A Rare Case of Benign Recurrent Intrahepatic Cholestasis Initially Diagnosed in Middle-age.

Background: Repeated episodes of jaundice and pruritus are common in a group of autosomal recessive liver diseases known as benign recurrent intrahepatic cholestasis. Benign recurrent intrahepatic cholestasis (BRIC) is divided into two types, type 1 and type 2, and is caused by mutations in the ATP8B1 and ABCB11 genes. Here, we report a rare case of BRIC type 2 mutation. Case presentation: A 45-year-old Chinese man had three frequent episodes of jaundice marked by extensive excoriation and severe pruritis, although he had no prior history of jaundice. Laboratory investigations showed no evidence of liver damage caused by viral, autoimmune, or acquired metabolic etiologies. The CT scan revealed an enlarged gallbladder with numerous punctate high-density shadows, while no wall thickening was observed. Endoscopic ultrasonography showed no evidence of dilation of the intrahepatic and extrahepatic bile duct, as well as the absence of gallstone. Diagnostic evaluation: Immunohistochemical examinations of liver biopsy samples showed cytokeratin-7 positive hepatocytes, suggesting chronic intrahepatic cholestasis. The reticulin fiberstaining demonstrated that the portions of the hepatic plate in the center of the lobule were asymmetrically organized,and somewhat enlarged, with collapsed areas indicating intralobular inflammation. Moreover, there were areas of collapse that indicated the presence of intralobular inflammation. Whole exome sequencing revealed mutations in the ABCB11 gene; c.3084A>G, p.A1028A homozygous mutation (chr2-169789016), and c.2594C>T, p.A865V heterozygous mutation (chr2-169801131). Based on these findings, the final diagnosis of the patient was metabolism-related jaundice. Treatment: Apart from receiving tapering dosage of prednisone to lower bilirubin levels, the patient received no extra care. Conclusion: The comprehensive diagnosis of a middle-aged male patient with BRIC-2, which involved extensive radiological, hematological, and genetic investigations, informed a tailored tapering prednisone regimen, highlighting the importance of personalized medicine in managing atypical presentations of this rare cholestatic disorder.

Matrine reduced intestinal stem cell damage in eimeria necatrix-infected chicks via blocking hyperactivation of Wnt signaling.

BACKGROUND: Coccidiosis is a rapidly spreading and acute parasitic disease that seriously threatening the intestinal health of poultry. Matrine from leguminous plants has anthelmintic and anti-inflammatory properties. PURPOSE: This assay was conducted to explore the protective effects of Matrine and the AntiC (a Matrine compound) on Eimeria necatrix (EN)-infected chick small intestines and to provide a nutritional intervention strategy for EN injury. STUDY DESIGN: The in vivo (chick) experiment: A total of 392 one-day-old yellow-feathered broilers were randomly assigned to six groups in a 21-day study: control group, 350 mg/kg Matrine group, 500 mg/kg AntiC group, EN group, and EN + 350 mg/kg Matrine group, EN + 500 mg/kg AntiC group. The in vitro (chick intestinal organoids, IOs): The IOs were treated with PBS, Matrine, AntiC, 3 µM CHIR99021, EN (15,000 EN sporozoites), EN + Matrine, EN + AntiC, EN + Matrine + CHIR99021, EN + AntiC + CHIR99021. METHODS: The structural integrity of chicks jejunal crypt-villus axis was evaluated by hematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM). And the activity of intestinal stem cells (ISCs) located in crypts was assessed by in vitro expansion advantages of a primary in IOs model. Then, the changes of Wnt/ß-catenin signaling in jejunal tissues and IOs were detected by Real-Time qPCR,Western blotting and immunohistochemistry. RESULTS: The results showed that dietary supplementation with Matrine or AntiC rescued the jejunal injury caused by EN, as indicated by increased villus height, reduced crypt hyperplasia, and enhanced expression of tight junction proteins. Moreover, there was less budding efficiency of the IOs expanded from jejunal crypts of chicks in the EN group than that in the Matrine and AntiC group, respectively. Further investigation showed that AntiC and Matrine inhibited EN-stimulated Wnt/ß-catenin signaling. The fact that Wnt/ß-catenin activation via CHIR99021 led to the failure of Matrine and AntiC to rescue damaged ISCs confirmed the dominance of this signaling. CONCLUSION: Our results suggest that Matrine and AntiC inhibit ISC proliferation and promote ISC differentiation into absorptive cells by preventing the hyperactivation of Wnt/ß-catenin signaling, thereby standardizing the function of ISC proliferation and differentiation, which provides new insights into mitigating EN injury by Matrine and AntiC.

A randomized double-blind clinical trial: Comparison of oclacitinib with a traditional Chinese herbal medicine product (Dihuang Guiqin capsule) in the treatment of canine atopic dermatitis.

