Paris polyphylla ethanol extract and polyphyllin I ameliorate adenomyosis by inhibiting epithelial-mesenchymal transition.

BACKGROUND: The active ingredients of the Chinese medical herb Paris polyphylla, P. polyphylla ethanol extract (PPE) and polyphyllin I (PPI), potentially inhibit epithelial-mesenchymal transition (EMT) in tumors. However, the roles of these ingredients in inhibiting EMT in adenomyosis (AM) remain to be explored. PURPOSE: The primary goal of the study was to uncover the underlying molecular processes through which PPE and PPI suppress EMT in AM, alongside assessing the safety profiles of these substances. METHODS: To assess the suppressive impact of PPE on adenomyosis-derived cells (AMDCs), we employed Transwell and wound healing assays. The polyphyllins (PPI, PPII, PPVII) contained in PPE were characterized using high-performance liquid chromatography (HPLC). Then, bioinformatics techniques were performed to pinpoint potential PPI targets that could be effective in treating AM. Immunoblotting was used to verify the key proteins and pathways identified via bioinformatics. Furthermore, we examined the efficacy of PPE and PPI in treating Institute of Cancer Research (ICR) mice with AM by observing the morphological and pathological features of the uterus and performing immunohistochemistry. In addition, we assessed safety by evaluating liver, kidney and spleen pathologic features and serum test results. RESULTS: Three major polyphyllins of PPE were revealed by HPLC, and PPI had the highest concentration. In vitro experiments indicated that PPE and PPI effectively prevent AMDCs invasion and migration. Bioinformatics revealed that the primary targets E-cadherin, N-cadherin and TGFß1, as well as the EMT biological process, were enriched in PPI-treated AM. Immunoblotting assays corroborated the hypothesis that PPE and PPI suppress the TGFß1/Smad2/3 pathway in AMDCs to prevent EMT from progressing. Additionally, in vivo studies showed that PPE (3 mg/kg and 6 mg/kg) and PPI (3 mg/kg and 6 mg/kg), successfully suppressed the EMT process through targeting the TGFß1/Smad2/3 signaling pathway. Besides, it was observed that lower doses of PPE (3 mg/kg) and PPI (3 mg/kg) exerted minimal effects on the liver, kidneys, and spleen. CONCLUSIONS: PPE and PPI efficiently impede the development of EMT by inhibiting the TGFß1/Smad2/3 pathway, revealing an alternative pathway for the pharmacological treatment of AM.

Indole Propionic Acid Disturbs the Normal Function of Tryptophanyl-tRNA Synthetase in Mycobacterium tuberculosis.

Tuberculosis (TB) is the leading infectious disease caused by Mycobacterium tuberculosis and the second-most contagious killer after COVID-19. The emergence of drug-resistant TB has caused a great need to identify and develop new anti-TB drugs with novel targets. Indole propionic acid (IPA), a structural analog of tryptophan (Trp), is active against M. tuberculosis in vitro and in vivo. It has been verified that IPA exerts its antimicrobial effect by mimicking Trp as an allosteric inhibitor of TrpE, which is the first enzyme in the Trp synthesis pathway of M. tuberculosis. However, other Trp structural analogs, such as indolmycin, also target tryptophanyl-tRNA synthetase (TrpRS), which has two functions in bacteria: synthesis of tryptophanyl-AMP by catalyzing ATP + Trp and producing Trp-tRNATrp by transferring Trp to tRNATrp. So, we speculate that IPA may also target TrpRS. In this study, we found that IPA can dock into the Trp binding pocket of M. tuberculosis TrpRS (TrpRSMtb), which was further confirmed by isothermal titration calorimetry (ITC) assay. The biochemical analysis proved that TrpRS can catalyze the reaction between IPA and ATP to generate pyrophosphate (PPi) without Trp as a substrate. Overexpression of wild-type trpS in M. tuberculosis increased the MIC of IPA to 32-fold, and knock-down trpS in Mycolicibacterium smegmatis made it more sensitive to IPA. The supplementation of Trp in the medium abrogated the inhibition of M. tuberculosis by IPA. We demonstrated that IPA can interfere with the function of TrpRS by mimicking Trp, thereby impeding protein synthesis and exerting its anti-TB effect.

The mode and timing of administrating nutritional treatment of critically ill elderly patients in intensive care units: a multicenter prospective study.

