Multifunctional Nanocarrier for Synergistic Treatment of Alzheimer's Disease by Inhibiting ß-Amyloid Aggregation and Scavenging Reactive Oxygen Species.

The excessive depositions of ß-amyloid (Aß) and abnormal level of reactive oxygen species (ROS) are considered as the important pathogenic factors of Alzheimer's disease (AD). Strategies targeting only one of them have no obvious effects in clinic. In this study, a multifunctional nanocarrier CICe@M-K that crosses the blood-brain barrier (BBB) efficiently was developed for inhibiting Aß aggregation and scavenging ROS synchronously. Antioxidant curcumin (Cur) and photosensitizer IR780 were loaded in mesoporous silica nanomaterials (MSNs). Their surfaces were grafted with cerium oxide nanoparticles (CeO2 NPs) and a short peptide K (CKLVFFAED). Living imaging showed that CICe@M-K was mainly distributed in the brain, liver, and kidneys, indicating CICe@M-K crossed BBB efficiently and accumulated in brain. After the irradiation of 808 nm laser, Cur was continuously released. Both of Cur and the peptide K can recognize and bind to Aß through multiple interaction including π-π stacking interaction, hydrophobic interaction, and hydrogen bond, inhibiting Aß aggregation. On the other hand, Cur and CeO2 NPs cooperate to relieve the oxidative stress in the brains by scavenging ROS. In vivo assays showed that the CICe@M-K could diminish Aß depositions, alleviate oxidative stress, and improve cognitive ability of the APP/PS1 AD mouse model, which demonstrated that CICe@M-K is a potential agent for AD treatment.

Air pollution and skin diseases: A comprehensive evaluation of the associated mechanism.

Air pollutants deteriorate the survival environment and endanger human health around the world. A large number of studies have confirmed that air pollution jeopardizes multiple organs, such as the cardiovascular, respiratory, and central nervous systems. Skin is the largest organ and the first barrier that protects us from the outside world. Air pollutants such as particulate matter (PM), polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs) will affect the structure and function of the skin and bring about the development of inflammatory skin diseases (atopic dermatitis (AD), psoriasis), skin accessory diseases (acne, alopecia), auto-immune skin diseases (cutaneous lupus erythematosus(CLE) scleroderma), and even skin tumors (melanoma, basal cell carcinoma (BCC), squamous-cell carcinoma (SCC)). Oxidative stress, skin barrier damage, microbiome dysbiosis, and skin inflammation are the pathogenesis of air pollution stimulation. In this review, we summarize the current evidence on the effects of air pollution on skin diseases and possible mechanisms to provide strategies for future research.

A piezoelectric-driven microneedle platform for skin disease therapy.

With over a million cases detected each year, skin disease is a global public health problem that diminishes the quality of life due to its difficulty to eradicate, propensity for recurrence, and potential for post-treatment scarring. Photodynamic therapy (PDT) is a treatment with minimal invasiveness or scarring and few side effects, making it well tolerated by patients. However, this treatment requires further research and development to improve its effective clinical use. Here, a piezoelectric-driven microneedle (PDMN) platform that achieves high efficiency, safety, and non-invasiveness for enhanced PDT is proposed. This platform induces deep tissue cavitation, increasing the level of protoporphyrin IX and significantly enhancing drug penetration. A clinical trial involving 25 patients with skin disease was conducted to investigate the timeliness and efficacy of PDMN-assisted PDT (PDMN-PDT). Our findings suggested that PDMN-PDT boosted treatment effectiveness and reduced the required incubation time and drug concentration by 25% and 50%, respectively, without any anesthesia compared to traditional PDT. These findings suggest that PDMN-PDT is a safe and minimally invasive approach for skin disease treatment, which may improve the therapeutic efficacy of topical medications and enable translation for future clinical applications.

Real-world evidence of combined treatment of biologics and exclusive enteral nutrition in patients with ileum-dominant Crohn's disease: A multicenter study.

