The truncated IFITM3 facilitates the humoral immune response in inactivated influenza vaccine-vaccinated mice via interaction with CD81.

A single-nucleotide polymorphism (SNP) rs12252-C of interferon-induced transmembrane protein 3 (IFITM3), resulting in a truncated IFITM3 protein lacking 21 N-terminus amino acids, is associated with severe influenza infection in the Chinese population. However, the effect of IFITM3 rs12252-C on influenza vaccination and the underlying mechanism is poorly understood. Here, we constructed a mouse model with a deletion of 21 amino acids at the N-terminus (NΔ21) of IFITM3 and then compared the antibody response between Quadrivalent influenza vaccine (QIV) immunized wild-type (WT) mice and NΔ21 mice. Significantly higher levels of haemagglutination inhibition (HI) titre, neutralizing antibodies (NAb), and immunoglobulin G (IgG) to H1N1, H3N2, B/Victory, and B/Yamagata viruses were observed in NΔ21 mice compared to WT mice. Correspondingly, the numbers of splenic germinal centre (GC) B cells, plasma cells, memory B cells, QIV-specific IgG+ antibody-secreting cells (ASC), and T follicular helper cells (TFH) in NΔ21 mice were higher compared with WT mice. Moreover, the 21-amino-acid deletion caused IFITM3 translocation from the endocytosis compartment to the periphery of cells, which also prevented the degradation of a co-stimulatory molecule of B cell receptor (BCR) CD81 on the cell surface. More importantly, a more interaction was observed between NΔ21 protein and CD81 compared to the interaction between IFITM3 and CD81. Overall, our study revealed a potential mechanism of NΔ21 protein enhancing humoral immune response by relocation to prevent the degradation of CD81, providing insight into SNP affecting influenza vaccination.

Comparison of pharmacological activity and safety of different stereochemical configurations of borneol: L-borneol, D-borneol, and synthetic borneol.

BACKGROUND: Chiral drugs generally exhibit differences in activity because they bind differently to their target receptor. The Chinese medicine borneol ('Bing Pian' in Chinese) is a bicyclic monoterpenoid with a wide range of biological activities. Three kinds of Chinese medicines comprising borneol are used clinically, namely, L-Borneolum ('Ai Pian' in Chinese), Borneolum ('Tian Ran Bing Pian' in Chinese), and synthetic borneol ('He Cheng Bing Pian' in Chinese). The three kinds of borneol have different stereochemical configurations, but their clinical uses are nearly identical, and their prices vary widely. However, there is no clear rational basis for the selection of these kinds of borneol in clinical applications. PURPOSE: The purpose of this study was to clarify differences in the biological activity, safety, and structure-activity relationship of the three kinds of borneol. METHODS: 'borneol', 'Bing Pian', 'Ai Pian', 'Tian Ran Bing Pian', and 'He Cheng Bing Pian' were selected as keywords to search for and extract relevant literature in the CNKI, PubMed, and Google Scholar databases up to November 2022. RESULTS: L-borneol has better potential in cerebrovascular diseases. The three kinds of borneol have stronger penetration-promoting effects on hydrophilic drugs. L-borneol and isoborneol promote intestinal mucosal absorption of drugs via bidirectional regulation of P-glycoprotein. D-borneol exhibits better antitumour sensitizing effects than L-borneol. L-borneol exhibits better inhibition of bacterial adhesion because of its C2 chiral centre. Synthetic borneol is less safe. CONCLUSION: L-borneol has excellent potential in many aspects, has various sources, and can effectively replace expensive D-borneol in some applications.

l-borneol promotes neurovascular unit protection in the subacute phase of transient middle cerebral artery occlusion rats: p38-MAPK pathway activation, anti-inflammatory, and anti-apoptotic effect.

Our previous study showed l-borneol reduced cerebral infarction in the acute stage after cerebral ischemia, but there is little about the study of subacute phase. We herein investigated the cerebral protective effects of l-borneol on neurovascular units (NVU) in the subacute phase after transient middle cerebral artery occlusion (t-MCAO). The t-MCAO model was prepared by the line embolus method. Zea Longa, mNss, HE, and TTC staining were used to evaluate the effect of l-borneol. We evaluated the mechanisms of l-borneol on inflammation, p38 MAPK pathway, and apoptosis, etc. through various technologies. l-borneol 0.2, 0.1, 0.05 g·kg-1 could significantly reduce cerebral infarction rate, alleviate the pathological injury, and inhibit inflammation reaction. l-borneol could also significantly increase brain blood supply, Nissl bodies, and the expression of GFAP. Additionally, l-borneol activated the p38 MAPK signaling pathway, inhibited cell apoptosis, and maintained BBB integrity. l-borneol had a neuroprotective effect, which was related to activating the p38 MAPK signaling pathway, inhibiting inflammatory response and apoptosis, and improving cerebral blood supply to protect BBB and stabilize and remodel NVU. The study will provide a reference for the use of l-borneol in the treatment of ischemic stroke in the subacute phase.

