Molecular mechanisms of Tetrastigma hemsleyanum Diels&Gilg against lung squamous cell carcinoma: From computational biology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Tetrastigma hemsleyanum （T. hemsleyanum）, valued in traditional medicine for its potential to boost immunity and combat tumors, contains uncharacterized active compounds and mechanisms. This represents a significant gap in our understanding of its ethnopharmacological relevance. AIM OF THE STUDY: To involve the mechanism of anti-lung cancer effect of T. hemsleyanum by means of experiment and bioinformatics analysis. MATERIALS AND METHODS: The anticancer mechanism of T. hemsleyanum against lung squamous carcinoma (LUSC) in zebrafish was investigated. The LUSC model was established by injecting NCI-H2170 cells in the zebrafish and evaluating its anti-tumor efficacy. Next, component targets and key genes were obtained by molecular complex detection (MCODE) analysis and protein-protein interaction (PPI) network analysis. Component analysis of T. hemsleyanum was performed by UPLC-Q-TOF-MS. Molecular docking was used to simulate the binding activities of key potential active components to core targets were simulated using. Prognostic and pan-cancer analyses were then performed to validate the signaling pathways involved in the prognostic genes using gene set enrichment analysis (GSEA). Subsequently, Molecular dynamics simulations were then performed for key active components and core targets. Finally, cellular experiments were used to verify the expression of glutamate metabotropic receptor 3 (GRM3) and glutamate metabotropic receptor 7 (GRM7) in the anticancer effect exerted of T. hemsleyanum. RESULTS: We experimentally confirmed the inhibitory effect of T. hemsleyanum on LUSC by transplantation of NCI-H2170 cells into zebrafish. There are 20 main compounds in T. hemsleyanum, such as procyanidin B1, catechin, quercetin, and kaempferol, etc. A total of 186 component targets of T. hemsleyanum and sixteen hub genes were screened by PPI network and MCODE analyses. Molecular docking and molecular dynamics simulation results showed that Gingerglycolipid B and Rutin had higher affinity with GRM3 and GRM7, respectively. Prognostic analysis, Pan-cancer analysis and verification experiment also confirmed that GRM3 and GRM7 were targets for T. hemsleyanum to exert anti-tumor effects and to participate in immune and mutation processes. In vitro experiments suggested that the inhibitory effect of T. hemsleyanum on cancer cells was correlated with GRM3 and GRM7. CONCLUSION: In vivo, in vitro and in silico results confirmed the potential anticancer effects against LUSC of T. hemsleyanum, which further consolidated the claim of its traditional uses.

Differential impacts of porous starch versus its octenyl succinic anhydride-modified counterpart on naringin encapsulation, solubilization, and in vitro release.

The aim of this work was to evaluate the potentials of porous starch (PS) and its octenyl succinic anhydride modified product (OSAPS) as efficient carriers for loading naringin (NA), focusing on encapsulation efficiency (EE, the percentage of adsorbed naringin relative to its initial amount), drug loading (DL, the percentage of naringin in the complex), structural alterations, solubilization and in vitro release of NA using unmodified starch (UMS) and NA as controls. Both the pore diameter and SBET value of PS decreased after esterification with OSA, and a thinner strip-shaped NA (∼145 nm) was observed in the OSAPS-NA complex and (∼150 nm) in the PS-NA complex. OSAPS exhibited reduced short-range ordered structure, as indicated by a lower R1047/1022 (0.73) compared to PS (0.77). Meanwhile, lowest crystallinity (12.81 %) of NA was found in OSAPS-NA. OSAPS-NA exhibited higher EE and DL for NA than PS-NA and a significant increase in NA saturated solubility in deionized water (by 11.63-fold) and simulated digestive fluids (by 24.95-fold) compared to raw NA. OSAPS contained higher proportions of slowly digestible starch and exhibited a lower digestion rate compared to PS, resulting in a longer time for NA release from its complex during the digestion.

Investigation of the driving voltage on the high performance flexible ATF-ECDs based on PET/ITO/NiOX/LiTaO3/WO3/ITO.