BACKGROUND & AIMS: Although biologics were prescribed to achieve and maintain clinical remission of active Crohn's disease (CD), almost half of patients experienced a loss of response or intolerance. Here, we investigated the efficacy of combined treatment of biologics and 16-weeks exclusive enteral nutrition (EEN) in moderate-to-severe CD patients with small intestine lesions. METHODS: This was a real-world, multicenter retrospective study, from October 2016 to March 2023, medical records of patients registered at three IBD centers were reviewed for patients with ileal or ileocolonic CD in moderate-to-severe activity. All patients received treatment of biologics with concomitant 16-week EEN (BioEEN) or biologics alone (Bio). The clinical outcomes and endoscopic outcomes were assessed at week 16 and 52. RESULTS: There was no statistically significant difference between Bio (97 patients) and BioEEN group (100 patients) at baseline for demographic and clinical characteristics. Compared to treatment with biologics alone, patients with BioEEN treatment achieved higher rates of clinical response (95.0% vs. 66.0%), clinical remission (87.0% vs. 52.6%), endoscopic response (91.4% vs. 47.4%) including mucosal healing (85.7% vs. 23.7%) at week 16. The superiority of BioEEN sustained in maintenance, with 84.7% (vs. 49.1%) clinical response, 77.8% (vs. 38.6%) clinical remission, 69.2% (vs. 32.6%) endoscopic response and 51.9% (vs. 18.6%) mucosal healing at week 52. CONCLUSIONS: Combined treatment of biologics and 16-week EEN was an efficient therapeutic strategy with affirmative effectiveness for small intestine diseases of active CD.

Efficacy of consolidation of immune checkpoint inhibitor after chemoradiation for unresectable, locally advanced PD­L1 negative non­small cell lung cancer: A systematic review and meta­analysis.

Chemoradiotherapy (CRT) followed by consolidation of immune checkpoint inhibitors (ICIs), such as durvalumab or pembrolizumab, for patients with unresectable, locally advanced non-small cell lung cancer (NSCLC) with tumor PD-L1 expression <1% remains a topic of controversy. Previous studies from PubMed, Cochrane Library and Embase databases were searched for a meta-analysis. A total of 16 studies were included in part one of the meta-analysis and it was observed that consolidation of ICIs after CRT improved overall survival (OS) [hazard ratio (HR) 1.46; P=0.005] and progression-free survival (PFS) (HR 1.26; P=0.023) for the patients with PD-L1 expression ≥1% compared with those with PD-L1 expression <1%. Then, 15 studies were included in part two of the meta-analysis and the results indicated that the pooled 1, 2 and 3-year OS were 77% vs. 83% (P=0.07), 55% vs. 59% (P=0.327) and 38% vs. 51% (P=0.006) for CRT alone compared with CRT followed by consolidation of ICIs, respectively. The pooled 1, 2 and 3-year PFS were 51% vs. 53% (P=0.632), 29% vs. 40% (P=0.015) and 20% vs. 28% (P=0.153) for CRT alone compared with CRT followed by consolidation of ICIs, respectively. The findings of the present study highlighted that the benefits of CRT followed by consolidation of ICIs were higher compared with CRT alone in patients with unresectable, locally advanced NSCLC and PD-L1 expression <1%. Consolidation of ICIs after CRT would provide greater benefits for locally advanced NSCLC patients with PD-L1 expression ≥1% compared with those with PD-L1 expression <1%.

Phytochemical Profile and Bioactivity of Bound Polyphenols Released from Rosa roxburghii Fruit Pomace Dietary Fiber by Solid-State Fermentation with Aspergillus niger.

This study aimed to investigate the phytochemical profile, bioactivity, and release mechanism of bound polyphenols (BPs) released from Rosa roxburghii fruit pomace insoluble dietary fiber (RPDF) through solid-state fermentation (SSF) with Aspergillus niger. The results indicated that the amount of BPs released from RPDF through SSF was 17.22 mg GAE/g DW, which was significantly higher than that achieved through alkaline hydrolysis extraction (5.33 mg GAE/g DW). The BPs released through SSF exhibited superior antioxidant and α-glucosidase inhibitory activities compared to that released through alkaline hydrolysis. Chemical composition analysis revealed that SSF released several main compounds, including ellagic acid, epigallocatechin, p-hydroxybenzoic acid, quercetin, and 3,4-dihydroxyphenylpropionic acid. Mechanism analysis indicated that the disruption of tight structure, chemical bonds, and hemicellulose was crucial for the release of BPs from RPDF. This study provides valuable information on the potential application of SSF for the efficient release of BPs from RPDF, contributing to the utilization of RPDF as a functional food ingredient.