Identification of Andrographolide as a novel FABP4 inhibitor for osteoarthritis treatment.

BACKGROUND AND PURPOSE: Fatty acid binding protein 4 (FABP4) has been identified as a contributor to cartilage degradation in osteoarthritis (OA) patients, and inhibiting FABP4 using small molecules has emerged as a promising approach for developing OA drugs. Our previous research showed that Andrographis paniculata, a medicinal plant, strongly inhibits FABP4 activity. This led us to hypothesize that Andrographis paniculata ingredients might have protective effects on OA cartilage through FABP4 inhibition. METHODS: We analyzed scRNA-seq data from joint tissue of OA patients (GSE152805; GSE145286) using Scanpy 1.9.1 and Single Cell Portal. We conducted docking analysis of FABP4 inhibitors using Autodock Vina v.1.0.2. We evaluated the anti-FABP4 activity using a fluorescence displacement assay and measured the fatty acid oxidation (FAO) activity using the FAOBlue assay. We used H2DCF-DA to measure reactive oxygen species (ROS) levels. We studied signaling pathways using bulk RNA sequencing and western blot analysis in human C28/I2 chondrocytes. We evaluated anti-OA activity in monosodium iodoacetate (MIA)-induced rats. RESULTS: We identified Andrographolide (AP) as a novel FABP4 inhibitor. Bulk RNA-sequencing analysis revealed that FABP4 upregulated FAO and ROS in chondrocytes, which was inhibited by AP. ROS generation activated the NF-κB pathway, leading to overexpression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4), which is a responsible factor for cartilage degradation in OA patients. AP inhibited FABP4, thereby reducing the overexpression of ADAMTS4 by inhibiting the NF-κB pathway. In MIA rats, AP treatment reduced the overexpression of ADAMTS4, repaired cartilage and subchondral bone, and promoted cartilage regeneration. CONCLUSION: Our results indicate that the inhibition of FABP4 activity by AP explains the anti-OA properties of Andrographis paniculata by protecting against cartilage degradation in OA patients. Additionally, our findings suggest that AP may be a promising therapeutic agent for OA treatment due to its ability to alleviate cartilage damage and bone erosion.

[Protective effects of three kinds of borneol on different brain regions in acute cerebral ischemia/reperfusion model rats].