Introduction: Critically ill patients are more susceptible to malnutrition due to their severe illness. Moreover, elderly patients who are critically ill lack specific nutrition recommendations, with nutritional care in the intensive care units (ICUs) deplorable for the elderly. This study aims to investigate nutrition treatment and its correlation to mortality in elderly patients who are critically ill in intensive care units. Method: A multiple-center prospective cohort study was conducted in China from 128 intensive care units (ICUs). A total of 1,238 elderly patients were included in the study from 26 April 2017. We analyzed the nutrition characteristics of elderly patients who are critically ill, including initiated timing, route, ways of enteral nutrition (EN), and feeding complications, including the adverse aspects of feeding, acute gastrointestinal injury (AGI), and feeding interruption. Multivariate logistic regression analysis was used to screen out the impact of nutrition treatment on a 28-day survival prognosis of elderly patients in the ICU. Result: A total of 1,238 patients with a median age of 76 (IQR 70-83) were enrolled in the study. The Sequential Organ Failure (SOFA) median score was 7 (interquartile range: IQR 5-10) and the median Acute Physiology and Chronic Health Evaluation (APACHE) II was 21 (IQR 16-25). The all-cause mortality score was 11.6%. The percentage of nutritional treatment initiated 24 h after ICU admission was 58%, with an EN of 34.2% and a parenteral nutrition (PN) of 16.0% in elderly patients who are critically ill. Patients who had gastrointestinal dysfunction with AGI stage from 2 to 4 were 25.2%. Compared to the survivors' group, the non-survivors group had a lower ratio of EN delivery (57% vs. 71%; p = 0.015), a higher ratio of post-pyloric feeding (9% vs. 2%; p = 0.027), and higher frequency of feeding interrupt (24% vs. 17%, p = 0.048). Multivariable logistics regression analysis showed that patients above 76 years old with OR (odds ratio) 2.576 (95% CI, 1.127-5.889), respiratory rate > 22 beats/min, and ICU admission for 24 h were independent risk predictors of the 28-day mortality study in elderly patients who are critically ill. Similarly, other independent risk predictors of the 28-day mortality study were those with an OR of 2.385 (95%CI, 1.101-5.168), lactate >1.5 mmol/L, and ICU admission for 24 h, those with an OR of 7.004 (95%CI, 2.395-20.717) and early PN delivery within 24 h of ICU admission, and finally those with an OR of 5.401 (95%CI, 1.175-24.821) with EN delivery as reference. Conclusion: This multi-center prospective study describes clinical characteristics, the mode and timing of nutrition treatment, frequency of AGI, and adverse effects of nutrition in elderly ICU patients. According to this survey, ICU patients with early PN delivery, older age, faster respiratory rate, and higher lactate level may experience poor prognosis.

Anti-rheumatoid arthritis potential of different fractions derived from of Coluria longifolia.

Coluria longifolia Maxim (C. longifolia) is a Chinese folk medication commonly used to treat arthritis and joint pain. Literatures have reported that C. longifolia has significant anti-inflammatory, analgesic and antipyretic effects. The aim of this research was to assay the effective fractions of C. longifolia (EFCL) against rheumatoid arthritis (RA) and to elucidate its anti-RA mechanism on a preliminary basis. The rat model of collagen-induced arthritis (CIA) was established. The therapeutic effects of different fractions in vivo were evaluated by body weight changes, a foot swelling score, inflammatory factors and histopathological examination. The mechanism of EFCL was investigated by activity of oxidative stress related enzyme, qPCR and Western blotting tests. In vivo results showed that total extraction (TE) and n-butanol fraction (NF) could significantly alleviate the symptoms of RA, decrease the levels of IL-6 and TNF-α (P < 0.01), and improve histopathological injury. The mechanism study showed that SOD level was significantly increased with MDA level decreased in the NF group. The upregulated proteins and mRNA expression levels of Nrf2, HO1 and NQO1 after TE and NF administration suggested that the anti-arthritic effect may be related to the Nrf2 signaling pathway and downstream HO1 and NQO1. In conclusion, this study confirmed that C. longifolia is capable of treating RA with NF as the main effective fraction. Its anti-RA action may be associated with Nrf2 signaling pathway and downstream HO1 and NQO1.