High performance flexible all-thin-film electrochromic devices (ATF-ECDs) have been fabricated and systematically investigated by operating with different driving voltages during the electrochromic processes. The device structure (cross-section) and material properties of some main functional layers were presented and analysed. The electrochromic properties including kinetic and spectral tests were systematically investigated through combining chronoamperometry, cyclic voltammetry measurements and optical measurements. In addition, the open circuit memory measurement was also carried out. A much higher driving voltage might lead to a current leakage inside the device during coloring process. A proper driving voltage is needed for achieving high device performances. More details were widely described and deeply discussed.

Asymmetric copper-catalyzed alkynylallylic monofluoroalkylations with fluorinated malonates.

The unprecedented copper-catalyzed asymmetric alkynylallylic monofluoroalkylation reaction is described via the use of 1,3-enynes and fluorinated malonates. A series of 1,4-enynes bearing a monofluoroalkyl unit are achieved in high yields, excellent regio- and enantioselectivity and high E/Z selectivity. The asymmetric propargylic monofluoroalkylation is also developed. The reliability and synthetic value of the work are highlighted by a gram-scale test and a couple of downstream transformations. Preliminary mechanistic studies unveil a negative nonlinear effect for the catalytic process.

Quercetin as a promising intervention for rat osteoarthritis by decreasing M1-polarized macrophages via blocking the TRPV1-mediated P2X7/NLRP3 signaling pathway.

Osteoarthritis (OA) is characterized by an imbalance between M1 and M2 polarized synovial macrophages. Quercetin has shown protective effects against OA by altering M1/M2-polarized macrophages, but the underlying mechanisms remain unclear. In this study, rat chondrocytes were treated with 10 ng/mL of IL-1ß. To create M1-polarized macrophages in vitro, rat bone marrow-derived macrophages (rBMDMs) were treated with 100 ng/mL LPS. To mimic OA conditions observed in vivo, a co-culture system of chondrocytes and macrophages was established. ATP release assays, immunofluorescence assays, Fluo-4 AM staining, Transwell assays, ELISA assays, and flow cytometry were performed. Male adult Sprague-Dawley (SD) rats were used to create an OA model. Histological analyses, including H&E, and safranin O-fast green staining were performed. Our data showed a quercetin-mediated suppression of calcium ion influx and ATP release, with concurrent downregulation of TRPV1 and P2X7 in the chondrocytes treated with IL-1ß. Activation of TRPV1 abolished the quercetin-mediated effects on calcium ion influx and ATP release in chondrocytes treated with IL-1ß. In the co-culture system, overexpression of P2X7 in macrophages attenuated the quercetin-mediated effects on M1 polarization, migration, and inflammation. Either P2X7 or NLRP3 knockdown attenuated IL-1ß-induced M1/M2 polarization, migration, and inflammation. Moreover, overexpression of TRPV1 reduced the quercetin-mediated suppressive effects on OA by promoting M1/M2-polarized macrophages in vivo. Collectively, our data showed that quercetin-induced suppression of TRPV1 leads to a delay in OA progression by shifting the macrophage polarization from M1 to M2 subtypes via modulation of the P2X7/NLRP3 pathway.

Over 10% Efficient Sb2(S,Se)3 Solar Cells Enabled by CsI-Doping Strategy.

Antimony selenosulfide (Sb2(S,Se)3) is an emerging quasi-1D photovoltaic semiconductor with exceptional photoelectric properties. The low-symmetry chain structure contains complex defects and makes it difficult to improve electrical properties via doping method. This article reports a doping strategy to enhance the efficiency of Sb2(S,Se)3 solar cells by using alkali halide (CsI) as the hydrothermal reaction precursor. It is found that the Cs and I ions are effectively doped and atomically coordinate with Sb ions and S/Se ions. The CsI-doping Sb2(S,Se)3 absorbers exhibit enhanced grain morphologies and reduced trap densities. The consequential CsI-doping Sb2(S,Se)3 based solar cells demonstrate favorable band alignment, suppressed carrier recombination, and improved device performance. An efficiency as high as 10.05% under standard AM1.5 illumination irradiance is achieved. This precursor-based alkali halide doping strategy provides a useful guidance for high-efficiency antimony selenosulfide solar cells.

2D-HPLC-MS Technology Combined with Molecular Network for the Identification of Components in Tibetan medicine Aconitum pendulum.