Canine atopic dermatitis (cAD) is a common chronic inflammatory skin disease, which seriously affects the quality of life for both dogs and their owners. Currently, the common therapeutic drugs in the clinic have disadvantages such as obvious adverse effects and high prices. Traditional Chinese herbal medicine (TCHM) has great potential for the treatment of cAD. The aim of this study is to compare the effects of different doses of the TCHM product (Dihuang Guiqin capsule) and oclacitinib in the treatment of cAD through a randomized, double-blind trial. Sixty dogs diagnosed with AD were randomly and evenly divided into four groups (n = 15). The TCHM treatment group consisted of three subgroups that received three different oral doses (20, 40, and 60 mg/kg BW), while the control group received 0.5 mg/kg BW of oclacitinib. Each group was administered twice daily for 14 consecutive days. The results showed that both TCHM and oclacitinib significantly improved cAD-induced itching (evaluated by pVAS) and skin lesions (evaluated by CADESI-04), while interleukin 31 (IL-31) concentrations decreased significantly (P < 0.05) and serum biochemical indicators returned to normal. In particular, The therapeutic effects of TCHM medium- and high-dose groups were similar to those of oclacitinib (P > 0.05). The preliminary recommended dose of Dihuang Guiqin capsule for the treatment of cAD has been determined to be 40-60 mg/kg BW twice daily for 14 consecutive days, which can be reduced to once daily as appropriate. Dihuang Guiqin capsule was safe and well tolerated, which may be a new option for the treatment of cAD.

[Liver targeting of compound liposomes mediated by glycyrrhetinic acid derivative receptor and its effect on hepatic stellate cells].

The 3-succinate-30-stearyl glycyrrhetinic acid(18-GA-Suc) was inserted into glycyrrhetinic acid(GA)-tanshinone Ⅱ_A(TSN)-salvianolic acid B(Sal B) liposome(GTS-lip) to prepare liver targeting compound liposome(Suc-GTS-lip) mediated by GA receptors. Next, pharmacokinetics and tissue distribution of Suc-GTS-lip and GTS-lip were compared by UPLC, and in vivo imaging tracking of Suc-GTS-lip was conducted. The authors investigated the effect of Suc-GTS-lip on the proliferation inhibition of hepatic stellate cells(HSC) and explored their molecular mechanism of improving liver fibrosis. Pharmacokinetic results showed that the AUC_(Sal B) decreased from(636.06±27.73) µg·h·mL~(-1) to(550.39±12.34) µg·h·mL~(-1), and the AUC_(TSN) decreased from(1.08±0.72) µg·h·mL~(-1) to(0.65±0.04) µg·h·mL~(-1), but the AUC_(GA) increased from(43.64±3.10) µg·h·mL~(-1) to(96.21±3.75) µg·h·mL~(-1). The results of tissue distribution showed that the AUC_(Sal B) and C_(max) of Sal B in the liver of the Suc-GTS-lip group were 10.21 and 4.44 times those of the GTS-lip group, respectively. The liver targeting efficiency of Sal B, TSN, and GA in the Suc-GTS-lip group was 40.66%, 3.06%, and 22.08%, respectively. In vivo imaging studies showed that the modified liposomes tended to accumulate in the liver. MTT results showed that Suc-GTS-lip could significantly inhibit the proliferation of HSC, and RT-PCR results showed that the expression of MMP-1 was significantly increased in all groups, but that of TIMP-1 and TIMP-2 was significantly decreased. The mRNA expressions of collagen-I and collagen-Ⅲ were significantly decreased in all groups. The experimental results showed that Suc-GTS-lip had liver targeting, and it could inhibit the proliferation of HSC and induce their apoptosis, which provided the experimental basis for the targeted treatment of liver fibrosis by Suc-GTS-lip.

Functional identification of ZDS gene in apple (Malus halliana) and demonstration of it's role in improving saline-alkali stress tolerance.

Carotenoids are powerful antioxidants that mediate transfer of electrons, directly affect abiotic stress responses in plants through regulating activity of antioxidant enzymes. ζ-Carotene desaturase (ZDS) is a key enzyme in carotenoid biosynthesis pathway, which can catalyze ζ-carotene to form lycopene to regulate carotenoid biosynthesis and accumulation. However, the mechanism of its regulation of saline-alkali stress remains unclear. In this research, based on transcriptomic analysis of Malus halliana with a apple rootstock, we screened out ZDS gene (LOC103451012), with significantly high expression by saline-alkali stress, whose expression in the leaves was 10.8-fold than that of the control (0 h) under 48 h of stress. Subsequently, the MhZDS gene was isolated from M. halliana, and transgenic Arabidopsis thaliana, tobacco, and apple calli were successfully obtained through agrobacterium-mediated genetic transformation. We found that overexpression of MhZDS enhanced the tolerance of A. thaliana, tobacco and apple calli under saline-alkali stress and caused a variety of physiological and biochemical changes: compared with wild-type, transgenic plants grew better under saline stress and MhZDS-OE lines showed higher chlorophyll content, POD, SOD, CAT activities and proline content, lower electrical conductivity and MDA content. These results indicate that MhZDS plays an important role in plant resistance to saline-alkali stress, providing excellent resistance genes for the regulatory network of salinity stress response in apples and provide a theoretical basis for the breeding of apple varieties with strong saline-alkali resistance. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01333-5.