This study compared the ameliorating effects of L-borneol, natural borneol, and synthetic borneol on the injury of different brain regions in the rat model of acute phase of cerebral ischemia/reperfusion(I/R) for the first time, which provides a reference for guiding the rational application of borneol in the early treatment of ischemic stroke and has important academic and application values. Healthy specific pathogen-free(SPF)-grade SD male rats were randomly assigned into 13 groups: a sham-operation group, a model group, a Tween model group, a positive drug(nimodipine) group, and high-, medium-, and low-dose(0.2, 0.1, and 0.05 g·kg~(-1), respectively) groups of L-borneol, natural borneol, and synthetic borneol according to body weight. After 3 days of pre-administration, the rat model of I/R was established by suture-occluded method and confirmed by laser speckle imaging. The corresponding agents in different groups were then administered for 1 day. The body temperature was monitored regularly before pre-administration, days 1, 2, and 3 of pre-administration, 2 h after model awakening, and 1 d after model establishment. Neurological function was evaluated based on Zea-Longa score and modified neurological severity score(mNSS) 2 h and next day after awakening. The rats were anesthetized 30 min after the last administration, and blood was collected from the abdominal aorta. Enzyme-linked immunoassay assay(ELISA) was employed to determine the serum levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), IL-4, and transforming growth factor-beta1(TGF-ß1). The brain tissues were stained with triphenyltetrazolium chloride(TTC) for the calculation of cerebral infarction rate, and hematoxylin-eosin(HE) staining was used for observing and semi-quantitatively evaluating the pathological damage in different brain regions. Immunohistochemistry was employed to detect the expression of ionized calcium binding adapter molecule 1(IBA1) in microglia. q-PCR was carried out to determine the mRNA levels of iNOS and arginase 1(Arg1), markers of polarization phenotype M1 and M2 in microglia. Compared with the sham-operation group, the model group and the Tween model group showed significantly elevated body temperature, Zea-Longa score, mNSS, and cerebral infarction rate, severely damaged cortex, hippocampus, and striatum, increased serum levels of IL-6 and TNF-α, and decreased serum levels of IL-4 and TGF-ß1. The three borneol products had a tendency to reduce the body temperature of rats 1 day after modeling. Synthetic borneol at the doses of 0.2 and 0.05 g·kg~(-1), as well as L-borneol of 0.1 g·kg~(-1), significantly reduced Zea-Longa score and mNSS. The three borneol products at the dose of 0.2 g·kg~(-1) significantly reduced the cerebral infarction rate. L-borneol at the doses of 0.2 and 0.1 g·kg~(-1) and natural borneol at the dose of 0.1 g·kg~(-1) significantly reduced the pathological damage of the cortex. L-borneol and natural borneol at the dose of 0.1 g·kg~(-1) attenuated the pathological damage of hippocampus, and 0.2 g·kg~(-1) L-borneol attenuated the damage of striatum. The 0.2 g·kg~(-1) L-borneol and the three doses of natural borneol and synthetic borneol significantly reduced the serum level of TNF-α, and the 0.1 g·kg~(-1) synthetic borneol reduced the level of IL-6. L-borneol and synthetic borneol at the dose of 0.2 g·kg~(-1) significantly inhibited the activation of cortical microglia, and 0.2 g·kg~(-1) L-borneol up-regulated the expression of Arg1 and down-regulated the expression level of iNOS. In conclusion, the three borneol products may alleviate inflammation to ameliorate the pathological damage of brain regions of rats in the acute phase of I/R by inhibiting the activation of microglia and promoting the polarization of microglia from M1 type to M2 type. The protective effect on brain followed a trend of L-borneol > synthetic borneol > natural borneol. We suggest L-borneol the first choice for the treatment of I/R in the acute phase.

Shang-Ke-Huang-Shui and coptisine alleviate osteoarthritis in the knee of monosodium iodoacetate-induced rats through inhibiting CXCR4 signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Shang-Ke-Huang-Shui (SKHS) is a classic traditional Chinese medicine formula originally from the southern China city of Foshan. It has been widely used in the treatment of osteoarthritis (OA) but underlying molecular mechanisms remain unclear. AIM OF STUDY: Recently, activation of C-X-C chemokine receptor type 4 (CXCR4) signaling has been reported to induce cartilage degradation in OA patients; therefore, inhibition of CXCR4 signaling has becoming a promising approach for OA treatment. The aim of this study was to validate the cartilage protective effect of SKHS and test whether the anti-OA effects of SKHS depend on its inhibition on CXCR4 signaling. Additionally, CXCR4 antagonist in SKHS should be identified and its anti-OA activity should also be tested in vitro and in vivo. METHODS: The anti-OA effects of SKHS and the newly identified CXCR4 antagonist was evaluated by monosodium iodoacetate (MIA)-induced rats. The articular cartilage surface was examined by hematoxylin and eosin (H&E) staining and Safranin O-Fast Green (S-F) staining whereas the subchondral bone was examined by micro-CT. CXCR4 antagonist screenings were conducted by molecular docking and calcium response assay. The CXCR4 antagonist was characterized by UPLC/MS/MS. The bulk RNA-Seq was conducted to identify CXCR4-mediated signaling pathway. The expression of ADAMTS4,5 was tested by qPCR and Western blot. RESULTS: SKHS protected rats from MIA-induced cartilage degradation and subchondral bone damage. SKHS also inhibited CXCL12-indcued ADAMTS4,5 overexpression in chondrocytes through inhibiting Akt pathway. Coptisine has been identified as the most potent CXCR4 antagonist in SKHS. Coptisine reduced CXCL12-induced ADAMTS4,5 overexpression in chondrocytes. Furthermore, in MIA-induced OA model, the repaired cartilage and subchondral bone were observed in the coptisine-treated rats. CONCLUSION: We first report here that the traditional Chinese medicine formula SKHS and its predominate phytochemical coptisine significantly alleviated cartilage degradation as well as subchondral bone damage through inhibiting CXCR4-mediated ADAMTS4,5 overexpression. Together, our work has provided an important insight of the molecular mechanism of SKHS and coptisine for their treatment of OA.