Using ultra-performance liquid chromatography with linear ion trap-electrostatic field orbitrap mass spectrometry, network pharmacology, and molecular docking to explore the constituent targets and action mechanisms of decoction of Angelica sinensis, Zingiberis Rhizoma Recens, and Mutton in the treatment of diarrhea-predominant irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic intestinal disorder characterized by abdominal discomfort, stool characteristics, and changes in bowel habits. Among them, diarrhea-type (diarrhea-predominant irritable bowel syndrome, abbreviated as IBS-D) is the most common. Because its pathogenesis is not understood, symptomatic treatment is currently used in clinical practice, and its long-term effect is still unclear. Decoction of Angelica sinensis, Zingiberis Rhizoma Recens, and Mutton (DAZM) is a famous traditional Chinese medicine recipe created by Zhang Zhongjing, a famous doctor in the Eastern Han Dynasty 2000 years ago, and is still in use today. Our research team has previously investigated the clinical study of DAZM in the treatment of IBS-D and conducted animal experiment research, indicating that DAZM has a significant effect on improving IBS-D. Yet, there are few reports on the specific mechanism of action of DAZM in improving the treatment of IBS and related types. Most studies discuss and verify its efficacy and protection from a clinical perspective. For this reason, this research will explore the constituent targets and mechanisms of DAZM to improve the treatment of IBS-D, provide relevant scientific evidence, and also provide reference evidence for the efficacy of food therapy decoction in improving the treatment of diseases and mechanism to open up new experimental research ideas. METHODS: Identification of drug ingredients and collection of targets for DAZM using ultra-performance liquid chromatography with linear ion trap-electrostatic field orbitrap mass spectrometry and the Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine database, active ingredients were selected based on their oral bioavailability and drug-like properties. Obtained IBS-D targets using the GeneCards database, took the intersection of IBS-D targets and DAZM targets and obtained potential targets of DAZM for the treatment of IBS-D. Using Cytoscape software to draw a network diagram of "Food therapy decoction-ingredient-target-disease" and selected the ingredients with larger parameter values by topological analysis. Correlation analysis of the selected active and parametric ingredients with prominent symptoms of IBS-D using SymMap database, and selection of potential core ingredients. The construction of protein interaction networks from the String database and the selection of potential core targets. Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes signaling pathway enrichment analyses using the Metascape database, establishing the bioinformatic processes and signaling pathways involved. Molecular docking of core ingredients and potential core targets was performed using AutoDock Vina, and the results were visualized using Python molecule (PyMOL) and LigPlus+. Finally, based on the results of this research combined with previous literature reports, the discussion section of this paper summarizes in detail the key core ingredients, targets, and signaling pathways of DAZM in improving IBS-D. RESULTS: DAZM may act on eight potential core targets (threonine kinase 1, insulin, tumour necrosis factor, tumour protein p53, interleukin 6, epidermal growth factor receptor, connexin ß1, and interleukin 1ß) through eight core ingredients (Zingiberone, Shyobunone, Palmitic acid, Sebiferic acid, ß-Bisabolene, ß-Sitosterol, Stigmasterol, and Oleic acid). inhibit pro-inflammatory factors through Advanced Glycation End Products-Receptor (AGE-RAGE) signaling pathway, Cyclic Adenosine Monophosphate (cAMP) signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, Calmodulin (CaM) signaling pathway, and other pathways. It can alleviate the inflammatory response, enhance the intestinal mucosal barrier and regulate intestinal motility, and play a role in the treatment and improvement of IBS-D. CONCLUSIONS: This research mainly found the mechanism of DAZM on IBS-D, which may involve multiple ingredients, multiple targets, and multiple pathways. DAZM with medicinal and edible functions can effectively improve the treatment of IBS-D. This kind of dietary therapy is suitable for long-term treatment and is worthy of promotion.

Thermosensitive black phosphorus hydrogel loaded with silver sulfadiazine promotes skin wound healing.

Wounds can lead to skin and soft tissue damage and their improper management may lead to the growth of pathogenic bacteria at the site of injury. Identifying better ways to promote wound healing is a major unmet need and biomedical materials with the ability to promote wound healing are urgently needed. Here, we report a thermosensitive black phosphorus hydrogel composed of black phosphorus nano-loaded drug silver sulfadiazine (SSD) and chitosan thermosensitive hydrogel for wound healing. The hydrogel has temperature-sensitive properties and enables the continuous release of SSD under near-infrared irradiation to achieve synergistic photothermal and antibacterial treatment. Additionally, it exerts antibacterial effects on Staphylococcus aureus. In a rat skin injury model, it promotes collagen deposition, boosts neovascularization, and suppresses inflammatory markers. In summary, the excellent thermosensitivity, biocompatibility, and wound-healing-promoting qualities of the reported thermosensitive hydrogel make it suitable as an ideal wound dressing in the clinic.

Factors associated with the incidence and the expenditure of self-medication among middle-aged and older adults in China: A cross-sectional study.