Habitat-Based Radiomics for Predicting EGFR Mutations in Exon 19 and 21 From Brain Metastasis.

RATIONALE AND OBJECTIVES: To explore and externally validate habitat-based radiomics for preoperative prediction of epidermal growth factor receptor (EGFR) mutations in exon 19 and 21 from MRI imaging of non-small cell lung cancer (NSCLC)-originated brain metastasis (BM). METHODS: A total of 170, 62 and 61 patients from center 1, center 2 and center 3, respectively were included. All patients underwent contrast-enhanced T1-weighted (T1CE) and T2-weighted (T2W) MRI scans. Radiomics features were extracted from the tumor active (TA) and peritumoral edema (PE) regions in each MRI slice. The most important features were selected by the least absolute shrinkage and selection operator regression to develop radiomics signatures based on TA (RS-TA), PE (RS-PE) and their combination (RS-Com). Receiver operating characteristic (ROC) curve analysis was performed to access performance of radiomics models for both internal and external validation cohorts. RESULTS: 10, four and six most predictive features were identified to be strongly associated with the EGFR mutation status, exon 19 and exon 21, respectively. The RSs derived from the PE region outperformed those from the TA region for predicting the EGFR mutation, exon 19 and exon 21. The RS-Coms generated the highest performance in the primary training (AUCs, RS-EGFR-Com vs. RS-exon 19-Com vs. RS-exon 21-Com, 0.955 vs. 0.946 vs. 0.928), internal validation (AUCs, RS-EGFR-Com vs. RS-exon 19-Com vs. RS-exon 21-Com, 0.879 vs. 0.819 vs. 0.882), external validation 1 (AUCs, RS-EGFR-Com vs. RS-exon 19-Com vs. RS-exon 21-Com, 0.830 vs. 0.825 vs. 0.822), and external validation 2 (AUCs, RS-EGFR-Com vs. RS-exon 19-Com vs. RS-exon 21-Com, 0.812 vs. 0.818 vs. 0.800) cohort. CONCLUSION: The developed habitat-based radiomics model can be used to accurately predict the EGFR mutation subtypes, which may potentially guide personalized treatments for NSCLC patients with BM.

Epidemiological Surveillance: Genetic Diversity of Rotavirus Group A in the Pearl River Delta, Guangdong, China in 2019.

Objective: This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A (RVA) in the Pearl River Delta region of Guangdong Province, China. Methods: This study included individuals aged 28 days-85 years. A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens, including RVA, using a Gastrointestinal Pathogen Panel, followed by genotyping, virus isolation, and complete sequencing to assess the genetic diversity of RVA. Results: The overall RVA infection rate was 14.59% (103/706), with an irregular epidemiological pattern. The proportion of co-infection with RVA and other pathogens was 39.81% (41/103). Acute gastroenteritis is highly prevalent in young children aged 0-1 year, and RVA is the key pathogen circulating in patients 6-10 months of age with diarrhea. G9P[8] (58.25%, 60/103) was found to be the predominant genotype in the RVA strains, and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic analysis. Recombination analysis showed that gene reassortment events, selection pressure, codon usage bias, gene polymorphism, and post-translational modifications (PTMs) occurred in the G9P[8] and G3P[8] strains. Conclusion: This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of China, further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic diversity. Strengthening the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development.

[Study on the antimicrobial effect of new bioactive glass against common bacteria in apical periodontitis of deciduous teeth].

