[Research progress on pathogenic mechanism of sepsis-induced liver injury and treatment with traditional Chinese medicine and its active components].

Sepsis is a systemic inflammatory response syndrome caused by infection, with high morbidity and mortality. Sepsis-induced liver injury(SILI) is one of the manifestations of sepsis-induced multiple organ syndrome. At present, there is no recommended pharmacological intervention for the treatment of SILI. traditional Chinese medicine(TCM), based on the holism and dialectical treatment concept, shows the therapeutic characteristics of multi-target and multi-pathway and can comprehensively prevent and treat SILI by interfering with inflammatory factors, inflammatory signaling pathways, and anti-oxidative stress and inhibiting apoptosis. This article reviewed the experimental studies on the treatment of SILI with TCM to clarify its pathogenic mechanism and therapeutic characteristics, so as to provide more ideas and directions for the development or preparation of new drugs.

Acupoint application therapy alleviates pain by regulating immune function through inhibiting TLR4/MyD88/NF-κB p65 signaling in a primary dysmenorrhea rat model. / 穴位贴敷通过TLR4/MyD88/NF-κBé€šè·¯è°ƒèŠ‚åŽŸå‘æ€§ç—›ç»å¤§é¼ çš„å ç–«åŠŸèƒ½.

OBJECTIVES: To investigate the effects of graphene-based warm uterus acupoint paste on uterine Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear transcription factor-kappa B p65 (NF-κB p65) signaling pathway and Th1/Th2 immune balance in primary dysmenorrhea ( PD ) model rats, so as to reveal its immunological mechanisms of relieving dysmenorrhea. METHODS: Thirty SD female rats were randomly divided into 3 groups：normal group, model group and acupoint paste group, with 10 rats in each group. PD rat model was established by subcutaneous injection of estradiol benzoate for 10 consecutive days. At the same time of modeling, graphene-based warm uterus acupoint paste was applied to the acupoints of "Guanyuan" (CV4), bilateral "Zigong" (EX-CA1) and "Sanyinjiao" (SP6) of rats in the acupoint paste group. The application was continuously applied once daily for 10 d, 5 h each time. On the 11th day, oxytocin was injected intraperitoneally to observe the writhing latency, writhing times within 30 min and writhing score of rats in each group. The spleen and thymus indexes were calculated. The pathological changes of spleen and thymus tissue were observed after HE staining. The contents of serum immunoglobulin (Ig) A, IgG, tumor necrosis factor-α (TNF-α), interleukin (IL)-2, interferon-γ (IFN-γ), IL-4 and IL-10 were detected by ELISA . The protein and mRNA expression levels of TLR4, MyD88 and NF-κB p65 in rat uterine tissue were detected by Western blot and real-time quantitative PCR, respectively. RESULTS: Compared with the normal group, the writhing times and writhing scores within 30 min of rats in the model group were significantly increased(P<0.001), and the rats showed writhing reaction (P<0.01). The spleen index and thymus index were significantly decreased(P<0.01, P<0.05). The spleen and thymus had obvious pathological changes. The contents of IgA, IgG, TNF-α, IL-2 and IFN-γ in serum were significantly increased, while the contents of serum IL-4 and IL-10 were significantly decreased(P<0.001, P<0.01). The expression levels of TLR4, MyD88, NF-κB p65 protein and corresponding mRNA in uterine tissue were significantly increased(P<0.001). Following intervention, compared with the model group, the writhing latency time of rats in the acupoint paste group was prolonged, and the writhing times and writhing scores within 30 min were significantly decreased (P<0.001). The spleen index and thymus index were significantly increased(P<0.01, P<0.05). The pathological changes of spleen and thymus were improved. The contents of serum IgA, IgG, TNF-α, IL-2 and IFN-γ were significantly decreased, while the contents of IL-4 and IL-10 were significantly increased(P<0.001, P<0.05, P<0.01). The expression of TLR4, MyD88, NF-κB p65 protein and the corresponding mRNA levels in uterine tissue were decreased(P<0.001, P<0.01). CONCLUSIONS: Graphene-based warm uterus acupoint paste can regulate the immune balance of Th1/ Th2 by regulating TLR4/ MyD88/ NF-κB p65 signaling pathway, repair the pathological damage of immune tissue, improve immune function, and effectively relieve the pain symptoms of PD rats.

Modulation Mechanism of Wuniuzao Dark Tea Polysaccharide on Lipid Metabolism in Hyperlipidemic Mice Induced by High-Fat Diet.