Background: With the accelerated ageing of population and the growing prevalence of various chronic diseases in China, self-medication plays an increasingly important role in complementing the health care system due to its convenience and economy. Objective: This study aimed to investigate the incidence of self-medication and the amount of self-medication expenditure among middle-aged and older adults in China, and to explore factors associated with them. Methods: A total of 10,841 respondents aged 45 years and older from the China Health and Retirement Longitudinal Study (CHARLS) wave 4 which conducted in 2018 were included as the sample of this study. The two-part model was adopted to identify the association between the incidence of self-medication and the amount of self-medication expenditure and specific factors, respectively. Results: The incidence of self-medication among Chinese middle-aged and older adults was 62.30%, and the average total and out-of-pocket (OOP) pharmaceutical expenditure of self-medication of the self-medicated individuals were 290.50 and 264.38 Chinese yuan (CNY) respectively. Participants who took traditional Chinese medicine (TCM), self-reported fair, and poor health status, suffered from one and multiple chronic diseases had strongly higher incidence of self-medication. Older age and multiple chronic diseases were strongly associated with higher expenditure of self-medication. Those who took TCM had more self-medication expenditure, while those who drank alcohol had less. Conclusion: Our study demonstrated the great prevalence of self-medication among middle-aged and older adults in China and the large pharmaceutical expenditure that come with it, especially in the high-risk groups of self-medication identified in this paper. These findings enhanced our understanding of self-medication behaviors among Chinese middle-aged and older adults and may contribute to the formulation of targeted public health policy.

Exploring the mechanism of an active ingredient of ginger, dihydrocapsaicin, on triple negative breast cancer based on network pharmacology and in vitro experiments.

To investigate the potential mechanism of ginger in the treatment of triple-negative breast cancer (TNBC) based on network pharmacology, molecular docking and in vitro cell experiments. The Traditional Chinese Medicine Systems Pharmacology Database And Analysis Platform, the Bioinformatics Analysis Tool For Molecular Mechanism Of Traditional Chinese Medicine and the HERB database and literature search were used to search for the main active compounds of ginger. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were used to predict the possible molecular mechanism and signaling pathway of ginger in the treatment of triple negative breast cancer. The key core genes of ginger in the treatment of triple negative breast cancer were docked with the active ingredients of ginger on the Autodock platform, and the mechanism of ginger on triple negative breast cancer was further verified by in vitro cell experiments. As a result, 10 effective components, 27 potential targets and 10 Protein-Protein Interaction core genes were predicted in the treatment of triple negative breast cancer with ginger, involving 287 biological processes, 18 cellular components and 38 molecular functions. Ginger regulated the proliferation, migration and apoptosis of triple negative breast cancer cells by regulating TNF, IL-17, FoxO, MAPK, PI3K/AKT and other signaling pathways. The results of molecular docking showed that the lowest binding potential energy between dihydrocapsaicin (DHC) and EGFR protein was -7.70 kcal·mol-1, followed by that between 6-gingerol and EGFR protein was -7.30 kcal·mol-1 and that between DHC and CASP3 protein was -7.20 kcal·mol-1. In vitro cell experiments showed that ginger could inhibit the proliferation and migration of TNBC MDA-MB-231 cells, increase the mRNA expression of Caspase family CASP9 and the protein expression of CASP3 and BAX. Overall, based on the combination of network pharmacology and in vitro cell experiments, ginger has the characteristics of multi-target in the treatment of TNBC, which may play a regulatory role through the PI3K/AKT family. It provides a reference for the drug development of ginger and the clinical treatment of triple negative breast cancer.

Analysis of the Mechanism of GuizhiFuling Wan in Treating Adenomyosis Based on Network Pharmacology Combined with Molecular Docking and Experimental Verification.

Background: The effect of GuizhiFuling Wan (GFW) on adenomyosis (AM) is definite. This study aimed to explore the mechanism and key therapeutic targets of GFW in treating AM through network pharmacology combined with molecular docking and experimental verification. Materials and Methods: In network pharmacology, firstly, the active components of GFW, its drug, and disease targets were screened through several related public databases, and GFW-AM common targets were obtained after the intersection. Then, the biological function (Gene Ontology, GO) and pathway (Kyoto Encyclopedia of Genes and Genomes, KEGG) of GFW in treating AM were enriched and analyzed. Finally, the interaction and binding force between key components and key targets of GFW were verified by molecular docking. In the animal part, the effect of GFW on the expression of matrix metallopeptidase 2 (MMP-2), matrix metallopeptidase 9 (MMP-9), and vascular endothelial growth factor (VEGF) in mice with AM was observed by HE staining, ELISA, and immunohistochemistry. Results: In this study, 89 active components of GFW, 102 related targets, and 291 targets of AM were collected. After the intersection, 26 common targets were finally obtained. The key active compounds were baicalein, sitosterol, and ß-sitosterol, and the key targets were MMP-2, MMP-9, and VEGF. GO and KEGG enrichment analyses showed that biological processes such as the positive regulation of vascular endothelial migration and signaling pathways such as TNF and HIF-1 were involved in regulating angiogenesis, invasion, and metastasis in AM. The molecular docking results showed that baicalein, ß-sitosterol, and stigmasterol had better binding potential with MMP-2, MMP-9, and VEGF. The results of in vivo analysis showed that GFW could decrease the serum content and protein expression of MMP-2, MMP-9, and VEGF in mice with AM. Conclusions: GFW could reduce the expression of MMP-2, MMP-9, and VEGF, which might be an essential mechanism for GFW to inhibit the invasion and metastasis of ectopic tissues of AM.