PURPOSE: To study the antimicrobial effect of different concentrations of new bioactive glass(BG) on common bacteria in apical periodontitis of deciduous teeth. METHODS: The diameter (mm) of the inhibitory rings formed after treatment of Enterococcus faecalis, Porphyromonas gingivalis and Clostridium nucleatum with the new bioactive glass was detected and observed by paper diffusion method, and the minimal inhibitory concentration(MIC), minimal bactericidal concentration (MBC) and minimal biofilm eradication concentration (MBEC) of E. faecalis, P. gingivalis and C. pseudomallei were determined. The mixed plaques of the three bacteria were treated with 20, 40, 60 and 80 mg/mL of the new bioactive glass for 24 h. The results were analyzed by laser confocal microscopy. The antibacterial effect of the new bioactive glass on the mixed plaque was observed by confocal laser scanning microscopy (CLSM). Statistical analysis was performed with GraphPad Prism 10.0 software. RESULTS: The new bioactive glass showed strong antibacterial potential against the common bacteria of apical periodontitis; the MBEC of the new bioactive glass on the plaque was significantly greater than MIC and MBC of Enterococcus faecalis, Porphyromonas gingivalis and Clostridium nucleatum, and as the concentration of the new bioactive glass increased, the number of dead bacteria in the mixed plaque increased, and there was significant difference from that of the blank control group (P＜0.05). CONCLUSIONS: The novel bioactive glass shows significant antibacterial efficacy against Enterococcus faecalis, Porphyromonas gingivalis and Clostridium nucleatum, which are the common bacteria in apical periodontitis of deciduous teeth.

[The relationship between the expression of PGE2 and COX-2 and the osteogenic activity and oxygen level of alveolar bone].

PURPOSE: To study the relationship between the expression of prostaglandin E2 (PGE2) and cyclooxygenase-2 (COX-2) and the osteogenic activity and oxygen level of alveolar bone. METHODS: The alveolar bones of 56 patients with chronic periodontitis who received dental treatment from March 2021 to March 2023 were collected as the experimental (periodontitis) group, and the healthy alveolar bones of 53 patients who received dental treatment during the same period were selected as the control group. The osteoblasts were cultured by tissue block culture, and modified Kaplow's alkaline phosphatase (ALP) staining was used to identify the cells. COX-2, PGE2 and osteoclastogenesis inhibitory factor (OPG) receptor activator of nuclear factor-κb ligand (RANKL) and other indicators were determined by ELISA. PGE2, COX-2, OPG, internal oxygen level, ALP, RANKL and their correlation were compared between the two groups. Statistical analysis was performed with SPSS 27.0 software package. RESULTS: PGE2, COX-2 and RANKL in periodontitis group were significantly higher than those in the control group, but OPG, internal oxygen level and ALP were significantly lower than those in the control group (P＜0.05). PGE2 and COX2 were highly positively correlated with OPG, internal oxygen level and ALP, but were highly positively correlated with RANKL(P＜0.05). CONCLUSIONS: The expression of PGE2 and COX-2 is highly negatively correlated with ALP and oxygen levels. Clinical treatment may consider increasing oxygen levels, increasing oxygen partial pressure, and regulating ALP levels by drugs, so as to change the inflammatory condition of periodontitis or other dental diseases.

Active Components of Pueraria lobata through the MAPK/ERK Signaling Pathway Alleviate Iron Overload in Alcoholic Liver Disease.

OBJECTIVE: To delve into the primary active ingredients and mechanism of Pueraria lobata for alleviating iron overload in alcoholic liver disease. METHODS: Pueraria lobata's potential targets and signaling pathways in treating alcohol-induced iron overloads were predicted using network pharmacology analysis. Then, animal experiments were used to validate the predictions of network pharmacology. The impact of puerarin or genistein on alcohol-induced iron accumulation, liver injury, oxidative stress, and apoptosis was assessed using morphological examination, biochemical index test, and immunofluorescence. Key proteins implicated in linked pathways were identified using RT-qPCR, western blot analysis, and immunohistochemistry. RESULTS: Network pharmacological predictions combined with animal experiments suggest that the model group compared to the control group, exhibited activation of the MAPK/ERK signaling pathway, suppression of hepcidin expression, and aggravated iron overload, liver damage, oxidative stress, and hepatocyte death. Puerarin and genistein, the active compounds in Pueraria lobata, effectively mitigated the aforementioned alcohol-induced effects. No statistically significant disparities were seen in the effects above between the two groups receiving drug therapy. CONCLUSION: This study preliminarily demonstrated that puerarin and genistein in Pueraria lobata may increase hepcidin production to alleviate alcohol-induced iron overload by inhibiting the MAPK/ERK signaling pathway.