The aim of this study was to investigate the functional mechanism of Wuniuzao dark tea polysaccharide (WDTP) that protect against hyperlipidemia in mice induced by high-fat diet. WDTP was extracted by hot water, isolated and purified by DEAE-52 chromatography and characterized by high-performance liquid chromatograph (HPLC), Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscope (SEM). Different doses (200 or 800 mg/kg/day) of WDTP were orally administered to mice induced by high-fat diet to evaluate the mechanism of WDTP regulating lipid metabolism. And these results showed that average molecular weight of WDTP was nearly 63,869 Da. And WDTP intervention significantly reduced body weight, lipid accumulation, and modulated blood lipid levels. The mechanism of WDTP ameliorating lipid metabolism was associated with regulating the expression of lipid metabolism-related genes and serum exosomes miR-19b-3p, and modulating the community structure of gut microbiota in mice.

Effects of Fermented Extracts of Wuniuzao Dark Loose Tea on Hepatic Sterol Regulatory Element-Binding Protein Pathway and Gut Microbiota Disorder in Obese Mice.

BACKGROUND: Artificially fermented dark loose tea is a type of novel dark tea prepared via fermentation by Eurotium cristatum. The effects of artificially fermented dark loose tea on lipid metabolism are still unclear. OBJECTIVES: This study aimed to explore if artificially fermented dark loose tea has the same effects as naturally fermented dark loose tea in regulating hepatic lipid metabolism. METHODS: Thirty-six 8-wk-old male C57BL/6 mice were randomly divided into 6 treatment groups, including normal control (NC), high-fat diet (HFD), positive control (PC), Wuniuzao dark raw tea (WDT), Wuniuzao naturally fermented dark loose tea (NFLT), and Wuniuzao artificially fermented dark loose tea (AFLT) groups. The HFD, PC, WDT, NFLT, and AFLT groups were fed a HFD. The PC group was supplemented with atorvastatin (10 mg/kg). The WDT group was supplemented with WDT (300 mg/kg), the NFLT group with NFLT (300 mg/kg), and the AFLT group with AFLT (300 mg/kg). RESULTS: The study compared the effect of WDT, NFLT, and AFLT on liver steatosis and gut microbiota disorder in obese mice. All 3 tea extracts reduced body weight, glucose tolerance, and serum lipid concentrations. Via sterol-regulatory element binding protein (SREBP)-mediated lipid metabolism, all 3 tea extracts alleviated hepatic steatosis in mice with obesity. Furthermore, NFLT and AFLT intervened in the abundance of Firmicutes, Bacteroidetes, Clostridia, Muribaculaceae, and Lachnospiraceae. CONCLUSION: In mice with obesity induced by a HFD, WDT, NFLT, and AFLT may improve hepatic steatosis through an SREBP-mediated lipid metabolism. Moreover, NFLT and AFLT improved the composition of gut microbiota.

Theabrownin from Wuniuzao Dark Tea Regulates Hepatic Lipid Metabolism and Gut Microbiota in Mice Fed High-Fat Diet.

The search for functional foods with no side effects that can alleviate obesity has been a common trend. Wuniuzao dark tea could be a safe choice. This study aimed to explore whether theabrownin from Wuniuzao dark tea could regulate hepatic lipid metabolism and gut microbiota in mice fed a high-fat diet. In total, fifty 8-week-old male C57BL/6 mice were randomly divided into five treatment groups, including a normal control group, high-fat diet group, positive control group, low-dose theabrownin group, and high-dose theabrownin group. After a 9-week intervention, these mice were selected from each treatment group for sampling. The results showed that the body weight and epididymis fat weight of obese mice fed with theabrownin were decreased. Serum total triglycerides, total cholesterol, and low-density lipoprotein cholesterol, and activities of aspartate aminotransferase and alanine aminotransferase were also decreased. Protein and mRNA expression of fatty acid synthesis and lipid production-related genes of mice fed with theabrownin were downregulated. The gut microbiota composition in the theabrownin group was improved. The study indicated that theabrownin from Wuniuzao dark tea could achieve the liver protection and anti-obesity effects by regulating the Srebp lipid metabolism pathway and bile acid metabolism process, and improving the gut microbiota composition of mice.