Dietary supplementation with probiotics increases growth performance, improves the intestinal mucosal barrier and activates the Wnt/ß-catenin pathway activity in chicks.

BACKGROUND: Probiotics comprise effective feed additives that can replace antibiotics in animal livestock production. However, mono-strain probiotics appear less effective because of their instability. Therefore, the present study aimed to investigate dietary supplementation with compound probiotics (CPP) on growth performance, diarrhea rate and intestinal mucosal barrier, as well as the possible molecular mechanism, in chicks. In total, 360 1-day-old chicks of the Hy-Line Brown Chicks were randomly divided into the control group (CON, basal diet), chlortetracycline group (500 mg kg-1 CTC) and compound probiotics group (1000 mg kg-1 CPP, consisting of Bacillus subtilis, Bacillus licheniformis, Enterococcus faecium and yeast). The experiment period was 56 days. RESULTS: The results showed that, in comparison with the CON group, CPP significantly increased the average daily feed intake and average daily gain of chicks and reduced diarrhea (P < 0.05). The probiotic group exhibited increased immune organ (i.e. spleen and thymus) mass and increased levels of serum immunoglobulin (Ig)A, IgM and IgG (P < 0.05) compared to the CTC group. In addition, the jejunal mass and morphology were improved in the probiotic group (P < 0.05). Moreover, CPP reinforced jejunal barrier function, as indicated by increased transepithelial electrical resistance, protein expression of occludin and claudin-1, and diamine oxidase levels in the jejunum (P < 0.05). Likewise, enhanced fluorescence signals of proliferating cell nuclear antigen-labeled mitotic cells and villin-labeled absorptive cells in the jejunum (P < 0.05) suggested that CPP promoted intestinal stem cells activity. Mechanistically, the Wnt/ß-catenin signaling pathway, including ß-catenin, TCF4, c-Myc, cyclin D1 and Lgr5, was amplified in the jejunum by CPP addition (P < 0.05). CONCLUSION: The present study demonstrated that dietary supplementation with CPP reinforced the jejunal epithelial integrity by activating Wnt/ß-catenin signaling and enhanced immune function in chicks. © 2023 Society of Chemical Industry.

Influence of Chronic Nitrate-Rich Beetroot Juice Supplementation on the Endurance Performance of Active Winter Triathletes: A Randomized Controlled Trial.

OBJECTIVE: The impact of high-nitrate beetroot juice (BRJ) supplementation has seen a recent explosion of interest in sports science. This study examined the potential influence of 7-day BRJ supplementation on the endurance performance of winter triathletes. METHODS: Eighty young active winter triathletes (44 males, age = 21.50 ± 1.15 yrs; 36 females, age = 20.66 ± 1.45 yrs) participated in this study and were provided with either BRJ (6.5 mmol NO3-/70 mL) or a placebo (PL, 0.065 mmol NO3-/70 mL) for 7 days (a dose of ×3 per day) in a randomized, double-blind design. The athletes then completed a submaximal treadmill run, intraday cycling exhaustion testing, and a 10-km cross country (XC) skiing competition on the second day. RESULTS: There was a significant decrease in the oxygen uptake, respiratory exchange ratio, and blood lactic acid level (p < 0.05) between the BRJ and PL treatment groups during V3 speed running (males: 13.3 km·h-1, females: 11.6 km·h-1). BRJ treatment also remarkably increased the time to exhaustion (TTE) during cycling exhaustion testing (males: p = 0.02, females: p = 0.04). No significant differences were observed in medium- or low-speed submaximal treadmill runs and 10-km XC skiing performance. CONCLUSIONS: One week of daily nitrate-rich BRJ supplementation improved running economy at high speed during the submaximal treadmill running test and extended the TTE of athletes during cycling exhaustion testing. However, BRJ supplementation did not improve the performance in 10-km on-snow time trials in XC skiing. Regarding nutritional strategies to improve endurance performance in exercise training and competition, these results should be carefully considered owing to the different motor skill levels and competitive abilities of participants.

Ji-Chuan decoction ameliorates slow transit constipation via regulation of intestinal glial cell apoptosis.