Aroma formation and transformation during sealed yellowing process of Pingyang yellow tea.

Yellow tea, a unique type of tea in China which is characterized with yellow color, has gained increasing popularity due to its pleasant taste. However, transformation of aroma compounds during sealed yellowing has been poorly understood. Results of sensory evaluation exhibited that yellowing time was the key factor for flavor and fragrance formation. A total of 52 volatile components during sealed yellowing process of Pingyang yellow soup were further collected and analyzed. The results demonstrated that the sealed yellowing process significantly increased the ratio of alcohol and aldehyde compounds in the aroma volatiles of yellow tea, which were primarily composed of geraniol, linalool, phenylacetaldehyde, linalool oxide and cis-3-hexenol, and their proportion increased with the prolongation of sealed yellowing. Mechanistic speculation revealed that the sealed yellowing process promoted release of alcoholic aroma compounds from their glycoside precursors and enhanced Strecker and oxidative degradation. This study revealed the transformation mechanism of aroma profile during the sealed yellowing process, which would facilitate processing of yellow tea.

Enzyme and Reactive Oxygen Species-Responsive Dual-Drug Delivery Nanocomplex for Tumor Chemo-Photodynamic Therapy.

Introduction: Combination therapy is a promising approach to promote the efficacy and reduce the systemic toxicity of cancer therapy. Herein, we examined the potency of a combined chemo-phototherapy approach by constructing a hyaluronidase- and reactive oxygen species-responsive hyaluronic acid nanoparticle carrying a chemotherapy drug and a photosensitizer in a tumor-bearing mouse model. We hypothesized that following decomposition, the drugs inside the nanocomplex will be released in the tumors to provide effective tumor treatment. We aimed to design a smart drug delivery system that can improve traditional chemotherapy drug delivery and enhance the therapeutic efficacy in combination with photodynamic therapy. Methods: Hydrophilic hyaluronic acid (HA) was covalently modified with a hydrophobic 5ß-cholanic acid (CA) via an ROS-cleavable thioketal (tk) linker for a targeted co-deliver of 10-Hydroxy camptothecin (HCPT) and Chlorin e6 (Ce6) into tumors to improve the efficiency of combined chemo-photodynamic therapy. Results: The obtained HA-tk-CA nanoparticle carrying HCPT and Ce6, named HTCC, accumulated in the tumor through the enhanced permeable response (EPR) effect and HA-mediated CD44 targeting after intravenous administration. Upon laser irradiation and hyaluronidase degradation, HTCC was disrupted to release HCPT and Ce6 into the tumors. Compared to the monotherapy approach, HTCC demonstrated enhanced tumor growth inhibition and minimized systemic toxicity in a tumor-bearing mouse model. Conclusion: Our results suggested that controlled dual-drug release not only improved tumor drug delivery efficacy, but also reduced systemic side effects. In addition to HCPT and Ce6 delivery, the HA-tk-CA nanocomplex can be used to deliver other drugs in synergistic cancer therapy. Since most current combined therapy uses free drugs with distinct spatiotemporal distributions, the simultaneous co-delivery of dual drugs with a remote on-demand drug delivery nanosystem provides an alternative strategy for drug delivery design.

l-Borneol and d-Borneol promote transdifferentiation of astrocytes into neurons in rats by regulating Wnt/Notch pathway to exert neuroprotective effect during recovery from cerebral ischaemia.