Protective effect of electroacupuncture at ST36 against damage of intestinal mucosa, oxidative stress and apoptosis induced by 5-FU chemotherapy in mice with colon cancer. / 电针"足三里"å‡è½»å¤§è‚ ç™Œå°é¼ åŒ–ç–—åŽè‚ é»è†œæŸä¼¤åŠå ¶å¯¹æ°§åŒ–åº”æ¿€å’Œç»†èƒžå‡‹äº¡çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) at "Zusanli"(ST36) on intestinal mucosal damage, intestinal mucosal oxidative stress injury and apoptosis induced by 5-fluorouraeil (5-FU) chemotherapy in colorectal cancer-bearing mice. METHODS: Thirty male BALB/c mice were randomly divided into normal control, colorectal cancer (CT26), 5-FU, non-acupoint and ST36 groups, with 6 mice in each group. Except for those of the normal control group, mice of the remaining 4 groups received subcutaneous implantation of colorectal CT26 cell suspension (0.1 mL) in the right armpit for establishing colorectal cancer model. Rats of the 5-FU group, non-acupoint group and ST36 group were given with 5 mg/mL 5-FU solution once every 3 days for a total of 21 days. For mice of the non-acupoint group and ST36 group, EA (2 Hz, 1-2 mA) was applied to bilateral ST36 or non-acupoints (the bilateral sunken spots about 3 mm to the midpoint between the tail root and the anus) for 5 min after each intraperitoneal infusion of 5-FU, once every 3 days, for a total of 21 days. After the intervention, the diarrhea index was assessed. The length of colon (from the endpoint of cecum to the anal orifice) was measured. Histopathological changes of colonic mucosa were observed by H.E. staining, and the length of colonic villi was measured. The content of malondialdehyde (MDA), and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of colonic tissue were detected by thibabituric acid, xanthine oxidase and colorimetric method, respectively. The rate of cell apoptosis in the colonic tissue was measured by TUNEL assay. The positive expressions of Bax and Bcl-2 in colonic tissue were determined by immunohistochemistry. RESULTS: The CT26 model group didn't show any significant changes in the diarrhea index, colon length, colon villus length, MDA content, SOD and GSH-Px activities, colonic cell apoptosis rate, and Bax and Bcl-2 expression levels when compared with the normal group. Compared with the CT26 group, the 5-FU group had a remarkable increase in the diarrhea index, MDA content, colonic cell apoptosis rate and Bax expression level (P<0.01, P<0.05), and a marked decrease in the colon length, colon villus length, SOD and GSH-Px activities and Bcl-2 expression level (P<0.01), suggesting the side effects of administration of 5-FU. Compared with the 5-FU group, the diarrhea index, MDA content, colonic cell apoptosis rate and Bax expression level were markedly decreased (P<0.05, P<0.01) and those of the colon length, colon villus length, SOD and GSH-Px activities and Bcl-2 expression level were obviously increased (P<0.01) in the ST36 group. Compared with the 5-FU group, the non-acupoint group also had an increase in the colon villus length, SOD and GSH-Px activities (P<0.01, P<0.05) and a decrease in the cell apoptosis rate (P<0.01). CONCLUSIONS: EA at ST36 has a positive effect in reducing intestinal mucosal damage induced by 5-FU chemotherapy in cancer-bearing mice, which may be related to its function in relieving oxidative stress injury and inhibiting apoptosis of colonic tissue.

Acupoint compatibility effect: increasing "effect value" and expanding "effect domain". / è §ç©´é ä¼æ•ˆåº”.

By summarizing and exploring the theoretic connotation, key of functions and effect mechanism of acupoint compatibility, the effect of acupoint compatibility is concluded as the increase of "effect value" and the expansion of "effect domain". The increase of "effect value" is the concrete embodiment by the value of medical assessment scale, the value of objective index detection in clinical trial and the value of index detection in experiment research. The expansion of "effect domain" is the increase of effect target and the extension of effect scope. The paper interprets the scientific connotation of acupoint compatibility therapy from a new perspective, and emphasizes the innovative approaches to research while bringing forth new ideas on the research method. It is anticipated that a novel breakthrough can be achieved in the study of acupoint compatibility and the improvement of acupuncture-moxibustion efficacy.

Genotype-Controlled Vertical Transmission Exerts Selective Pressure on Community Assembly of Salvia miltiorrhiza.