BACKGROUND: Slow transit constipation (STC) is a common intestinal disease with increasing incidence. STC results from various factors, such as the enteric nervous system and metabolic changes. As a classical formula of traditional Chinese medicine, Ji-Chuan decoction (JCD) has been extensively and effectively used in STC treatment, yet its pharmacological mechanism remains unclear. AIM: To explore the integrated regulatory pattern of JCD against STC through hyphenated techniques from metabolism, network pharmacology and molecular methods. METHODS: STC model mice were generated by intragastric administration of compound diphenoxylate (10 mg/kg/d) for 14 d. The STC mice in the low dose of JCD (3.04 g/kg), middle dose of JCD (6.08 g/kg) and high dose of JCD (12.16 g/kg) groups were orally administered JCD solution once a day for 2 wk. The acetylcholine (ACH) level was examined by enzyme-linked immunosorbent assay. The pathological features of colon tissue were observed by hematoxylin and eosin staining. The differentially expressed metabolites and metabolic pathways were tested by nontargeted metabolomics. The main targets and core ingredients of JCD were identified by network pharmacology, and the expression of AKT was confirmed by immunohistochemistry. Finally, the pathways involved in JCD treatment were predicted using a combination of differentially expressed metabolites and targets, and intestinal glial cell apoptosis was demonstrated by immunofluorescence. RESULTS: JCD significantly promoted intestinal motility, increased the levels of the excitatory neurotransmitter ACH and reduced intestinal inflammation in STC mice. Untargeted metabolomics results showed that JCD significantly restored metabolic dysfunction and significantly affected taurine and hypotaurine metabolism. Network pharmacology and molecular experiments showed that JCD regulates AKT protein expression, and the core component is quercetin. Combined analysis demonstrated that apoptosis may be an important mechanism by which JCD relieves constipation. Further experiments showed that JCD reduced enteric glial cell (EGC) apoptosis. CONCLUSION: This work demonstrated that reducing EGC apoptosis may be the critical mechanism by which JCD treats STC. These findings call for further molecular research to facilitate the clinical application of JCD.

L-glutamate requires ß-catenin signalling through Frizzled7 to stimulate porcine intestinal stem cell expansion.

Intestinal stem cells (ISCs) decode and coordinate various types of nutritional information from the diet to support the crypt-villus axis architecture, but how specific dietary molecules affect intestinal epithelial homeostasis remains unclear. In the current study, L-glutamate (Glu) supplementation in either a nitrogen-free diet (NFD) or a corn-soybean meal diet (CSMD) stimulated gut growth and ISC expansion in weaned piglets. Quantitative proteomics screening identified the canonical Wnt signalling pathway as a central regulator of intestinal epithelial development and ISC activity in vivo. Importantly, the Wnt transmembrane receptor Frizzled7 (FZD7) was upregulated in response to dietary Glu patterns, and its perturbations in intestinal organoids (IOs) treated with a specific inhibitor and in FZD7-KO IPEC-J2 cells disrupted the link between Glu inputs and ß-catenin signalling and a subsequent reduction in cell viability. Furthermore, co-localization, coimmunoprecipitation (Co-IP), isothermal titration calorimetry (ITC), and microscale thermophoresis (MST) revealed that Glu served as a signalling molecule directly bound to FZD7. We propose that FZD7-mediated integration of the extracellular Glu signal controls ISC proliferation and differentiation, which provides new insights into the crosstalk of nutrients and ISCs.

[Preparation of salvianolic acid B, tanshinone â ¡_A, and glycyrrhetinic acid lipid emulsion and its protective effect against acute liver injury induced by acetaminophen].

Salvianolic acid B(Sal B), tanshinone Ⅱ_A(TSN Ⅱ_A), and glycyrrhetinic acid(GA) lipid emulsion(GTS-LE) was prepared by the high-speed dispersion method combined with ultrasonic emulsification.The preparation process of the emulsion was optimized by single-factor method and D-optimal method with appearance, centrifugal stability, and particle size of the emulsion as evalua-tion indexes, followed by verification.In vitro release of Sal B, TSN Ⅱ_A, and GA in GTS-LE was performed by reverse dialysis.In vivo pharmacokinetic evaluation was carried out in mice.The acute liver injury model was induced by acetaminophen.The effect of oral GTS-LE on the acute liver injury was investigated by serum liver function indexes and pathological changes in liver tissues of mice.The results showed that under the optimal preparation process, the average particle size of GTS-LE was(145.4±9.25) nm and the Zeta potential was(-33.6±1.45) mV.The drug-loading efficiencies of Sal B, TSN Ⅱ_A, and GA in GTS-LE were above 95%, and the drug release in vitro conformed to the Higuchi equation.The pharmacokinetic results showed that the C_(max) of Sal B, TSN Ⅱ_A, and GA in GTS-LE was 3.128, 2.7, and 2.85 times that of the GTS-S group, and AUC_(0-t) of Sal B, TSN Ⅱ_A, and GA in GTS-LE was 3.09, 2.23, and 1.9 times that of the GTS-S group.After intragastric administration of GTS-LE, the activities of alanine aminotransferase and aspartate aminotransferase were significantly inhibited, the content of malondialdehyde was reduced, and the structure of hepatocytes recovered to normal.In conclusion, GTS-LE can delay the release of Sal B and promote the release of TSN Ⅱ_A and GA.The encapsulation of three drug components in the emulsion can improve the oral bioavailability to varying degrees and can effectively prevent the acute liver injury caused by acetaminophen.