BACKGROUND: The Chinese medicines Borneolum and l-Borneolum have neuroprotective effects on acute cerebral ischaemia-reperfusion (IR) in rats. Research on their effects during recovery from cerebral IR is lacking. Cerebral ischaemia can activate astrocytes for conversion into neurons. Neurogenesis cannot be achieved without nutritional support from an improved brain microenvironment through the blood circulation. PURPOSE: The purpose of this study was to determine whether Borneolum and l-Borneolum can promote transdifferentiation of astrocytes into neurons by regulating the Wnt/Notch pathway to exert neuroprotective effects during recovery from cerebral ischaemia. STUDY DESIGN AND METHODS: A suture crossing the external carotid artery to occlude the middle cerebral artery was used to prepare a model of cerebral IR (Longa et al., 1989). The Longa neurological function score, modified neurological severity score, tape removal test and grid misstep experiment were used to evaluate motor nerve function. Triphenyltetrazolium chloride was used to determine the extent of cerebral infarction. Left/right hemisphere contrast was used to measure brain atrophy. Astrocytes labelled with adeno-associated virus were used to track their fate after transdifferentiation. Laser speckle contrast imaging was used to observe the effects of l-Borneolum and Borneolum on cerebral blood flow. Immunofluorescence and western blotting were used to investigate their mechanisms. RESULTS: l-Borneolum and Borneolum significantly improved neurological function and limb movement in rats with cerebral ischaemia during recovery and increased cerebral blood flow. l-Borneolum improved forelimb motor coordination more effectively than Borneolum and promoted transdifferentiation of astrocytes to GABAergic neurons in the striatal region. The expression of Wnt3a and Notch-1 was downregulated. The expression of vascular endothelial growth factor was not significantly changed. Borneolum improved forelimb sensitivity and alleviated cerebral infarction and brain atrophy more effectively than l-Borneolum, which promoted transdifferentiation of astrocytes into neurons and nestin expression and neurogenesis in the striatal zone. The expression of glycogen synthase kinase-3ß and ß-catenin was upregulated. l-Borneolum and Borneolum had no significant neuroprotective effect on the cortex and hippocampus. CONCLUSIONS: l-Borneolum and Borneolum exerted neuroprotective effects on cerebral ischaemia during recovery by promoting neurogenesis and blood circulation in the striatal and subventricular zones. Their mechanisms may be related to the Wnt3a and Notch-1 pathways.

Astragaloside IV as a novel CXCR4 antagonist alleviates osteoarthritis in the knee of monosodium iodoacetate-induced rats.

BACKGROUND AND PURPOSE: C-X-C chemokine receptor type 4 (CXCR4) inhibition protects cartilage in osteoarthritis (OA) animal models. Therefore, CXCR4 has becoming a novel target for OA drug development. Since dietary and herbal supplements have been widely used for joint health, we hypothesized that some supplements exhibit protective effects on OA cartilage through inhibiting CXCR4 signaling. METHODS: The single-cell RNA sequencing data of OA patients (GSE152805) was re-analyzed by Scanpy 1.9.0. The docking screening of CXCR4 antagonists was conducted by Autodock Vina 1.2.0. The CXCR4 antagonistic activity was evaluated by calcium response in THP-1 cells. Signaling pathway study was conducted by bulk RNA sequencing and western blot analysis in human C28/I2 chondrocytes. The anti-OA activity was evaluated in monosodium iodoacetate (MIA)-induced rats. RESULTS: Astragaloside IV (ASN IV), the predominate phytochemical in Astragalus membranaceus, has been identified as a novel CXCR4 antagonist. ASN IV reduced CXCL12-induced ADAMTS4,5 overexpression in chondrocytes through blocking Akt signaling pathway. Furthermore, ASN IV administration significantly repaired the damaged cartilage and subchondral bone in MIA-induced rats. CONCLUSION: The blockade of CXCR4 signaling by ASN IV could explain anti-OA activities of Astragalus membranaceus by protection of cartilage degradation in OA patients. Since ASN IV as an antiviral has been approved by China National Medical Products Administration for testing in people, repurposing of ASN IV as a joint protective agent might be a promising strategy for OA drug development.

Glycyrrhizin Inhibits SARS-CoV-2 Entry into Cells by Targeting ACE2.

Coronavirus Disease 2019 (COVID-19) is a highly infectious and pathogenic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early in this epidemic, the herbal formulas used in traditional Chinese medicine (TCM) were widely used for the treatment of COVID-19 in China. According to Venn diagram analysis, we found that Glycyrrhizae Radix et Rhizoma is a frequent herb in TCM formulas against COVID-19. The extract of Glycyrrhizae Radix et Rhizoma exhibits an anti-SARS-CoV-2 replication activity in vitro, but its pharmacological mechanism remains unclear. We here demonstrate that glycyrrhizin, the main active ingredient of Glycyrrhizae Radix et Rhizoma, prevents the coronavirus from entering cells by targeting angiotensin-converting enzyme 2 (ACE2). Glycyrrhizin inhibited the binding of the spike protein of the SARS-CoV-2 to ACE2 in our Western blot-based assay. The following bulk RNA-seq analysis showed that glycyrrhizin down-regulated ACE2 expression in vitro which was further confirmed by Western blot and quantitative PCR. Together, we believe that glycyrrhizin inhibits SARS-CoV-2 entry into cells by targeting ACE2.

d-Borneol enhances cisplatin sensitivity via autophagy dependent EMT signaling and NCOA4-mediated ferritinophagy.