A Real-time augmented reality robot integrated with artificial intelligence for skin tumor surgery - experimental study and case series.

BACKGROUND: Skin tumors affect many people worldwide, and surgery is the first treatment choice. Achieving precise preoperative planning and navigation of intraoperative sampling remains a problem and is excessively reliant on the experience of surgeons, especially for Mohs surgery for malignant tumors. MATERIALS AND METHODS: To achieve precise preoperative planning and navigation of intraoperative sampling, we developed a real-time augmented reality (AR) surgical system integrated with artificial intelligence (AI) to enhance three functions: AI-assisted tumor boundary segmentation, surgical margin design, and navigation in intraoperative tissue sampling. Non-randomized controlled trials were conducted on manikin, tumor-simulated rabbits, and human volunteers in xxx Laboratory to evaluate the surgical system. RESULTS: The results showed that the accuracy of the benign and malignant tumor segmentation were 0.9556 and 0.9548, respectively, and the average AR navigation mapping error was 0.644 mm. The proposed surgical system was applied in 106 skin tumor surgeries, including intraoperative navigation of sampling in 16 Mohs surgery cases. Surgeons who have used this system highly recognize it. CONCLUSIONS: The surgical system highlighted the potential to achieve accurate treatment of skin tumors and to fill the gap in global research on skin tumor surgery systems.

Bioactive solanidane steroidal alkaloids from Solanum lyratum.

Six previously unreported solanidane steroidal alkaloids, namely lyrasolanosides A-F, were isolated from Solanum lyratum. In addition, five known steroidal alkaloids were also identified. The structures of these compounds were determined through the use of NMR, HRESIMS,UV, IR and ECD analysis. To assess their bioactivities, the cytotoxic effects of the six previously unreported compounds were evaluated on A549 cells. The results revealed that lyrasolanoside B (2) exhibited the highest potency among them. Lyrasolanoside B (2) exhibited significant inhibition of cell migration, invasion, and adhesion dramatically. Mechanistically, it was found to suppress the activity of JAK2/STAT3 signaling pathway by downregulating the expression of phosphorylated JAK2/STAT3 in an exosome-dependent manner. In addition, lyrasolanoside B (2) was found to significantly upregulate the expression of E-cadherin and downregulate the expression of N-cadherin and vimentin. These findings indicate that lyrasolanoside B (2) inhibits the metastasis of A549 cells by suppressing exosome-mediated EMT. These findings suggest that lyrasolanoside B (2) may inhibit the metastasis of lung cancer by regulating A549-derived exosomes.

Impact of Metal Salt Oxidants and Preparation Technology on Efficacy of Bacterial Cellulose/Polypyrrole Flexible Conductive Fiber Membranes.

In this study, we investigated the preparation and characterization of flexible conductive fiber membranes (BC/PPy) using different metal salt oxidants on bacterial cellulose (BC) and pyrrole (Py) in the in situ polymerization and co-blended methods, respectively. The effects of these oxidants, namely, ferric chloride hexahydrate (FeCl3·6H2O) and silver nitrate (AgNO3), on the structural characterization, conductivity, resistance value and thermal stability of the resulting materials were assessed by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, Raman spectroscopy and X-ray photoelectron spectroscopy (XPS). A comparative study revealed that the BC/PPy conductive fiber membrane prepared using FeCl3·6H2O as the oxidant had a resistance value of 12 Ω, while the BC/PPy conductive fiber membrane prepared using AgNO3 as the oxidant had an electrical resistance value of 130 Ω. The conductivity of the same molar ratio of BC/PPy prepared using FeCl3·6H2O as an oxidant was 10 times higher than that of the BC/PPy prepared using AgNO3 as an oxidant. Meanwhile, the resistance values of the conductive fiber membranes prepared from BC and PPy by the co-blended method were much higher than the BC/PPy prepared by in situ polymerization. SEM and XPS analyses revealed that when FeCl3·6H2O was used as the oxidant, the Fe-doped polypyrrole conductive particles could form uniform and dense conductive layers on the BC nanofiber surfaces. These two metal salt oxidants demonstrated differences in the binding sites between PPy and BC.