[Effect of light intensity on growth, accumulation of ginsenosides, and expression of related enzyme genes of Panax quinquefolius].

Appropriate light intensity is favorable for the photosynthesis, biomass accumulation, key enzyme activity, and secondary metabolite synthesis of medicinal plants. This study aims to explore the influence of light intensity on growth and quality of Panax quinquefolius. To be specific, sand culture experiment was carried out in a greenhouse under the light intensity of 40, 80, 120, and 160 µmol·m~(-2)·s~(-1), respectively. The growth indexes, photosynthetic characteristics, content of 6 ginsenosides of the 3-year-old P. quinquefolius were determined, and the expression of ginsenoside synthesis-related enzyme genes in leaves, main roots, and fibrous roots was determined. The results showed that the P. quinquefolius growing at 80 µmol·m~(-2)·s~(-1) light intensity had the most biomass and the highest net photosynthetic rate. The total biomass of P. quinquefolius treated with 120 µmol·m~(-2)·s~(-1) light intensity was slightly lower than that with 80 µmol·m~(-2)·s~(-1). The root-to-shoot ratio in the treatment with 120 µmol·m~(-2)·s~(-1) light intensity was up to 6.86, higher than those in other treatments(P<0.05),and the ginsenoside content in both aboveground and underground parts of P. quinquefolius in this treatment was the highest, which was possibly associated with the high expression of farnesylpyrophosphate synthase(FPS), squalene synthase(SQS), squalene epoxidase(SQE), oxidosqualene cyclase(OSC), dammarenediol-Ⅱ synthase(DS), and P450 genes in leaves and SQE and DS genes in main roots. In addition, light intensities of 120 and 160 µmol·m~(-2)·s~(-1) could promote PPD-type ginsenoside synthesis in leaves by triggering up-regulation of the expression of upstream ginsenoside synthesis genes. The decrease in underground biomass accumulation of the P. quinquefolius grown under weak light(40 µmol·m~(-2)·s~(-1)) and strong light(160 µmol·m~(-2)·s~(-1)) was possibly attributed to the low net photosynthetic rate, stomatal conductance, and transpiration rate in leaves. In the meantime, the low expression of SQS, SQE, OSC, and DS genes in the main roots might led to the decrease in ginsenoside content. However, there was no significant correlation between the ginsenoside content and the expression of synthesis-related genes in the fibrous roots of P. quinquefolius. Therefore, the light intensity of 80 and 120 µmol·m~(-2)·s~(-1) is beneficial to improving yield and quality of P. quinquefolius. The above findings contributed to a theoretical basis for reasonable shading in P. quinquefolius cultivation, which is of great significance for improving the yield and quality of P. quinquefolius through light regulation.

[Effect of acupuncture and moxibustion on skin barrier function in guinea pigs with eczema of skin damp-heat accumulation].

OBJECTIVE: To observe the effect of acupuncture and moxibustion on the water content of stratum corneum (WCSC), expression of serum inflammatory factors and aquaporin 3 (AQP3) in skin, lung and rectum in guinea pigs with eczema of skin damp-heat accumulation, and to explore the possible mechanism of acupuncture and moxibustion for regulating skin barrier function. METHODS: A total of 24 male albino guinea pigs were randomly divided into a blank group (n=6) and a modeling group (n=18). The guinea pigs in the modeling group were induced by 2,4-dinitrochlorobenzene (DNCB) to establish the eczema model of skin damp-heat accumulation. The guinea pigs with successful modeling were further randomly divided into a model group, a medication group and an acupuncture-moxibustion group, 6 guinea pigs in each group. The guinea pigs in the medication group were treated with loratadine tablets (0.8 mg/kg) by gavage, once a day for 7 days; the guinea pigs in the acupuncture-moxibustion group were treated with acupuncture at "Feishu" (BL 13), "Pishu" (BL 20), "Quchi" (LI 11), "Zusanli" (ST 36) and "Xuehai" (SP 10); at the same time, moxibustion was applied at "Feishu" (BL 13) and "Zusanli" (ST 36), moxibustion intervention for 10 min and needle retaining for 15 min at each acupoint, once a day for 7 days. The eczema area and severity index (EASI) score was evaluated before and After intervention, and WCSC and trans-epidermal water loss (TEWL) were measured by skin tester. After intervention, The HE staining was used to observe the changes of skin histomorphology in each group; ELISA was used to measure the contents of serum immunoglobulin E (IgE), interleukin (IL)-4 and IL-17; Western blot was used to measure the protein expression of AQP3 in skin, lung and rectum. RESULTS: Before the intervention, compared with the blank group, the EASI scores and TEWL were increased in the remaining groups (P<0.01), and the WCSC was decreased (P<0.01). After the intervention, compared with the model group, the EASI scores and TEWL were decreased (P<0.05, P<0.01), and WCSC was increased (P<0.01) in the medication group and the acupuncture-moxibustion group. The epidermal structure in the blank group was complete and the fibers in the dermis were arranged orderly; in the model group, epidermal hyperkeratosis, proliferation of granular layer, spinous cell layer and basal layer, and disordered arrangement of dermal fibers and infiltration of inflammatory cells were observed. The morphological performance in the medication group and the acupuncture-moxibustion group was better than that in the model group. Compared with the blank group, the contents of serum IgE and IL-17 were increased (P<0.01), and the content of serum IL-4 and the protein expression of AQP3 in skin, lung and rectum were decreased in the model group (P<0.01, P<0.05). Compared with the model group, the contents of serum IgE and IL-17 were decreased and the contents of serum IL-4 were increased in the medication group and the acupuncture-moxibustion group (P<0.01), and the protein expression of AQP3 in skin, lung and rectum in the acupuncture- moxibustion group were increased (P<0.05). Compared with the medication group, the contents of serum IgE and IL-17 were increased (P<0.01), and the content of serum IL-4 was decreased (P<0.01) in the acupuncture-moxibustion group. CONCLUSION: Acupuncture and moxibustion could improve the epidermal water metabolism and skin tissue morphology in guinea pigs with eczema of skin damp-heat accumulation. Its mechanism may be related to regulating inflammatory factors, up-regulating the expression of AQP3, and then repairing the skin barrier function.