The plant's endophytic fungi play an important role in promoting host development and metabolism. Studies have shown that the factors affecting the assembly of the endophyte community mainly include host genotype, vertical transmission, and soil origin. However, we do not know the role of vertically transmitted endohytic fungi influences on the host-plant's endophytic community assembly. Salvia miltiorrhiza from three production areas were used as research objects; we constructed three production area genotypes of S. miltiorrhiza regenerated seedlings simultaneously. Based on high-throughput sequencing, we analyzed the effects of genotype, soil origin, and vertical transmission on endophytic fungal communities. The results show that the community of soil origins significantly affected the endophytic fungal community in the regenerated seedlings of S. miltiorrhiza. The influence of genotype on community composition occurs through a specific mechanism. Genotype may selectively screen certain communities into the seed, thereby exerting selection pressure on the community composition process of offspring. As the number of offspring increases gradually, the microbiota, controlled by genotype and transmitted vertically, stabilizes, ultimately resulting in a significant effect of genotype on community composition.Furthermore, we observed that the taxa influencing the active ingredients are also selected as the vertically transmitted community. Moreover, the absence of an initial vertically transmitted community in S. miltiorrhiza makes it more vulnerable to infection by pathogenic fungi. Therefore, it is crucial to investigate and comprehend the selection model of the vertically transmitted community under varying genotypes and soil conditions. This research holds significant implications for enhancing the quality and yield of medicinal plants and economic crops.

Therapeutic effects of tea polyphenol-loaded nanoparticles coated with platelet membranes on LPS-induced lung injury.

Patients with ALI (acute lung injury)/ARDS (acute respiratory distress syndrome) are often septic and with poor prognosis, which leads to a high mortality rate of 25-40%. Despite the advances in medicine, there are no effective pharmacological therapies for ALI/ARDS due to the short systemic circulation and poor specificity in the lungs. To address this problem, we prepared TP-loaded nanoparticles (TP-NPs) through the emulsification-and-evaporation method, and then the platelet membrane vesicles were extracted and coated onto the surface of the NPs to constitute the biomimetic PM@TP-NPs. In a LPS-induced ALI mouse model, PM@TP-NPs showed good biocompatibility and biosafety, which was evidenced by no significant toxic effect on cell viability and no hemolysis of red blood cells. In ALI mice, the PM@TP-NPs showed favorable anti-inflammation and enhanced therapeutic activity of TPs compared to the free drug. Administration of PM@TP-NPs effectively inhibited lung vascular injury, evidenced by the decreased lung vascular permeability, reduced pro-inflammatory cytokine burden, evidenced by decreased inflammatory cell (macrophages, neutrophils, etc.) infiltration in the bronchoalveolar lavage fluid (BALF) and lung tissues, and inhibited the secretion of pro-inflammatory cytokines and NLRP3 inflammasome activation. ALI/ARDS is defined by damage to the alveolar epithelium and endothelium; thus, effective intervention targeting pulmonary vascular endothelial cells (VECs) is crucial for the treatment of respiratory diseases. For further determination of the targeting of PM cloaked NPs, healthy mice were also administered with the same NPs. Interestingly, the PM cloaked NPs only showed highly efficient targeting to the inflamed lungs and VECs, but no accumulation in healthy lungs and VECs. The data demonstrated that this biomimetic nanoplatform could be used as a potential strategy for personalized therapies in the treatment of inflammatory diseases, such as ALI/ARDS, and even COVID-19-associated pneumonia.

Association of Nonpuerperal Mastitis with Cytokines Related to Helper T Cells TH1/TH2 and TH17/Treg.

Objective: To investigate the association of nonpuerperal mastitis with cytokines related to the helper T cells TH1/TH2 and TH17/Treg and associated immune balance. Methods: From 2016 to 2021, we included 40 patients with non-puerperal mastitis who underwent surgery at China-Japan Friendship Hospital and compared them with 40 control patients with benign non-infectious breast disease. Hematoxylin-eosin staining detects inflammatory infiltrates of breast tissue. The expression of interferon γ and interleukin 4 in breast tissue was detected by immunofluorescence imaging, and the relative protein expression of TH1/TH2 and TH17/Treg cell-associated cytokines in CD4+ T cells was detected by western blotting. CD4+ T cells were isolated by fluorescence-activated cell sorting for detection of the relative protein expression of interferon γ and interleukin 4 in CD4+ T cells. Results: Hematoxylin-eosin staining showed that the nonpuerperal mastitis group had significantly greater inflammatory infiltration than the control group. Immunofluorescence images showed the relative fluorescence intensity of interferon γ was significantly higher in the nonpuerperal mastitis group than in the control group (P < .001), but the relative fluorescence intensity of interleukin 4 did not significantly differ between the 2 groups (P = .0686). Western blotting revealed that the relative protein expression of interferon γ, interleukin 2, and interleukin 17 was significantly higher in the nonpuerperal mastitis group than in the control group (P < .001), but the relative protein expression of interleukin 4 (P = .0512), interleukin 10 (P = .3088), and transforming growth factor ß (P = .0653) did not significantly differ between the 2 groups. Flow cytometry of isolated CD4+ T cells showed the relative protein expression of interferon γ was significantly higher in the nonpuerperal mastitis group than in the control group (P < .001), but the relative protein expression of interleukin 4 did not significantly differ between the 2 groups (P = .0680). Conclusion: The expression of the TH1 cytokines interferon γ and interleukin 2 and the TH17 cytokine interleukin 17 was significantly higher in patients with nonpuerperal mastitis, while the TH2 cytokine interleukin 4 and the Treg cytokines interleukin 10 and transforming growth factor ß were expressed at lower levels. This study provides new research ideas for the treatment of mastitis.