Speckle noise suppression method in a holographic display based on pixel processing.

In this paper, we propose a method to suppress the speckle noise in a holographic display based on pixel processing. Through the separation of object pixels in space, the recorded object is divided into multiple object point groups. The complex amplitude of the light field for each object point group is recorded as a sub-computer-generated hologram (sub-CGH). The phase of each pixel on a sub-CGH is optimized to generate the final sub-CGH. Therefore, the pixels of the recorded object and sub-CGH are processed. In the reconstruction process, the final sub-CGHs are loaded on the spatial light modulator sequentially. The speckle noise of the reconstructed image is suppressed by reducing the algorithm error and the overlapping area of adjacent image points. The experimental results prove the feasibility of the proposed method.

Clonal integration of stress signal induces morphological and physiological response of root within clonal network.

Clonal integration of defense or stress signal induced systemic resistance in leaf of interconnected ramets. However, similar effects of stress signal in root are poorly understood within clonal network. Clonal fragments of Centella asiaticas with first-young, second-mature, third-old and fourth-oldest ramets were used to investigate transportation or sharing of stress signal among interconnected ramets suffering from low water availability. Compared with control, oxidative stress in root of the first-young, second-mature and third-old ramets was significantly alleviated by exogenous ABA application to the fourth-oldest ramets as well as enhancement of antioxidant enzyme (SOD, POD, CAT and APX) activities and osmoregulation ability. Surface area and volume in root of the first-young ramets were significantly increased and total length in root of the third-old ramets was significantly decreased. POD activity in root of the fourth-oldest and third-old ramets was significantly enhanced by exogenous ABA application to the first-young ramets. Meanwhile, total length and surface area in root of the fourth-oldest and third-old ramets were significantly decreased. Ratio of belowground to aboveground biomass in the whole clonal fragments was significantly increased by exogenous ABA application to the fourth-oldest or first-young ramets. It is suggested that transportation or sharing of stress signal may induce systemic resistance in root of interconnected ramets. Specially, transportation or sharing of stress signal against phloem flow was observed in the experiment. Possible explanation is that rapid recovery of foliar photosynthesis in first-young ramets subjected to exogenous ABA application can partially reverse phloem flow within clonal network. Thus, our experiment provides insight into ecological implication on clonal integration of stress signal.

Ferrocene-functionalized zirconium-oxo clusters for achieving high-performance thermocatalytic redox reactions.

The Zr(IV) ions are easily hydrolyzed to form oxides, which severely limits the discovery of new structures and applications of Zr-based compounds. In this work, three ferrocene (Fc)-functionalized Zr-oxo clusters (ZrOCs), Zr9Fc6, Zr10Fc6 and Zr12Fc8 were synthesized through inhibiting the hydrolysis of Zr(IV) ions, which show increased nuclearity and regular structural variation. More importantly, these Fc-functionalized ZrOCs were used as heterogeneous catalysts for the transfer hydrogenation of levulinic acid (LA) and phenol oxidation reactions for the first time, and displayed outstanding catalytic activity. In particular, Zr12Fc8 with the largest number of Zr active sites and Fc groups can achieve > 95% yield for LA-to-γ-valerolactone within 4 h (130 °C) and > 98% yield for 2,3,6-trimethylphenol-to-2,3,5-trimethyl-p-benzoquinone within 30 min (80 °C), showing the best catalytic performance. Catalytic characterization combined with theory calculations reveal that in the Fc-functionalized ZrOCs, the Zr active sites could serve as substrate adsorption sites, while the Fc groups could act as hydrogen transfer reagent or Fenton reagent, and thus achieve effectively intramolecular metal-ligand synergistic catalysis. This work develops functionalized ZrOCs as catalysts for thermal-triggered redox reactions.