In this study, a comprehensive approach was employed, utilizing 2D-HPLC-MS technology in conjunction with the molecular network to unravel the intricate chemical composition of the Tibetan medicinal plant APB. Through the implementation of 2D-HPLC, enhanced separation of complex mixtures was achieved, enabling the isolation of individual compounds for subsequent analysis. The molecular network approach further aided in elucidating structural relationships among these compounds, contributing to the determination of potential bioactive molecules. This integrated strategy efficiently identified a wide array of chemical components present within the plant. The findings revealed a diverse spectrum of chemical constituents within APB, including alkaloids, among others. This research not only advances understanding of the phytochemical profile of this traditional Tibetan medicine but also provides valuable insights into its potential therapeutic properties. The integration of 2D-HPLC-MS and molecular network proves to be a powerful tool for systematically exploring and identifying complex chemical compositions in herbal medicines, paving the way for further research and development in the field of natural product discovery.

Sex-specific associations of maternal and childhood urinary arsenic levels with emotional problems among 6-year-age children: Evidence from a longitudinal cohort study in China.

BACKGROUND: Arsenic exposure has been linked to neurobehavior development disorders among children in cross-sectional studies, but there is little information on the effects of prenatal and childhood arsenic exposure on childhood behavior problem, especially emotional problems. OBJECTIVE: To explore the relationship between prenatal and childhood arsenic exposure and behavior problems among six-year-old children. METHODS: 389 mother-child pairs from a longitudinal birth cohort were enrolled in the study. The concentrations of arsenic in maternal and 6-year-old children's urine were measured using inductively coupled plasma mass spectrometry (ICP-MS). Neurobehavioral development in 6-year-old children was assessed by Child Behavior Checklist (CBCL). Generalized linear regression models were used to relate arsenic exposure to the score of different domains in CBCL. RESULTS: The median concentrations of maternal and 6-year-old children's urinary arsenic were 22.22 and 33.86 µg/L, respectively. After adjusting for potential covariates, natural logarithm transformed concurrent urinary arsenic levels were significantly associated with scores of anxious and depressed problems in 6-year-old girls (ß = 0.71, 95% CI: 0.12-1.31, p = 0.018). Furthermore, in terms of the trajectory of arsenic exposure, compared with the "consistently low" group, the "low to high" group (ß = 2.73, 95% CI: -3.99 to 9.45, p = 0.425) had a greater effect on total score of CBCL than "high to low" group (ß = -0.93, 95% CI: -7.22 to 5.36, p = 0.771) in girls, although insignificant. CONCLUSIONS: Our results suggested that concurrent arsenic exposure might have an adverse effect of emotional status in girls. Further studies are needed to verify the findings and explore the mechanisms of the sex-specific association.

The Progressive Utilization of Ponkan Peel Residue for Regulating Human Gut Microbiota through Sequential Extraction and Modification of Its Dietary Fibers.

As a by-product of citrus processing, ponkan (Citrus reticulata Blanco, cv. Ponkan) peel residue is a source of high quality dietary fiber (DF). To make a full utilization of this resource and give a better understanding on the probiotic function of its DF, soluble dietary fiber (SDF) and insoluble dietary fiber (IDF) were extracted from ponkan peel residue (after flavonoids were extracted) using an alkaline method, followed by modifications using a composite physical-enzymatic treatment. The in vitro fermentation properties of the modified SDF and IDF (namely, MSDF and MIDF) and their effects on short-chain fatty acids (SCFA) production and changes in the composition of human gut microbiota were investigated. Results showed that MSDF and MIDF both significantly lowered the pH value and enhanced total SCFA content in the broths after fermented for 24 h by fecal inocula (p < 0.05) with better effects found in MSDF. Both MSDF and MIDF significantly reduced the diversity, with more in the latter than the former, and influenced the composition of human gut microbiota, especially increasing the relative abundance of Bacteroidetes and decreasing the ratio of Firmicutes to Bacteroidetes (F/B) value. The more influential microbiota by MSDF were g-Collinsella, p-Actinobacteria and g-Dialister, while those by MIDF were f-Veillonellaceae, c-Negativicutes and f-Prevotellacese. These results suggested that the modified ponkan peel residue DF can be utilized by specific bacteria in the human gut as a good source of fermentable fiber, providing a basis for the exploitation of the citrus by-product.