Ascyrones A-E, type B bicyclic ployprenylated acylphloroglucinol derivatives from Hypericum ascyron.

Five new polycyclic polyprenylated acylphloroglucinols (1-5), ascyrones A-E, and four known compounds (6-9) were isolated from the aerial parts of Hypericum ascyron. All of the isolates containing a bicyclo[3.3.1]nonane-2,4,9-trione core and a benzoyl group, belonged to type B bicyclic polyprenylated acylphloroglucinols (BPAPs). Their structures and absolute configurations were established based on spectroscopic analyses and calculated electronic circular dichroism (ECD) data. The anti-inflammatory, neuroprotective and cytotoxicity activities of compounds 1-4 and 6-9 were evaluated. Compound 6 exhibited obvious anti-inflammatory activity in lipopolysaccharide (LPS)-induced RAW264.7 cells. Compounds 1 and 9 exhibited slight cytotoxicity against Hep3B cells. Meanwhile, compound 1 showed mild neuroprotective activity against corticosterone (CORT)-induced PC12 cell damage at 10 µmol·L-1.

The Efficacy of Senna Bowel Preparation for Colonoscopy: A Systematic Review and Meta-analysis.

The quality of bowel preparation is an extremely important determinant of colonoscopy results. However, the efficacy of senna regimens in improving bowel cleanliness is uncertain. We conducted a systematic review and meta-analysis to synthesize data on whether using a senna bowel preparation regimen enhances the bowel cleanliness. We searched Web of Science Core Collection, MEDLINE, PubMed, Embase, Cochrane Library, and Scopus databases (from the inception to August 2021). The primary efficacy outcome was bowel cleanliness. Secondary outcomes included patient compliance, tolerance, and adverse events. Eleven trials fulfilled the inclusion criteria (3,343 patients. Overall, we found no significant differences in bowel cleanliness between the senna regimen and other bowel preparation regimens (odds ratio [95% confidence interval]: 1.02 [0.63, 1.67], p = 0.93). There was significant difference in tolerance (odds ratio [95% confidence interval]: 1.66 [1.08, 2.54], p = .02) and compliance (odds ratio [95% confidence interval]: 3.05 [1.42, 6.55], p = .004). The senna regimen yielded a significantly greater proportion of no nausea (odds ratio [95% confidence interval]: 1.84 [1.45, 2.32]) and vomiting (odds ratio [95% confidence interval]: 1.65 [0.81, 3.35]). Compared with other bowel preparation regimens, the senna regimen may be effective and safe in bowel cleaning before colonoscopy, with superior compliance and tolerance.

[Preparation of tanshinone â ¡_A-glycyrrhetinic acid solid lipid nanoparticles and its inhibitory effect on acne].

The optimal prescription of tanshinone Ⅱ_A(TSN)-glycyrrhetinic acid(GA) solid lipid nanoparticles(GT-SLNs) was explored and evaluated in vivo and in vitro, and its effect on acne after oral administration was investigated. The preparation processing and prescription were optimized and verified by single factor and response surface methodology. The in vitro release of GA and TSN in GT-SLNs was determined by ultra-performance liquid chromatography(UPLC). The effect of GT-SLNs on acne was investigated by the levels of sex hormones in mice, ear swelling model, and tissue changes in sebaceous glands, and the pharmacokinetics was evaluated. The 24-hour cumulative release rates of GA and TSN in SLNs were 65.87%±5.63% and 36.13%±2.31% respectively. After oral administration of GT-SLNs and the mixture of GA and TSN(GT-Mix), the AUC_(0-t) and AUC_(0-∞) of TSN in GT-SLNs were 1.98 times and 4.77 times those in the GT-Mix group, respectively, and the peak concentration of TSN in the GT-SLNs group was 17.2 times that in the GT-Mix group. After intragastric administration of GT-SLNs, the serum levels of testosterone(T) and the ratio of testosterone to estradiol(T/E2) in the GT-SLNs group significantly declined, and the sebaceous glands of mice were atrophied to a certain extent. The results demonstrated that obtained GT-SLNs with good encapsulation efficiency and uniform particle size could promote the release of GA and TSN. GT-SLNs displayed therapeutic efficacy on acne manifested by androgen increase, abnormal sebaceous gland secretion, and inflammatory damage.