Polysaccharides Derived from Mushrooms in Immune and Antitumor Activity: A Review.

Mushrooms are full of nutrition and have beneficial properties for human health. Polysaccharides are the main component of edible and medicinal mushrooms, especially ß-glucans, which have attracted much more attention for their complex structure and diverse biological activities. Among all the diverse medicinal activities of mushroom polysaccharides, antitumor and immune-enhancing activities are two excellent bioactivities that have much more potential and deserve application. Their bioactivities are highly dependent on their structural features, including molecular weight, monosaccharide composition, degree of branching, type and configuration of glycosidic bonds, substituent pattern, and chain conformation. This review summarizes the current method for obtaining polysaccharides from mushrooms, chemical characterizations of the structures and their roles in immune and antitumor activities. In addition, the methods for preparation of the polysaccharide derivatives and the potential medicinal clinical application are also discussed in this review, which may provide new guidance for mushroom polysaccharide development.

Meta-analysis of the results of haploidentical transplantation in the treatment of aplastic anemia.

This meta-analysis was to evaluate the outcome of haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) for aplastic anemia (AA) compared with matched related donor (MRD)-HSCT, matched unrelated donor (MUD)-HSCT, and immunosuppressive therapy (IST). Pubmed, Embase, Cochrane Library, Web of Science, CNKI, WanFang, and VIP databases were searched for relevant studies from inception to 22 June 2022. Relative risk (RR) was used to indicate the effect indicator, with a 95% confidence interval (CI) being applied to express the effect size. A subgroup analysis based on the literature quality (low, fair, and high) was applied. Totally, 25 studies were included in this study, comprising 2252 patients. Our findings demonstrated no difference between Haplo-HSCT and MRD-HSCT in 1-, 2-, and 3-year overall survival (OS), failure-free survival (FFS), and engraftment. However, Haplo-HSCT had higher incidences of II-IV acute graft-versus-host disease (aGVHD), chronic GVHD (cGVHD), and cytomegalovirus infection. There were no differences in 3- and 5-year OS, 3-year FFS, platelet engraftment, graft failure (GF), II-IV grade of aGVHD, and complication between Haplo-HSCT and MUD-HSCT; however, Haplo-HSCT had a lower incidence of cGVHD. Compared with IST, Haplo-HSCT had a higher 3-year FFS and 3- and 6-month response rate. However, there were no differences in 3- and 5-year OS, and 12-month response rate between Haplo-HSCT and IST. This study suggests that Haplo-HSCT may be a realistic therapeutic option for AA, which may provide a reference for decision-making.

The ethanol extract of Scutellaria baicalensis Georgi attenuates complete Freund's adjuvant (CFA)-induced inflammatory pain by suppression of P2X3 receptor.