Sorafenib-Loaded Cu2-xSe Nanoparticles Boost Photothermal-Synergistic Targeted Therapy against Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) accounts for the predominant form of liver malignancy and presents a leading cause of cancer-related death globally. Sorafenib (SOR), a first-line targeted drug for advanced HCC treatment, has a battery of untoward side effects. Photothermal therapy (PTT) has been utilized as an effective adjuvant in synergy with other approaches. However, little is known about the tumoricidal efficacy of combining SOR with PTT for HCC. Herein, a novel versatile nanoparticle, Cu2-xSe@SOR@PEG (CSP), that is based on a photothermal Cu2-xSe core and SOR for simultaneously reinforcing PTT and reducing the adverse effects of SOR was constructed. The synthesized CSP exhibited a remarkably enhanced therapeutic effect upon 808 nm laser irradiation via dampening HCC cell propagation and metastasis and propelling cell apoptosis. The intravenous administration of CSP substantially suppressed tumor growth in a xenograft tumor mouse model. It was noted that the CSP manifested low toxicity and excellent biocompatibility. Together, this work indicates a promising and versatile tool that is based on synergistic PTT and molecular-targeted therapy for HCC management.

Iridium Complex-Loaded Sorafenib Nanocomposites for Synergistic Chemo-photodynamic Therapy of Hepatocellular Carcinoma.

Although sorafenib, a multi-kinase inhibitor, has provided noteworthy benefits in patients with hepatocellular carcinoma (HCC), the inevitable side effects, narrow therapeutic window, and low bioavailability seriously affect its clinical application. To be clinically distinctive, innovative drugs must meet the needs of reaching tumor tissues and cause limited side effects to normal organs and tissues. Recently, photodynamic therapy, utilizing a combination of a photosensitizer and light irradiation, was selectively accumulated at the tumor site and taken up effectively via inducing apoptosis or necrosis of cancer cells. In this study, a nano-chemo-phototherapy drug was fabricated to compose an iridium-based photosensitizer combined with sorafenib (IPS) via a self-assembly process. Compared to the free iridium photosensitizer or sorafenib, the IPS exhibited significantly improved therapeutic efficacy against tumor cells because of the increased cellular uptake and the subsequent simultaneous release of sorafenib and generation of reactive oxygen species production upon 532 nm laser irradiation. To evaluate the effect of synergistic treatment, cytotoxicity detection, live/dead staining, cell proliferative and apoptotic assay, and Western blot were performed. The IPS exhibited sufficient biocompatibility by hemolysis and serum biochemical tests. Also, the results suggested that IPS significantly inhibited HCC cell proliferation and promoted cell apoptosis. More importantly, marked anti-tumor growth effects via inhibiting cell proliferation and promoting tumor cell death were observed in an orthotopic xenograft HCC model. Therefore, our newly proposed nanotheranostic agent for combined chemotherapeutic and photodynamic therapy notably improves the therapeutic effect of sorafenib and has the potential to be a new alternative option for HCC treatment.

Mechanism Study of Cinnamomi Ramulus and Paris polyphylla Sm. Drug Pair in the Treatment of Adenomyosis by Network Pharmacology and Experimental Validation.