BACKGROUND: d-Borneol has been widely used as a drug absorption enhancer, but there are few studies on the anti-resistance ability of d-borneol combined with cisplatin in cisplatin-resistant non-small cell lung cancer cells. Ferroptosis, autophagy and epithelial-mesenchymal transition (EMT) have been reported to be associated with drug resistance. PURPOSE: To investigate the molecular mechanisms and sensitizing effects of d-borneol combined with cisplatin to against drug cisplatin resistance from the perspective of ferroptosis, autophagy and EMT resistance. METHODS: H460/CDDP xenograft tumor model was established to verify the antitumor activity and safety in vivo. RNA sequencing was used to predict target molecules and signaling pathways. Reactive oxygen species (ROS) were used as marker of ferroptosis, and its level was determined by a dichlorodihydrofluorescein diacetate fluorescent probe and flow cytometry. Levels of glutathione (GSH), malondialdehyde (MDA), and antioxidants such as superoxide dismutase (SOD) and thioredoxin (Trx) involved in the balance of oxidative stress were measured by an assay kit or enzyme-linked immunosorbent assay. Western blotting and real-time polymerase chain reaction were used to assess the regulatory mechanism of EMT markers, autophagy, and ferroptosis signaling pathways. RESULTS: d-Borneol in combination with cisplatin reduced tumor volume and weight, enhanced tumor-inhibiting effects, and alleviated cisplatin-induced damage to the liver and kidney in vivo. RNA-sequencing showed that differentially expressed genes were enriched in ferroptosis. d-Borneol in combination with cisplatin promoted ROS accumulation, increased the content of MDA levels, and decreased GSH, SOD, Trx, and heme oxygenase-1 expression to induce oxidative damage. d-Borneol combination with cisplatin induced ferroptosis by promoting nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and regulating intracellular iron ion transport via upregulating PRNP and downregulating PCBP2. In addition, d-borneol combined with cisplatin promoted autophagy by upregulating expression of LC3II/ATG5/Beclin-1 and inhibited the EMT by increasing the expression of epithelial marker E-cadherin and decreasing mesenchymal markers (N-cadherin and vimentin) and transcription factors (Snail and ZEB1). CONCLUSION: For the first time, our study implies that d-borneol enhanced cisplatin sensitivity by inducing ferroptosis, promoting autophagy and inhibiting EMT progression, thereby enhancing antitumor activity. It suggests that d-borneol could be developed as a novel chemosensitizers.

Protective effects of lavender oil on sepsis-induced acute lung injury via regulation of the NF-κB pathway.

CONTEXT: Lavender oil (Lav) from Lavandula angustifolia L. (Lamiacease) exhibits antioxidative and anti-inflammatory properties against various diseases. OBJECTIVE: The study explores the effect of Lav pre-treatment on sepsis-induced acute lung injury (ALI). MATERIALS AND METHODS: Sprague-Dawley rats were assigned into Sham, caecal ligation and puncture (CLP), CLP + Lav (200, 400, and 800 mg/kg) groups. Lav was administered by gavage, once a day, for 7 days. Histological analysis was performed using haematoxylin and eosin staining. Cytokine and nitrite levels were detected by enzyme-linked immunosorbent assay kits and Griess reagent. Gene and protein expression were tested by quantitative real-time polymerase chain reaction and western blot. RESULTS: The levels of tumour necrosis factor-α (BALF: 64%, serum: 59%), interleukin (IL)-1ß (BALF: 63%, serum: 66%) and IL-6 (BALF: 54%, serum: 59%), and nitrite (40%) and inducible nitric oxide synthase (51%), and the level of myeloperoxidase (66%) and malondialdehyde (59%), and cleaved-caspase 3 (84%) and Bax expression (74%) induced by CLP were decreased when given Lav. Additionally, the level of superoxide dismutase (211%) and glutathione (139%), and the expression of Bcl-2 (980%) induced by CLP were increased when given Lav. The increased p-nuclear factor (NF)-κB/NF-κB (72%) and p-inhibitor of κBα (IκBα)/IκBα (77%) induced by CLP could be reversed by Lav. DISCUSSION AND CONCLUSIONS: Lav pre-treatment might protect rats from sepsis-induced ALI via deactivation of the NF-κB pathway. Our research demonstrated the regulatory mechanisms of Lav in sepsis-induced ALI and can provide a theoretical basis for the use of Lav in the treatment of sepsis-induced ALI.

The effects of magnolol supplementation on growth performance, meat quality, oxidative capacity, and intestinal microbiota in broilers.