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria baicalensis Georgi (SBG) is a perennial herb with anti-inflammatory, antibacterial, and antioxidant activities, which is traditionally used to treat inflammation of respiratory tract and gastrointestinal tract, abdominal cramps, bacterial and viral infections. Clinically, it is often used to treat inflammatory-related diseases. Research has shown that the ethanol extract of Scutellaria baicalensis Georgi (SGE) has anti-inflammatory effect, and its main components baicalin and baicalein have analgesic effects. However, the mechanism of SGE in relieving inflammatory pain has not been deeply studied. AIM OF THE STUDY: This study aimed to evaluate the analgesic effect of SGE on complete Freund's adjuvant (CFA)-induced inflammatory pain rats, and to investigate whether its effect on relieving inflammatory pain is associated with regulation of P2X3 receptor. MATERIALS AND METHODS: The analgesic effects of SGE on CFA-induced inflammatory pain rats were evaluated by measuring mechanical pain threshold, thermal pain threshold, and motor coordination ability. The mechanisms of SGE in relieving inflammatory pain were explored by detecting inflammatory factors levels, NF-κB, COX-2 and P2X3 expression, and were further verified by addition of P2X3 receptor agonist (α, ß me-ATP). RESULTS: Our results revealed that SGE can notably increase the mechanical pain threshold and thermal pain threshold of CFA-induced inflammatory pain rats, and markedly alleviate the pathological damage in DRG. SGE could suppress the release of inflammatory factors including IL-1ß, IL-6, TNF-α and restrain the expression of NF-κB, COX-2 and P2X3. Moreover, α, ß me-ATP further exacerbated the inflammatory pain of CFA-induced rats, while SGE could markedly raise the pain thresholds and relieve inflammatory pain. SGE could attenuate the pathological damage, inhibit P2X3 expression, inhibit the elevation of inflammatory factors caused by α, ß me-ATP. SGE can also inhibit NF-κB and ERK1/2 activation caused by α, ß me-ATP, and inhibit the mRNA expression of P2X3, COX-2, NF-κB, IL-1ß, IL-6 and TNF-α in DRG of rats induced by CFA coupled with α, ß me-ATP. CONCLUSIONS: In summary, our research indicated that SGE could alleviate CFA-induced inflammatory pain by suppression of P2X3 receptor.

Linoleic acid ameliorates intestinal mucosal barrier injury in early weaned pigeon squabs (Columba livia).

The study aimed to investigate whether linoleic acid could improve the intestinal barrier function of squabs under weaning stress conditions. Totally 320 7-d-old weaned squabs were randomly divided into four treatment groups, including control group (CON), 0.7% linoleic acid addition group (LA007), 1.4% linoleic acid addition group (LA014) and 2.1% linoleic acid addition group (LA021). At 21 d, eight squabs were randomly selected from each treatment group for sampling and determination. The results showed that adding linoleic acid could improve (P < 0.05) the body weight of weaned squabs, and LA014 had the best effect. With the increase of linoleic acid dosage, villi height and villi area increased linearly or quadratically (P < 0.05), and reached the maximum in LA021 or LA014, respectively. The linoleic acid supplementation could improve the intestinal tight junction of weaned squabs, and the LA014 was the most significant (P < 0.05). With the linoleic acid increasing, the levels of intestinal IL-6 and TNF-α decreased linearly (P < 0.05), while intestinal IL-10 increased quadratically (P < 0.05) and reached the maximum in LA014. Serum endotoxin and diamine oxidase levels decreased linearly (P < 0.05) and reached the lowest level in LA014. The ultrastructure of villi revealed that the length of ileal microvilli in LA014 was significantly increased (P < 0.05) and the microvilli became dense, and the mitochondria in epithelial cells returned to normal state. Further exploring the mechanism of linoleic acid alleviating intestinal injury caused by weaning stress in squabs, it was found that linoleic acid down-regulated (P < 0.05) the relative protein expression of TLR4, MyD88, phosphorylated JNK, and phosphorylated p38, reducing secretion of pro-inflammatory factors IL-6 and TNF-α. This study indicated that linoleic acid could alleviate intestinal barrier injury of early weaned squabs by down-regulating TLR4-MyD88-JNK/p38-IL6/TNF-α pathway.

Artificial feeding of early weaned squabs can reduce the burden of breeding pigeons and shorten the breeding cycle. However, similar to early weaned mammals, early weaned squabs would also inevitably undergo severe physiological and psychological stress responses in the early stage. The growth performance and immunity of early weaned squabs were inferior to those of the parent feeding squabs. Previous studies suggest that linoleic acid played an important role in the growth and development of squabs. Therefore, the study aimed to investigate whether linoleic acid could improve the intestinal barrier function of squabs under weaning stress conditions. Totally 320 7-d-old weaned squabs were randomly divided into four treatment groups, including control group and linoleic acid addition groups with three different doses. At 21 d, eight squabs were randomly selected from each treatment group for sampling and determination. The results indicated that under weaning stress conditions, linoleic acid could weaken the inflammatory response, and alleviate the intestinal epithelial barrier damage of weaned squabs, specifically by promoting the development of intestinal villi, strengthening the tight junction, reducing intestinal permeability, and promoting the secretion of anti-inflammatory factors.