Objective: To explore the molecular mechanism of the Cinnamomi ramulus and Paris polyphylla Sm. (C-P) drug pair in the treatment of adenomyosis (AM) based on network pharmacology and animal experiments. Methods: Via a network pharmacology strategy, a drug-component-target-disease network (D-C-T-D) and protein-protein interaction (PPI) network were constructed to explore the core components and key targets of C-P drug pair therapy for AM, and the core components and key targets were verified by molecular docking. Based on the results of network pharmacology, animal experiments were performed for further verification. The therapeutic effect of the C-P drug pair on uterine ectopic lesions was evaluated in a constructed AM rat model. Results: A total of 30 components and 45 corresponding targets of C-P in the treatment of AM were obtained through network pharmacology. In the D-C-T-D network and PPI network, 5 core components and 10 key targets were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the PI3K signaling pathway was the most significantly enriched nontumor pathway. Molecular docking showed that most of the core components and key targets docked completely. Animal experiments showed that the C-P drug pair significantly ameliorated the pathological changes of endometriotic lesions in AM model rats and inhibited PI3K and Akt gene expression, and PI3K and Akt protein phosphorylation. In addition, treatment with the C-P drug pair promoted AM cell apoptosis; upregulated the protein expression of Bax, Caspase-3, and cleaved Caspase-9; and restrained Bcl-2 expression. Conclusions: We propose that the pharmacological mechanism of the C-P drug pair in the treatment of AM is related to inhibition of the PI3K/Akt pathway and promotion of apoptosis in AM ectopic lesions.

Long circulation and tumor-targeting biomimetic nanoparticles for efficient chemo/photothermal synergistic therapy.

Photothermal therapy combined with chemotherapy based on nanomedicine has been considered a promising strategy for improving therapeutic efficacy in a tumor. However, nanomedicine can be easily cleared by the immune system without specific surface engineering modifications, thus affecting the ultimate efficacy. Herein, multifunctional biomimetic nanoparticles (Bio-RBCm@PDA@MSN-DOX) with enhanced long circulation and targeting ability are constructed by coating large pore-sized mesoporous silica (MSN) with polydopamine (PDA) layers in a biotin modified red blood cell membrane (Bio-RBCm) for efficient chemo/photothermal synergistic therapy. It is demonstrated that Bio-RBCm@PDA@MSN-DOX presents high photothermal conversion efficiency (40.17%) and enhanced capability to accelerate the release of the anticancer drug (doxorubicin, DOX), thus showing a good synergistic therapeutic effect in cell experiments. More importantly, with the assistance of the biotin and RBC membrane, Bio-RBCm@PDA@MSN-DOX can successfully evade immune clearance and effectively target transport to HeLa tumor sites, finally accomplishing up to 98.95% tumor inhibition with negligible side effects to normal tissues. This multilayer structure presents a valuable model for future therapeutic applications with safe and effective tumor chemotherapy and photothermal therapy.

Solar-assisted high-efficient cleanup of viscous crude oil spill using an ink-modified plant fiber sponge.

Rapid and efficient clean-up of viscous crude oil spills is still a global challenge due to its high viscous and poor flowability at room temperature. The hydrophobic/oleophilic absorbents with three-dimensional porous structure have been considered as a promising candidate to handle oil spills. However, they still have limited application in recovering the high viscous oil. Inspired by the viscosity of crude oil depended on the temperature, a solar-heated ink modified plant fiber sponge (PFS@GC) is fabricated via a simple and environmentally friendly physical foaming strategy combined with in-situ ink coating treatment. After wrapping by the polydimethylsiloxane (PDMS), the modified PFS@GC (PFS@GC@PDMS) exhibits excellent compressibility, high hydrophobic (141° in water contact angle), solar absorption (> 96.0%), and oil absorptive capacity (12.0-27.8 g/g). Benefiting from the favorable mechanical property and photothermal conversion capacity, PFS@GC@PDMS is demonstrated as a high-performance absorbent for crude oil clean-up and recovery. In addition, PFS@GC@PDMS can also be applied in a continuous absorption system for uninterrupted recovering of oil spills on the water surface. The proposed solar-heated absorbent design provides a new opportunity for exploring biomass in addressing large-scale oil spill disasters.

Studies on the Mechanism of the Volatile Oils from Caoguo-4 Decoction in Regulating Spleen Deficiency Diarrhea by Adjusting Intestinal Microbiota.