ELP2-NLRP3-GSDMD/GSDME-mediated pyroptosis is induced by TNF-α in MC3T3-E1 cells during osteogenic differentiation.

Tumour necrosis factor-α (TNF-α) is a cytokine involved in systemic inflammation. TNF-α slows down osteogenic differentiation, which may contribute to poor bone development in the inflammatory microenvironment. TNF-α inhibits osteogenic differentiation by activating the JAK-STAT3 pathway, of which Signal transducer and activator of transcription 3 (STAT3)-interacting protein 1 (StIP1, also known as elongator complex protein 2, ELP2) is a key protein in the JAK-STAT3 pathway. We investigated whether and how ELP2 activation mediates the TNF-α-induced pyroptosis during osteoblastic differentiation. Using in vitro cell cultures of preosteoblastic MC3T3-E1 cells, we found that TNF-α exposure causes cell pyroptosis in an inflammatory microenvironment during osteoblastic differentiation. Bioinformatics, protein docking model and co-immunoprecipitation analysis revealed an association between ELP2, STAT3 and NLRP3. Forced ELP2 expression promoted MC3T3-E1 cells pyroptosis, with an increase in the expression of STAT3, NLRP3 inflammasome, GSDMD/GSDME, osteoblast marker genes, and the activity of alkaline phosphatase. In contrast, ELP2 silencing ameliorated MC3T3-E1 cells pyroptosis, and osteogenic differentiation, especially after TNF-α stimulation. The TNF-α-induced cells pyroptosis during osteoblastic differentiation was therefore mediated by ELP2. These results suggest that ELP2 is upregulated at the pyroptosis of MC3T3-E1 cells and inhibits osteogenic differentiation in response to TNF-α through NLRP3-GSDMD/GSDME activation.

Pd-catalyzed intermolecular consecutive double Heck reaction "on water" under air: facile synthesis of substituted indenes.

An efficient and environmentally benign method for the preparation of substituted indene derivatives has been developed by using water as the sole solvent. This reaction proceeded under air, tolerated a wide range of functional-groups and was easily scaled up. Bioactive natural products like indriline were synthesized via the developed protocol. Preliminary results demonstrate that the enantioselective variant can also be achieved.

Alleviative effects of natural plant polysaccharides against DSS-induced ulcerative colitis via inhibiting inflammation and modulating gut microbiota.

Ulcerative colitis (UC) treatment usually involves either drug therapy or surgery. Natural food polysaccharides have showed great potential for preventing UC. In this study, the therapeutic effects of Cyclocarya paliurus (Batal.) Iljinskaja polysaccharide (CP) and Chinese yam polysaccharide (CYP) on dextran sodium sulfate (DSS)-induced mice UC model and their underlying mechanisms were explored. The results suggested that CP and CYP could improve colitis symptoms in DSS-induced mice, enhance the production of IL-10, inhibit cytokines (IL-1ß, TNF-α) and reduce MPO activity. Furthermore, they maintained the integrity of intestine by improving the expression of mucin MUC-2, ZO-1 and occludin, which in turn reduced the contents of lipopolysaccharide binding protein (LBP) and endotoxin (ET) in serum and oxidative stress in liver. Finally, they modulated the composition and metabolism of gut microbiota. Notably, Alistipes and Bacteroides were the specific genera in CP and CYP groups, respectively. These findings indicated that polysaccharides might alleviate the development of colitis and inform other relevant studies.

Object Detection for UAV Aerial Scenarios Based on Vectorized IOU.