An efficient high-speed counter-current chromatography method for the preparative separation of sesquiterpenoids from the rhizomes of Cyperus rotundus L. combined with evaluation of the anti-inflammation activity in vitro and molecular docking.

Cyperus rotundus L. has been extensively used in ancient medication for the treatment of different disorders worldwide, in which sesquiterpenes are the most representative components. In this study, sesquiterpenes were effectively purified by two-dimensional counter-current chromatography in combination with continuous injection and inner-recycling mode with a solvent system of n-hexane/ethyl acetate/methanol/water (1:0.2:1:0.2, v/v/v/v). For one-dimension separation, continuous injection mode was used with three times injection and the inner-recycling mode was adopted for the separation of two mixtures for two-dimensional separation. Finally, four sesquiterpenoids, including scariodione (1), cyperenoic acid (2), scariodione (3), and α-cyperone (4), were obtained with purities over 98%. Mass spectrometry and nuclear magnetic resonance were applied to identify their structures. The results from the anti-inflammation effect with zebrafish demonstrated that cyperenoic acid exhibited stronger anti-inflammation activity. Molecular docking results suggested that cyperenoic acid possessed lower binding energies -9.4545 kcal/mol with 1CX2 to form formed hydrogen bond interaction with ARG120. In general, all the obtained findings proved that the strong anti-inflammation capacity of cyperenoic acid can have the potential of being adopted for treating diseases resulting from inflammation.

HIF2α activation and mitochondrial deficit due to iron chelation cause retinal atrophy.

Iron accumulation causes cell death and disrupts tissue functions, which necessitates chelation therapy to reduce iron overload. However, clinical utilization of deferoxamine (DFO), an iron chelator, has been documented to give rise to systemic adverse effects, including ocular toxicity. This study provided the pathogenic and molecular basis for DFO-related retinopathy and identified retinal pigment epithelium (RPE) as the target tissue in DFO-related retinopathy. Our modeling demonstrated the susceptibility of RPE to DFO compared with the neuroretina. Intriguingly, we established upregulation of hypoxia inducible factor (HIF) 2α and mitochondrial deficit as the most prominent pathogenesis underlying the RPE atrophy. Moreover, suppressing hyperactivity of HIF2α and preserving mitochondrial dysfunction by α-ketoglutarate (AKG) protects the RPE against lesions both in vitro and in vivo. This supported our observation that AKG supplementation alleviates visual impairment in a patient undergoing DFO-chelation therapy. Overall, our study established a significant role of iron deficiency in initiating DFO-related RPE atrophy. Inhibiting HIF2α and rescuing mitochondrial function by AKG protect RPE cells and can potentially ameliorate patients' visual function.

Synergistic antibacterial activity of baicalin and EDTA in combination with colistin against colistin-resistant Salmonella.

The emergence and rapid spread of multidrug resistant (MDR) Gram-negative bacteria have posed a serious threat to global health and security. Because of the time-consuming, high cost and high risk of developing new antibiotics, a significant method is to use antibiotic adjuvants to revitalize the existing antibiotics. The purpose of the study is to research the traditional Chinese medicine baicalin with the function of inhibiting the efflux pump and EDTA whether their single or combination can increase the activity of colistin against colistin-resistant Salmonella in vitro and in vivo, and to explore its molecular mechanisms. In vitro antibacterial experiments, we have observed that baicalin and EDTA alone could enhance the antibacterial activity of colistin. At the same time, the combination of baicalin and EDTA also showed a stronger synergistic effect on colistin, reversing the colistin resistance of all Salmonella strains. Molecular docking and RT-PCR results showed that the combination of baicalin and EDTA not only affected the expression of mcr-1, but also was an effective inhibitor of MCR-1. In-depth synergistic mechanism analysis revealed that baicalin and EDTA enhanced colistin activity through multiple pathways, including accelerating the tricarboxylic acid cycle (TCA cycle), inhibiting the bacterial antioxidant system and lipopolysaccharide (LPS) modification, depriving multidrug efflux pump functions and attenuating bacterial virulence. In addition, the combinational therapy of colistin, baicalin and EDTA displayed an obvious reduction in bacterial loads cfus of liver and spleen compared with monotherapy and 2-drug combination therapy. In conclusion, our study indicates that the combination of baicalin and EDTA as a novel colistin adjuvant can provide a reliable basis for formulating the therapeutic regimen for colistin resistant bacterial infection.