BACKGROUND: The Caoguo-4 decoction, a classical Mongolian medicine formula, is widely used to treat spleen deficiency diarrhea (SDD) in Mongolian for decades. Previously, the Caoguo-4 decoction volatile oil has been confirmed to be effective in ameliorating symptoms of spleen deficiency diarrhea in an animal model. However, the underlying mechanism of the Caoguo-4 decoction volatile oil is yet to be established. The aim of the current study was to investigate the antidiarrheal effects and mechanism of the Caoguo-4 decoction volatile oil. METHOD: Wistar rats were randomly divided into 5 groups of 10 animals including control, model, positive, Caoguo-4 decoction, and Caoguo-4 decoction volatile oil groups (10 rats in each group). All the rats, besides those in the control group, were induced to develop SDD by a bitter-cold purgation method with Xiaochengqi decoction. The antidiarrheal effect of Caoguo-4 decoction volatile oil was evaluated by pathological section, serum D-xylose and AMS content, plasma MTL content, and gut microbiota analysis via 16S rRNA sequencing. RESULTS: The results showed that the developed SDD rat model (model group) had decreased food intake, increased weight loss, soft stool, and bad hair color. When compared with the control group, serum was significantly reduced serum D-xylose and AML but increased MTL levels in the model group (p < 0.05). However, after treatment with either the Caoguo-4 decoction (the decoction group) or Smecta (the positive group) or volatile oil from the Caoguo-4 decoction (the volatile oil group), a significant increase in the serum D-xylose levels was observed. Additionally, AML levels significantly increased in the positive and volatile oil groups, and MTL levels significantly decreased in the decoction and volatile oil groups, when compared with the model group (p < 0.05). The pathological changes of the intestinal mucosa showed that the structure of the epithelium in the villi of the small intestine was affected, deformed, and incomplete in the model group when compared with the control group. However, either the decoction group or the volatile oil group recovered the villous morphology. The results of OTU analysis and alpha diversity analysis of intestinal bacteria showed that the intestinal microbiota of the SDD model rats showed an obvious decrease in richness and diversity of intestinal microbiota. But the intervention treatment of decoction and volatile oil could significantly recover the richness and diversity of intestinal microbiota. CONCLUSION: The intestinal microbiota destroyed in SDD modelling could be significantly improved by the Caoguo-4 decoction volatile oils, which provides reference for clinical medication.

Bioactive constituents of Mosla chinensis-cv. Jiangxiangru ameliorate inflammation through MAPK signaling pathways and modify intestinal microbiota in DSS-induced colitis mice.

BACKGROUND: Mosla chinensis Maxim. cv. Jiangxiangru (JXR), a traditional Chinese medicine, commonly used for the therapy of cold, fever, diarrhea, digestive disorders, and other diseases. Inflammatory bowel disease (IBD) is a chronic disorder of the human gastrointestinal tract. Research about the effect of JXR on IBD and the active ingredient composition of JXR remains deficiency. PURPOSE: This study aims to determine the phytochemical composition and the anti-inflammatory property of JXR, as well as the possible anti-inflammatory mechanisms. METHODS: The bioactive profile of JXR extracts was determined by UPLC-LTQ-Orbitrap-MS. A DSS induced colitis mouse model was applied to explore the anti-inflammatory activity of JXR. The body weight, colon length and histopathological status of colon tissue were evaluated. The content of inflammatory mediators (nitric oxide (NO), prostaglandin E2 (PGE2)) and cytokines (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß)), corresponding mRNA and protein expression levels were analyzed. Oxidation pressure and gut microbial composition were also explored. RESULTS: Totally 63 constitutes were identified from JXR, among them, phenolic acids and flavonoids comprised a large part, and rosmarinic acid (RA) was the main compound. The results of DSS-induced colitis mice model indicated that JXR effectively ameliorated inflammation, restore the redox balance in the gut. JXR treatment significantly reduced the production of reactive oxygen species (ROS), increased the activity of antioxidative enzyme, suppressed the secretion of inflammatory mediators (NO, PGE2) and cytokines (TNF-α, IL-6, IL-1ß). JXR also restrained the activation of mitogen-activated protein kinases (MAPKs) signaling pathway. Furthermore, JXR could restore the microbial diversity by suppressing Bacteroidaceae, increasing Bifidobacteriales and Melainabacteria in DSS colitis mouse model. CONCLUSIONS: This study demonstrated that JXR composed with various bioactive compounds, effectively ameliorated colitis, restored the redox balance and regulated gut microbiota. Results from the present study provide an insight of therapeutic potential of JXR in IBD based on its anti-inflammatory and antioxidant properties, also provide a scientific basis for using JXR as a functional ingredient to promote colon health.

Engineered Platelet-Based Micro/Nanomotors for Cancer Therapy.