Object detection in unmanned aerial vehicle (UAV) images is an extremely challenging task and involves problems such as multi-scale objects, a high proportion of small objects, and high overlap between objects. To address these issues, first, we design a Vectorized Intersection Over Union (VIOU) loss based on YOLOv5s. This loss uses the width and height of the bounding box as a vector to construct a cosine function that corresponds to the size of the box and the aspect ratio and directly compares the center point value of the box to improve the accuracy of the bounding box regression. Second, we propose a Progressive Feature Fusion Network (PFFN) that addresses the issue of insufficient semantic extraction of shallow features by Panet. This allows each node of the network to fuse semantic information from deep layers with features from the current layer, thus significantly improving the detection ability of small objects in multi-scale scenes. Finally, we propose an Asymmetric Decoupled (AD) head, which separates the classification network from the regression network and improves the classification and regression capabilities of the network. Our proposed method results in significant improvements on two benchmark datasets compared to YOLOv5s. On the VisDrone 2019 dataset, the performance increased by 9.7% from 34.9% to 44.6%, and on the DOTA dataset, the performance increased by 2.1%.

Microencapsulation with Different Starch-Based Polymers for Improving Oxidative Stability of Cold-Pressed Hickory (Carya cathayensis Sarg.) Oil.

Hickory (Carya cathayensis Sarg.) oil is a nutrient-dense edible woody oil, with its unsaturated fatty acids accounting for more than 90% of total ones, and liable to oxidation spoilage. To efficiently improve its stability and expand its application fields, the microencapsulation of cold-pressed hickory oil (CHO) by the molecular embedding method and freeze-drying technique was performed using malt dextrin (MD), hydroxylpropyl-ß-cyclodextrin (HP-ß-CD), ß-cyclodextrin (ß-CD), or porous starch (PS) as a wall material. Two wall materials and/or their CHO microcapsulates (CHOM) with higher encapsulation efficiencies (EE) were selected to carry out physical and chemical characterizations using laser particle size diffractometer, scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, derivative thermogravimetry, and oxidative stability tests. Results indicated ß-CDCHOM and PSCHOM had significantly higher EE values (80.40% and 75.52%) than MDCHOM and HP-ß-CDCHOM (39.36% and 48.32%). The particle sizes of the two microcapsules selected were both widely distributed with their spans being more than 1 µm and a certain degree of polydispersity. Microstructural and chemical characterizations indicated that ß-CDCHOM had comparatively stable structure and good thermal stability compared with PSCHOM. Storage performances under light, oxygen, and temperature showed that ß-CDCHOM was superior to PSCHOM, especially in terms of thermal and oxidative stability. This study demonstrates that ß-CD embedding can be applied to improve the oxidative stability of vegetable oils such as hickory oil and act as a means of preparing functional supplementary material.

A comprehensive review of Shengdeng in Tibetan medicine: textual research, herbal and botanical distribution, traditional uses, phytochemistry, and pharmacology.

"Shengdeng", a group of Tibetan medicines with diverse biological origins, has long been utilized in Tibet for the treatment of rheumatoid arthritis. It showcases remarkable efficacy in alleviating rheumatism, reducing swelling, and relieving pain. This study aimed to clarify the plant species used as "Shengdeng" and summarize their botanical distribution, traditional uses, phytochemistry, and pharmacology to promote its utilization and development. "Shengdeng" is derived from a remarkable collection of 14 plant species belonging to six distinct families. Extensive phytochemical investigations have led to the identification of 355 chemical constituents within "Shengdeng". Pharmacological studies conducted on "Shengdeng" have revealed a wide range of beneficial properties, including antioxidant, anticancer, antimicrobial, antiviral, antiparasitic, anti-inflammatory, and anti-arthritic activities. Notably, flavonoids and triterpenoids emerge as the predominant groups among these constituents, contributing to the therapeutic potential and diverse applications of "Shengdeng". The present review provides a concise summary of the recent advancements in textual research concerning the herbal and botanical distribution, traditional uses, phytochemistry, and pharmacological activities of "Shengdeng". It is crucial to note that future research on "Shengdeng" should prioritize the analysis of its active ingredients and the establishment of rigorous quality standards. These aspects are essential for ensuring consistency, efficacy, and safety in its clinical application.

miRNA-382-5p Carried by Extracellular Vesicles in Osteoarthritis Reduces Cell Viability and Proliferation, and Promotes Cell Apoptosis by Targeting PTEN.