Xianglian Pill combined with 5-fluorouracil enhances antitumor activity and reduces gastrointestinal toxicity in gastric cancer by regulating the p38 MAPK/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Perioperative or postoperative adjuvant chemotherapy based on 5-fluorouracil (5-FU) is a common first-line adjuvant therapy for gastric cancer (GC). However, drug resistance and the side effects of 5-FU have reduced its efficacy. Among these side effects, gastrointestinal (GI) toxicity is one of the most common. Xianglian Pill (XLP) is a Chinese patent medicine that is commonly used for the treatment of diarrhoea. It can reduce inflammation and has a protective effect on the intestinal mucosa. Recent studies have shown that many components of XLP can inhibite tumor cell growth. However, the therapeutic effect of XLP in combination with 5-FU on GC is unclear. AIM OF THE STUDY: To investigate whether the combination of XLP and 5-FU can enhance anti-GC activity while reducing GI toxicity. MATERIALS AND METHODS: XLP was administered orally during intraperitoneal injection of 5-FU in GC mice model. Mice were continuously monitored for diarrhea and xenograft tumor growth. After 2 weeks, the mice were sacrificed and serum was collected to determine interleukin-6 levels. Pathological changes, the expression of pro-inflammatory factors and p38 mitogen-activated protein kinase (MAPK) in GI tissue were determined by Western blot analysis. Pathological changes, apoptosis levels and p38 MAPK expression levels in xenograft tissues were also determined. RESULTS: The results showed that XLP could alleviate GI mucosal injury caused by 5-FU, alleviated diarrhea, and inhibited the expression of nuclear factor (NF)-κB and myeloid differentiation primary response-88. Besides, XLP could promote the 5-FU-induced apoptosis of GC cells and enhance the inhibitory effect of 5-FU on tumor xenografts. Further study showed that XLP administration could regulate the expression of p38 MAPK. CONCLUSIONS: XLP in combination with 5-FU could alleviate its GI side effects and enhance its inhibitory effect on xenograft tumor. Moreover, these effects were found to be related to the regulation of the p38 MAPK/NF-κB pathway.

Natural products for combating multidrug resistance in cancer.

Cancer cells frequently develop resistance to chemotherapeutic therapies and targeted drugs, which has been a significant challenge in cancer management. With the growing advances in technologies in isolation and identification of natural products, the potential of natural products in combating cancer multidrug resistance has received substantial attention. Importantly, natural products can impact multiple targets, which can be valuable in overcoming drug resistance from different perspectives. In the current review, we will describe the well-established mechanisms underlying multidrug resistance, and introduce natural products that could target these multidrug resistant mechanisms. Specifically, we will discuss natural compounds such as curcumin, resveratrol, baicalein, chrysin and more, and their potential roles in combating multidrug resistance. This review article aims to provide a systematic summary of recent advances of natural products in combating cancer drug resistance, and will provide rationales for novel drug discovery.

Low-Frequency Ultrasound Sensitive Piezo1 Channels Regulate Keloid-Related Characteristics of Fibroblasts.

Keloids are benign fibroproliferative tumors that severely diminish the quality of life due to discomfort, dysfunction, and disfigurement. Recently, ultrasound technology as a noninvasive adjuvant therapy is developed to optimize treatment protocols. However, the biophysical mechanisms have not yet been fully elucidated. Here, it is proposed that piezo-type mechanosensitive ion channel component 1 (Piezo1) plays an important role in low-frequency sonophoresis (LFS) induced mechanical transduction pathways that trigger downstream cellular signaling processes. It is demonstrated that patient-derived primary keloid fibroblasts (PKF), NIH 3T3, and HFF-1 cell migration are inhibited, and PKF apoptosis is significantly increased by LFS stimulation. And the effects of LFS is diminished by the application of GsMTx-4, the selective inhibitor of Piezo1, and the knockdown of Piezo1. More importantly, the effects of LFS can be imitated by Yoda1, an agonist of Piezo1 channels. Establishing a patient-derived xenograft keloid implantation mouse model further verified these results, as LFS significantly decreased the volume and weight of the keloids. Moreover, blocking the Piezo1 channel impaired the effectiveness of LFS treatment. These results suggest that LFS inhibits the malignant characteristics of keloids by activating the Piezo1 channel, thus providing a theoretical basis for improving the clinical treatment of keloids.