The aim of the present study was to evaluate the effect of magnolol (MAG) on growth performance, meat quality, oxidative capacity, and intestinal microbiota in the yellow-feather broilers. A total of 360 one-day-old male yellow-feather broiler chicks were allocated into 5 groups of 6 replicates and 12 chickens per replicate, were fed a basal diet supplemented with 0 (Control group, CON), 100, 200, 300, or 400 mg/kg MAG for 51 d. The results showed that dietary supplementation with 200 and 300 mg/kg MAG increased the average daily gain (ADG) but decreased feed to gain ratio (F/G) during the overall periods (P < 0.05). Dietary MAG increased significantly the redness value (a∗) of the breast muscle (P < 0.05), and decreased the water loss rate and shear force of the breast meat (P < 0.05). MAG supplement reduced the malondialdehyde (MDA) levels, and increased the glutathione (GSH), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC) levels in breast muscle and jejunum. PCR analysis showed that MAG increased the levels of NF-E2-related factor 2 (Nrf2), NAD(P)H/quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), glutathione-S transferase (GST), glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase modifier subunit (GCLM), and SOD expressions (P < 0.05). Analysis of differential enrichment of gut microbiota found that Faecalibacterium in the cecum of MAG supplemented broilers increased, and Coprobacillus has decreased (P < 0.05). In conclusion, MAG improved growth performance, meat quality of the broilers and antioxidant capacity, and modulated gut microbiota homeostasis.

SDTM: A Novel Topic Model Framework for Syndrome Differentiation in Traditional Chinese Medicine.

Syndrome differentiation is the most basic diagnostic method in traditional Chinese medicine (TCM). The process of syndrome differentiation is difficult and challenging due to its complexity, diversity, and vagueness. Recently, artificial intelligent methods have been introduced to discover the regularities of syndrome differentiation from TCM medical records, but the existing DM algorithms failed to consider how a syndrome is generated according to TCM theories. In this paper, we propose a novel topic model framework named syndrome differentiation topic model (SDTM) to dynamically characterize the process of syndrome differentiation. The SDTM framework utilizes latent Dirichlet allocation (LDA) to discover the latent semantic relationship between symptoms and syndromes in mass of Chinese medical records. We also use similarity measurement method to make the uninterpretable topics correspond with the labeled syndromes. Finally, Bayesian method is used in the final differentiated syndromes. Experimental results show the superiority of SDTM over existing topic models for the task of syndrome differentiation.

Effect of Coptis chinensis franch and Magnolia officinalis on intestinal flora and intestinal barrier in a TNBS-induced ulcerative colitis rats model.

BACKGROUND: In folk medicine Coptis chinensis Franch (Huanglian in Chinese, HL) and Magnoliae officinalis (Houpo, HP) have been used to treat gastrointestinal disorders over hundreds of years, such as ulcers and inflammation. PURPOSE: To investigate the therapeutic effects of HL and HP on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced ulcerative colitis (UC) rats, and investigated its effect on the intestinal flora of UC rats. METHOD: TNBS 40 mg/kg was utilized to establish UC model. Rats were sacrificed after gavage for 7 days. Body weight loss, disease activity index (DAI), colonic mucosal damage index (CMDI) and histopathology were measured. Intestinal content samples were collected, and analyzed by 16 S rRNA sequencing. Western blot, immunohistochemistry and real-time polymerase chain reaction were used to evaluate the regulation mechanism of HL+HP in UC model rats. RESULTS: The results showed that the DAI score, CMDI score and histological score were significantly decreased in each group. The symptoms of diarrhea, hematochezia, colonic mucosal injury and congestion and edema were improved. Sequencing results of intestinal flora showed that the abundance of probiotics such as Akkermansia and Blautia was increased in HL group and HL+HP group, while probiotics such as Allobaculum and Alloprevotella were increased in HP group. The intestinal pathogenic bacteria such as Escherichia-Shigella and Clostridium_sensu_stricto_1 were decreased. In addition, HL+HP could also inhibit the inflammatory response and protect the integrity of the tight junction to play an anti-UC effect. CONCLUSION: Coptis chinensis Franch and Magnolia officinalis might prevent intestinal barrier damage by regulating intestinal flora imbalance and inhibit the inflammatory response.

Recent Progress on the Synergistic Antitumor Effect of a Borneol-Modified Nanocarrier Drug Delivery System.