Preconcentration of liposoluble constituents in Salvia Miltiorrhiza using acid-assisted liquid phase microextraction based on a switchable deep eutectic solvent.

A switchable deep eutectic solvent-based liquid-phase microextraction was proposed and applied to the preconcentration and determination of liposoluble quality-markers of diterpenoid quinones (dihydrotanshinone I, cryptotanshinone, tanshinone I, and tanshinone IIA) in traditional Chinese medicine coupled with high performance liquid chromatography-ultraviolet detection. In the procedure, the hydrophilic deep eutectic solvent of diethanolamine-hexanoic acid (molar ratio 1:1) was prepared and added into the sample phase as an extractant, and a homogeneous solution was formed under slight vortex stirring. After the addition of HCl solution, the deep eutectic solvent miscible with the sample phase was converted to hydrophobic form, and a cloudy solution was generated. Then, the upper hydrophobic layer enriching the target analytes was collected through centrifugation for high performance liquid chromatography analysis. Several critical parameters affecting the extraction performance including the composition and consumption of switchable deep eutectic solvent, the type and amount of acid, salt amount and extraction time were investigated and optimized. Moreover, the structures of the deep eutectic solvent and the recovered hydrophobic layer were both characterized using Fourier transform infrared spectroscopy, further demonstrating the switching mechanism of the extractant during the extraction process. Under the optimal conditions, enrichment factors of diterpenoid quinones ranged from 59 to 274. Good linearities (r≥0.9963), low detection limits (0.5-0.7 ng/mL), satisfactory precisions (relative standard deviations 0.5%-8.6%) and accuracies (recoveries 94.6%-104.6%) were also obtained. Comparing the proposed switchable deep eutectic solvent-based liquid-phase microextraction with other published methods, the characteristics of the procedure were summarized. The developed method was successfully applied for the preconcentration of four liposoluble diterpenoid quinones from a traditional Chinese herbal medicine of Salvia Miltiorrhiza.

The Impact of ZIP8 Disease-Associated Variants G38R, C113S, G204C, and S335T on Selenium and Cadmium Accumulations: The First Characterization.

The metal cation symporter ZIP8 (SLC39A8) is a transmembrane protein that imports the essential micronutrients iron, manganese, and zinc, as well as heavy toxic metal cadmium (Cd). It has been recently suggested that selenium (Se), another essential micronutrient that has long been known for its role in human health and cancer risk, may also be transported by the ZIP8 protein. Several mutations in the ZIP8 gene are associated with the aberrant ion homeostasis of cells and can lead to human diseases. However, the intricate relationships between ZIP8 mutations, cellular Se homeostasis, and human diseases (including cancers and illnesses associated with Cd exposure) have not been explored. To further verify if ZIP8 is involved in cellular Se transportation, we first knockout (KO) the endogenous expression of ZIP8 in the HeLa cells using the CRISPR/Cas9 system. The elimination of ZIP8 expression was examined by PCR, DNA sequencing, immunoblot, and immunofluorescence analyses. Inductively coupled plasma mass spectrometry indicated that reduced uptake of Se, along with other micronutrients and Cd, was observed in the ZIP8-KO cells. In contrast, when ZIP8 was overexpressed, increased Se uptake could be detected in the ZIP8-overexpressing cells. Additionally, we found that ZIP8 with disease-associated single-point mutations G38R, G204C, and S335T, but not C113S, showed reduced Se transport ability. We then evaluated the potential of Se on Cd cytotoxicity prevention and therapy of cancers. Results indicated that Se could suppress Cd-induced cytotoxicity via decreasing the intracellular Cd transported by ZIP8, and Se exhibited excellent anticancer activity against not all but only selected cancer cell lines, under restricted experimental conditions. Moreover, clinical-based bioinformatic analyses revealed that up-regulated ZIP8 gene expression was common across multiple cancer types, and selenoproteins that were significantly co-expressed with ZIP8 in these cancers had been identified. Taken together, this study concludes that ZIP8 is an important protein in modulating cellular Se levels and provides insights into the roles of ZIP8 and Se in disease prevention and therapy.

[Textual research on classical prescriptions in Mongolian medicine].