Engineered platelets (PLT) can bring new possibilities for diseases treatment due to the specific response for a variety of physiological disease environments. However, the deep penetration of engineered PLT in diseased tissues such as tumor is still an important challenge that restricts the therapeutic effect. Herein, the engineered PLT micromotor (PLT@PDA-DOX) is constructed by a universal self-polymerization modification method of dopamine, and the chemotherapeutic drug doxorubicin (DOX) is loaded by both π-π stacking interaction with polydopamine (PDA) and cellular endocytosis of PLT. The experimental results prove that PLT@PDA-DOX can target to tumor site by the specific binding of PLT with cancer cells, and then the secondary PLT-derived microparticles (PMP@PDA-DOX) are released with the activation of PLT@PDA-DOX by tumor microenvironment (TME). Besides, benefiting from the photothermal conversion capability of PDA, PLT@PDA-DOX micromotors and PMP@PDA-DOX nanomotors are driven by near-infrared light to realize deep penetration. And the PLT-based micro/nanomotors with propulsion capability possess good performance for tumor ablating in vitro and in vivo. In consideration of the operability, mildness, universality of this modification method and the good biocompatibility of PDA, this work may provide a general paradigm for the construction of engineered cells in disease treatment.

Mechanosensitive TRPV4 is required for crystal-induced inflammation.

Crystal structures activate innate immune cells, especially macrophages and initiate inflammatory responses. We aimed to understand the role of the mechanosensitive TRPV4 channel in crystal-induced inflammation. Real-time RT-PCR, RNAscope in situ hybridisation, and Trpv4eGFP mice were used to examine TRPV4 expression and whole-cell patch-clamp recording and live-cell Ca2+ imaging were used to study TRPV4 function in mouse synovial macrophages and human peripheral blood mononuclear cells (PBMCs). Both genetic deletion and pharmacological inhibition approaches were used to investigate the role of TRPV4 in NLRP3 inflammasome activation induced by diverse crystals in vitro and in mouse models of crystal-induced pain and inflammation in vivo. TRPV4 was functionally expressed by synovial macrophages and human PBMCs and TRPV4 expression was upregulated by stimulation with monosodium urate (MSU) crystals and in human PBMCs from patients with acute gout flares. MSU crystal-induced gouty arthritis were significantly reduced by either genetic ablation or pharmacological inhibition of TRPV4 function. Mechanistically, TRPV4 mediated the activation of NLRP3 inflammasome by diverse crystalline materials but not non-crystalline NLRP3 inflammasome activators, driving the production of inflammatory cytokine interleukin-1ß which elicited TRPV4-dependent inflammatory responses in vivo. Moreover, chemical ablation of the TRPV1-expressing nociceptors significantly attenuated the MSU crystal-induced gouty arthritis. In conclusion, TRPV4 is a common mediator of inflammatory responses induced by diverse crystals through NLRP3 inflammasome activation in macrophages. TRPV4-expressing resident macrophages are critically involved in MSU crystal-induced gouty arthritis. A neuroimmune interaction between the TRPV1-expressing nociceptors and the TRPV4-expressing synovial macrophages contributes to the generation of acute gout flares.

Differences in clinical characteristics between younger and older patients with COVID-19 and their relationship with the length of hospital stay.

Background: The coronavirus disease 2019 (COVID-19) pandemic is currently threatening the health of individuals worldwide. We compared the clinical characteristics between younger patients (aged <60 years) and older patients (aged ≥60 years) with COVID-19, detected the risk factors associated with a prolonged hospital stay, and examined the treatments commonly used with a particular focus on antiviral therapies. Methods: This retrospective study was conducted at the West Campus, Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology (Wuhan, China). The sample consisted of 123 patients admitted to the hospital between 9th February, 2020, and 3rd March, 2020. The data related to the demographics, laboratory findings, and treatment were analyzed to identify discrepancies between younger and older patients and those with and without primary diseases. The risk factors that contribute to a prolonged hospital stay were subsequently identified. Results: Patients aged ≥60 years required longer hospital stay than younger patients (P=0.001). The percentage of lymphocytes was significantly lower in older patients and those with primary diseases (P=0.016 and P=0.042, respectively). The findings revealed that the risk factors that contributed to the length of hospital stay were age, the number of days of illness before hospitalization, white blood cell (WBC) count and albumin levels at admission, a neutrophil fraction at discharge, and antibiotic treatment. Analysis using a model that consisted of the above five risk factors for predicting prolonged hospital stay (>14 days) yielded an area under the ROC (AuROC) curve of 0.716. Antiviral and antibiotic treatments were administered to 97.6% and 39.0% of patients, respectively. The antiviral drugs most commonly administered were traditional Chinese medicine (83.7%) and arbidol (75.6%). Conclusions: In this study, older patients and those with primary diseases were at a higher risk of worse clinical manifestations. The physicians who treat the patients should pay close attention to the risk factors that contribute to the length of hospital stay, which could be used for predicting prolonged hospital stay. Traditional Chinese medicine and arbidol were the most frequently used antiviral drugs. Nevertheless, the extent to which these medications can effectively treat COVID-19 warrants further investigation.