The objective of the study was to identify extracellular vesicle (EV) microRNAs (miRNAs) that play important roles in knee osteoarthritis (OA). Models of knee OA were surgically induced in nine male Sprague-Dawley rats. Tissue samples were collected at 0 weeks (Control), 6 weeks (6 weeks), and 12 weeks (12 weeks). The EVs were isolated and analyzed for size. Various biomarkers, including recombinant tetraspanin 30 cluster of differentiation (CD)63 and CD9 were detected. An Agilent array was used to screen for differentially expressed (DE) miRNAs. The levels of DE miRNAs and their target mRNAs were evaluated by quantitative reverse transcription-polymerase chain reaction and western blotting. The viability, proliferation, and apoptosis of lipopolysaccharide (LPS)-induced human synovial cells (HSCs) were examined by using Cell Counting Kit-8, EdU (5-ethynyl-2'-deoxyuridine), and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) assays, respectively. The OA model rats had significantly increased levels of inflammatory activity, damaged cells, and rough articular cartilage when compared with rats in the control group. The EVs from the model rats appeared as round vesicle-like structures with a mean diameter of ∼145 nm. Five miRNAs that showed gradual increases in the model rats were selected for further analysis; those miRNAs included miR-127-3p, miR-132-3p, miR-141-3p, miR-345-5p, and miR-382-5p. miR-382-5p was found to reduce the viability and proliferation and promote the apoptosis of LPS-induced HSCs. Moreover, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was negatively regulated by miR-382-5p. Our findings revealed that EVs produced by the OA rats contained miR-382-5p, which might reduce cell viability and proliferation, and promote cell apoptosis by targeting PTEN.

Transverse Tibial Bone Transport Enhances Distraction Osteogenesis and Vascularization in the Treatment of Diabetic Foot.

OBJECTIVE: To investigate the effect of transverse tibial bone transport on the treatment of Wagner Stage 4 diabetic foot. METHODS: From January 2017 to October 2019, a total of 19 patients with Wagner Stage 4 diabetic foot ulcers were recruited. All patients were treated with transverse tibial bone transport. A detailed follow-up was carried out at 1 week, 1 month, 3 months, 6 months, and 1 year after surgery. The wound healing rate and the limb salvage rate at 1 year after the surgery were evaluated. Preoperative and 3-month postoperative digital subtraction angiography (DSA) were obtained. The level of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) before surgery and on 1st, 4th, 11th, 18th, 28th , and 35th days after surgery were measured. Operation time, intraoperative blood loss, postoperative complications, visual analog scale (VAS) pain score, skin temperature, Semmes-weinstein monofilament (SWM), and ankle brachial index (ABI) were also assessed. RESULTS: The wound healing rate and the limb salvage rate were both 94.74% in the patients at 1 year after the surgery. DSA showed the thickening of the calf and foot arteries, clear visualization, and a rich vascular network. The levels of VEGF, bFGF, and PDGF on the 11th, 18th, 28th , and 35th days after surgery were significantly higher than those before surgery (p < 0.05). The EGF level on the 18th, 28th, and 35th days after surgery was significantly higher than that before surgery (p < 0.05). Superficial wound complications occurred in one patient during the hospitalization. There was no movement area infection, skin flap necrosis, tibial fracture, loosening of the external fixator, or rupture in study. CONCLUSION: Transverse tibial bone transport can improve the blood circulation of the affected limbs, promote the healing of diabetic foot wounds, and reduce the amputation rate of the affected limbs. Transverse tibial bone transport can promote the healing of Wagner Stage 4 diabetic foot.

Purple red rice anthocyanins alleviate intestinal damage in cyclophosphamide-induced mice associated with modulation of intestinal barrier function and gut microbiota.

The regulatory effects of purple red rice bran anthocyanins (PRBA) on intestinal barrier function and gut microbiota in mice were investigated. Results showed that PRBA had an ameliorative effect on intestinal barrier damage, including restoration of villus length, improvement in the number of cupped cells and promotion of sIgA secretion. PRBA stimulated the production of cytokines, reduced the levels of endotoxin (ET) and lipopolysaccharide binding protein (LBP) in serum, as well as upregulated the expression of tight junction proteins (TJs) and NF-κB pathway proteins. Furthermore, PRBA not only promoted the production of short-chain fatty acids (SCFAs), but also regulated the intestinal microbiota by increasing beneficial bacteria (Lachnospiraceae, Bacteroidaceae, Ruminococcaceae) and reducing pathogenic bacteria (Shigella) to maintained intestinal homeostasis. Above results indicated that PRBA could ameliorate cyclophosphamide-induced impairment of intestinal barrier function and dysregulation of the gut microbiota, which provides a new idea for broadening the exploitation of PRBA.