Mongolians have a long history of using prescriptions, which can be classified into four stages as follows: the germination and experience accumulation stage before the 13 th century, the theoretical formation stage from the 13 th to 16 th century, the rapid development stage from the 17 th to 20 th century, and the leaping development stage from the mid-20 th century to the present. The prescriptions from the ancient classical or representative medical books have always been used by Mongolian physicians for generations, and they are still in use due to the definite curative effects. In 2008, the Notice on Issuing the Supplementary Provisions to the Registration and Management of Traditional Chinese Medicine(TCM) described that China has attached more importance to the excavation and development of classical prescriptions. As stipulated in the Law of the People's Republic of China on Traditional Chinese Medicine, the classical prescriptions should be those available in ancient TCM classics and still in wide use, with exact curative effects, distinct features, and obvious advantages. This paper expounded the historical formation and development of classical prescriptions in Mongo-lian medicine, introduced the five most influential ancient medical books revealing the formation and development of these classic prescriptions, and traced the origin of such classical prescriptions as Wenguanmu Siwei Decoction, Shouzhangshen Bawei Decoction, Jianghuang Siwei Decoction and summarized the origin, development history and characteristics of classical prescriptions in Mongolian medicine, aiming to provide a reference for their further research and development.

Pseudolaric Acid B Attenuates High Salt Intake-Induced Hypertensive Left Ventricular Remodeling by Modulating Monocyte/Macrophage Phenotypes.

BACKGROUND Studies in ApoE knockout mice have shown that pseudolaric acid B (PB) can act as an immunomodulatory drug and attenuate atherosclerosis progression by modulating monocyte/macrophage phenotypes. Our previous study demonstrated that high salt intake could shift the phenotype of monocytes/macrophages to an inflammatory phenotype, and that this shift was related to hypertension and hypertensive left ventricular (LV) remodeling. However, no comprehensive assessment of the effects of PB on hypertensive LV remodeling has been conducted. MATERIAL AND METHODS In this study, RAW264.7 macrophages cultured with different concentrations of NaCl were used to investigate the modulating effects of PB on macrophage phenotype. Furthermore, N-nitro-L-arginine methyl ester hypertensive mice were used to investigate the modulating effects of PB on monocyte phenotype. LV remodeling was investigated by echocardiography. LV morphologic staining (for cardiomyocyte hypertrophy and collagen deposition) was performed at the time of sacrifice. RESULTS The results showed that PB significantly improved the viability of RAW264.7 cells, suppressed their phagocytic and migration abilities, and inhibited their phenotypic shift to M1 macrophages. In addition, the blood pressure of PB-treated mice was significantly decreased relative to that of control mice. Furthermore, after PB treatment, the percentage of Ly6Chi monocytes was significantly decreased while that of Ly6Clo monocytes was apparently increased. Moreover, PB preserved LV function and alleviated myocardial fibrosis and cardiomyocyte hypertrophy as measured at the end of the experimental period. The transfer of monocytes from PB-treated mice to hypertensive mice achieved the same effects. CONCLUSIONS Together, these findings indicate that PB exerts its protective effects on hypertensive LV remodeling by modulating monocyte/macrophage phenotypes and warrants further investigation.

Gut dysbiosis correction contributes to the hepatoprotective effects of Thymus quinquecostatus Celak extract against alcohol through the gut-liver axis.

Alcoholic liver disease (ALD) is a major health issue globally due to the consumption of alcoholic beverages. Thymus quinquecostatus Celak is a food additive and an edible herb that is widely used in Asia and possesses hepatoprotective activity, but the underlying mechanisms behind this protective activity are not completely understood. The purpose of this study was to investigate the hepatoprotective effects of Thymus quinquecostatus Celak extract (TQE) against ALD as well as the underlying mechanism based on gut microbiota and the gut-liver axis. TQE supplementation markedly alleviated chronic alcohol-induced liver injury in C57 mice. TQE also ameliorated gut barrier dysfunction induced by alcohol. Consequently, the activation of the lipopolysaccharide (LPS) translocation-mediated TLR4 pathway and the subsequent inflammatory response and ROS overproduction in the liver were suppressed. Meanwhile, alcohol-induced gut microbiota dysbiosis was also corrected by TQE. To further investigate the contribution of gut dysbiosis correction to the beneficial effects of TQE on ALD, a fecal microbiota transplantation study was conducted. TQE-manipulated gut microbiota transplantation markedly counteracted the alcohol-induced gut dysbiosis in the recipient mice. In parallel with gut dysbiosis correction, liver damage was partly ameliorated in the recipient mice. Gut barrier dysfunction, endotoxemia, TLR4 pathway induction as well as downstream inflammatory response and ROS overproduction were also partly suppressed due to gut dysbiosis correction in alcohol-fed recipient mice. In summary, these results suggest that gut dysbiosis correction contributes to the hepatoprotective effects of TQE against alcohol through the gut-liver axis.