extremely effective for the treatment of endometrium-associated infertility, but the mechanism of its prevention for endometritis remains unclear. OBJECTIVE: The present study aimed to investigate the protective effect of PRP against endometritis induced by lipopolysaccharide (LPS) and elucidate the mechanism underlying these effects. METHODS: Mouse model of endometritis was established by intrauterine perfusion of LPS. PRP intrauterine infusion was administered at 24 h after LPS induction. After another 24 h, the uterine tissues were harvested to observe histopathological changes, production of proinflammatory cytokines, variation of the Toll-like receptor 4/nuclear factor κB (TLR4/NF-κB) signaling pathways, and validated the anti-inflammatory effect of PRP. The myeloperoxidase (MPO) activity and concentration of nitric oxide (NO) were determined using assay kit. Proinflammatory chemokines (tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6)) were measured by ELISA and Real-Time PCR. The activity of TLR4/NF-κB pathway in uterine tissues was measured by Western blotting. RESULTS: Hematoxylin-eosin staining (H&E) appeared that PRP remarkably relieved the impairment of uterine tissues. Detection of MPO activity and concentration of NO revealed that PRP treatment distinctly mitigated infiltration of inflammatory cells in mice with endometritis induced by LPS. PRP treatment significantly affected the expression of TNF-α, IL-1ß, and IL-6. PRP was also found to suppress LPS-induced activation of TLR4/NF-κB pathway. CONCLUSION: PRP effectively alleviates LPS-induced endometritis via restraining the signal pathway of TLR4/NF-κB. These findings provide a solid foundation for PRP as a potential therapeutic agent for endometritis.