Mesona chinensis Benth Polysaccharides Alleviate DSS-Induced Ulcerative Colitis via Inhibiting of TLR4/MAPK/NF-κB Signaling Pathways and Modulating Intestinal Microbiota.

SCOPE: Ulcerative colitis (UC) is a severe disease of the intestinal tract. To investigate the role of TLR4/Mitogen-activated protein kinase (MAPK)/Nuclear factor kappa-B(NF-κB) pathways and intestinal flora in UC, and the protective mechanisms of Mesona chinensis Benth polysaccharides (MBP), potential therapeutic agents due to their diabetes-relieving, cancer-suppressing, and immunomodulatory properties. METHODS AND RESULTS: A dextran sulfate sodium (DSS)-induced mouse colitis model is used for experiments; the histopathology, immunohistochemistry, and Western blotting's results suggest that MBP can alleviate the colitis symptoms, inhibits the overproduction of TNF-α, IL-1ß, promote IL-10, reduces myeloperoxidase activity, and alleviates the inflammatory response probably by inhibiting the activation of TLR4/MAPK/NF-κB pathways. Furthermore, MBP improvs the ratio of Bcl-2/BAX, maintains the intestinal integrity by promoting the levels of zonulin occludin-1 (ZO-1), occluding and mucin mucin-2 (MUC-2), reduces the levels of endotoxin (ET), lipopolysaccharide binding protein (LBP) in serum, and oxidative stress in liver. Moreover, using 16S rRNA Gene Sequencing analysis, MBP regulates gut microbiota by decreasing the abundances of Helicobacter and Prevotella and increasing the abundances of Lactobacillus and Coprococcus, reverses microbiota dysbiosis caused by DSS. CONCLUSION: These findings confirm the anti-inflammatory effects of MBP, restoration of the intestinal barrier and intestinal flora, and have therapeutic potential to attenuate the development of UC.

The silencing of miR-199a-5p protects the articular cartilage through MAPK4 in osteoarthritis.

Background: Osteoarthritis (OA) is the most common joint disorder, and places a heavy burden on individuals and society. As conventional therapies, such as surgery, rarely cure the disorder, targeted therapies represent a promising alternative. This research sought to explore the potential effect of miR-199a-5p on the development of OA. Methods: Based on the OA rat model, the serum was collected at 6 and 12 weeks, and microRNA (miRNA) sequencing was performed. A bioinformatics analysis was conducted to examine the differentially expressed micro ribonucleic acids, and qRT-PCR (real-time quantitative PCR) was conducted to determine their expression in the joint tissues of rats with OA. Rats articular chondrocytes were collected and treated with a miR-199a-5p antagomir or agomir. Afterwards, cell viability, autophagy was determinated. Dual luciferase was used to verify that miR-199a-5p targets the regulation of mitogen-stimulated protein kinase 4 (MAPK4). Subsequently, in chondrocytes, MAPK was knockdown to rescue the effect of miR-199a-5p inhibition, and cell viability and autophagy were examined. Finally, the OA model was treated with miR-199a-5p antagomir to detect joint pathology, cartilage tissue and inflammatory factor and autophagy was measured. Results: MiR-199a-5p was greatly upregulated in OA, and miRNA was found to be differentially expressed in OA tissues. MAPK4 was identified to be a target gene of miR-199-5p. Inhibiting miR-199a-5p not only decreased the survival of chondrocytes and induced apoptosis, but also relieved inflammation and decreased the content of pro-inflammatory cytokines. Further, the silencing of miR-199a-5p protected the articular cartilage and improved gait abnormalities, but this effect was abrogated by the silencing of MAPK4. Conclusions: The silencing of miR-199a-5p appears to improve gait abnormalities, promote the survival of chondrocytes, and improve the condition of OA. Our findings may lead to the development of miR-199a-5p-based targeted therapy for OA.