Borneol, a traditional Chinese medicine, can enhance therapeutic efficacy by guiding the active ingredients to the target site. Reportedly, borneol improves the penetration capacity of the nasal, cornea, transdermal, intestinal, and blood-brain barriers. Although nanotechnology dramatically changed the face of oncology by targeting tumor sites, the efficiency of nanoparticles delivered to tumor sites is very low, with only 0.7% of the total particles delivered. Thus, based on the penetration ability and the inhibition drug efflux of borneol, it was expected to increase the targeting and detention efficacy of drugs into tumor sites in nanocarriers with borneol modification. Borneol modified nanocarriers used to improve drug-targeting has become a research focus in recent years, but few studies in this area, especially in the antitumor application. Hence, this review summarizes the recent development of nanocarriers with borneol modification. We focus on the updated works of improving therapeutic efficacy, reducing toxicity, inhibiting tumor metastasis, reversing multidrug resistance, and enhancing brain targeting to expand their application and provide a reference for further exploration of targeting drug delivery systems for solid tumor treatment.

Storax, A Promising Botanical Medicine for Treating Cardio-Cerebrovascular Diseases: A Review.

In recent years, the incidence and mortality of cardio-cerebrovascular diseases have been increasing year by year, which has become global burden and challenge. Based on the holistic thinking of "brain disease affects the heart" and "heart disease affects the brain," as well as the characteristics of multi-target and multi-path effects of Chinese medicine, Chinese medicine is more advantageous in the treatment of cardio-cerebrovascular diseases. As a botanical medicine, storax is known for its resuscitation, filth avoidance and pain-relieving effects in the treatment of cardio-cerebrovascular diseases. By reviewing and collating the relevant domestic and international literature in the past 10 years, we have sorted out an overview of the medicinal parts, traditional uses and chemical composition of storax. For the first time, based on the idea of "cerebral and cardiac simultaneous treatment," the pharmacological activities and mechanisms of heart and brain protection of storax for treating cardio-cerebrovascular diseases were summarized and analyzed, showing that storax has the pharmacological effects of anti-cerebral ischemia, regulation of blood-brain barrier, bidirectional regulation of the central nervous system, anti-myocardial ischemia, anti-arrhythmia, anti-thrombosis and anti-platelet aggregation. It mainly exerts its protective effects on the brain and heart through mechanisms such as inhibition of inflammatory immune factors, anti-oxidative stress, anti-apoptosis, pro-neovascularization and regulation of NO release. On the basis of the current findings and limitations, the future research strategies and perspectives of storax are proposed, with a view to providing a reference for further application and development of this medicine, as well as contributing new thoughts and visions for the clinical application of "treating brain-heart synchronously".

Mathematical model for treatment of neonatal hyperbilirubinemia.

Based on the mechanism of neonatal hyperbilirubinemia treatment methods (light, exchange blood and drugs), three types of neonatal hyperbilirubinemia treatment mathematical models are established, and the expressions of the model solutions are given in this paper. By applying clinical test data and numerical approximation algorithm, the relevant parameters in the model can be estimated. According to the standards of "Expert Consensus", two treatment plans are designed, which are 1) the combined transfusion and phototherapy treatment plan and 2) the combined treatment plan of drugs, transfusion and phototherapy. The results of the program operation are numerically simulated and compared with the treatment data of clinical cases. It is found that the coincidence effect is important, which verified the rationality of the model. The model results can track and predict the changes of bilirubin levels in real-time, which provides a theoretical basis for the clinical design of treatment plans.

Biomimetic nanoparticles loading with gamabutolin-indomethacin for chemo/photothermal therapy of cervical cancer and anti-inflammation.

A pro-nanodrug combinational strategy for efficient cervical cancer therapy with intrinsic tumor microenvironment (TME)-responsive elements and low side effects is highly desired. Here, a pro-nanodrug complexes with GSH and NIR responsive manner is reported to boost gamabufotalin induced chemo-photothermal therapy with the assistance of reprogrammed TME by indomethacin. In addition, hybrid cell membrane was used to endow nanocomplexes with the prolonging circulation time and high accumulation of drug at tumor tissue. Indomethacin activated by the high level GSH can attenuate tumor inflammation microenvironment triggered by PTT and sensitize tumor cells to gamabufotalin through inhibiting PGE2 secretion. The released low-dose gamabufotalin with low side effects can efficiently kill tumor cells by ROS production and COX-2 low expression. In vitro and in vivo assays demonstrated that strong anti-tumor activity of nanocomplexes in tumor-bearing mice through chemo-photothermal therapy, which was reflected by the eradication of cervical tumor and significant extension of survival time of mice.