Transcriptomics and metabolomics reveal the role of CYP1A2 in psoralen/isopsoralen-induced metabolic activation and hepatotoxicity.

Psoralen and isopsoralen are the pharmacologically important but hepatotoxic components in Psoraleae Fructus. The purpose of this study was to reveal the underlying mechanism of psoralen/isopsoralen-induced hepatotoxicity. Initially, we applied integrated analyses of transcriptomic and metabolomic profiles in mice treated with psoralen and isopsoralen, highlighting the xenobiotic metabolism by cytochromes P450 as a potential pathway. Then, with verifications of expression levels by qRT-PCR and western blot, affinities by molecular docking, and metabolic contributions by recombinant human CYP450 and mouse liver microsomes, CYP1A2 was screened out as the key metabolic enzyme. Afterwards, CYP1A2 induction and inhibition models in HepG2 cells and mice were established to verify the role of CYP1A2, demonstrating that induction of CYP1A2 aggravated the hepatotoxicity, and conversely inhibition alleviated the hepatotoxic effects. Additionally, we detected glutathione adducts with reactive intermediates of psoralen and isopsoralen generated by CYP1A2 metabolism in biosystems of recombinant human CYP1A2 and mouse liver microsomes, CYP1A2-overexpressed HepG2 cells, mice livers and the chemical reaction system using UPLC-Q-TOF-MS/MS. Ultimately, the high-content screening presented the cellular oxidative stress and relevant hepatotoxicity due to glutathione depletion by reactive intermediates. In brief, our findings illustrated that CYP1A2-mediated metabolic activation is responsible for the psoralen/isopsoralen-induced hepatotoxicity.

Identification of the antidepressant fraction and its major chemical constituents of Radix Paeoniae Alba / 药学学报

The goal of this work was to investigate the antidepressant fraction from Radix Paeoniae Alba and identify its major chemical constituents. Corticosterone injured rat phaeochromocytoma (PC12) cells and behavioral despair depression models of mice were used to evaluate the antidepressant effects of Radix Paeoniae Alba (Bai-Shao) ethanol extract (BS-E) and its three fractions (BS-10E, BS-60E, BS-95E) isolated by macroporous resin column chromatography. Animal experimental procedures were approved by the Animal Ethics Committee of the Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College (approval No.: SLXD-20210618051). The results showed that BS-E, BS-10E and BS-60E had protective effects against PC12 cells injury induced by corticosterone, among which BS-60E had the strongest protective effect. BS-60E could significantly shorten the time of forced swimming and tail suspension in despair depression models of mice, and was identified as the antidepressant fraction of Radix Paeoniae Alba. The major chemical constituents in the antidepressant fraction were identified by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), and their proposed fragmentation pathways in MS spectra were deduced. A total of 79 chemical constituents were identified from BS-60E, including 36 monoterpenes, 34 polyphenols, 6 oligosaccharides, and 3 other constituents, and monoterpenes and polyphenols may be major effective constituents of BS-60E.

Global attitudes on and the status of enteral nutrition therapy for pediatric inflammatory bowel disease.

Enteral nutrition (EN) is a diet-remission therapy for inflammatory bowel disease (IBD) that plays a more important role in children than adults. EN includes exclusive enteral nutrition (EEN), partial enteral nutrition (PEN), and maintenance enteral nutrition (MEN). However, EEN remains an unstandardized treatment for pediatric IBD. The types and methods of EN differ around the world. The current study reviewed the EN literature on children with IBD. A total of 12 survey studies were identified that analyzed the current state of EN use, including clinical opinions, implementation methods, treatment course, EEN formula, IBD classification, progress, dietary reintroduction, and patient feedback. The findings revealed that EEN has a strong effect on mild to moderate Crohn's disease (CD). The usage rates of this treatment in different sites were ileum/colon (Paris classification L3) > ileum (L1) > upper digestive tract (L4) > colon (L2) > perianal disease (P) > ulcerative colitis (UC) > extraintestinal lesions. The polymeric formula was the most used EN formulation. New EN diets include a CD exclusion diet (CDED), a specific carbohydrate diet (SCD), and a CD treatment-with-eating (CD-TREAT) diet. Children with IBD responded similarly to EEN administered orally or using a feeding tube. Most guidelines recommended 6-8 weeks of EEN treatment to induce remission. Many clinicians preferred to combine drug medications during EEN and recommended that MEN accounts for at least 25-35% of daily caloric intake. EN remains an unstandardized therapy that requires teamwork across disciplines.