Brachial plexopathy following stereotactic body radiation therapy in apical lung malignancies: A dosimetric pooled analysis of individual patient data.

BACKGROUND AND OBJECTIVES: The aim of this study is to establish dosimetric constraints for the brachial plexus at risk of developing grade ≥ 2 brachial plexopathy in the context of stereotactic body radiation therapy (SBRT). PATIENTS AND METHODS: Individual patient data from 349 patients with 356 apical lung malignancies who underwent SBRT were extracted from 5 articles. The anatomical brachial plexus was delineated following the guidelines provided in the atlases developed by Hall, et al. and Kong, et al.. Patient characteristics, pertinent SBRT dosimetric parameters, and brachial plexopathy grades (according to CTCAE 4.0 or 5.0) were obtained. Normal tissue complication probability (NTCP) models were used to estimate the risk of developing grade ≥ 2 brachial plexopathy through maximum likelihood parameter fitting. RESULTS: The prescription dose/fractionation schedules for SBRT ranged from 27 to 60 Gy in 1 to 8 fractions. During a follow-up period spanning from 6 to 113 months, 22 patients (6.3 %) developed grade ≥2 brachial plexopathy (4.3 % grade 2, 2.0 % grade 3); the median time to symptoms onset after SBRT was 8 months (ranged, 3-54 months). NTCP models estimated a 10 % risk of grade ≥2 brachial plexopathy with an anatomic brachial plexus maximum dose (Dmax) of 20.7 Gy, 34.2 Gy, and 42.7 Gy in one, three, and five fractions, respectively. Similarly, the NTCP model estimates the risks of grade ≥2 brachial plexopathy as 10 % for BED Dmax at 192.3 Gy and EQD2 Dmax at 115.4 Gy with an α/ß ratio of 3, respectively. Symptom persisted after treatment in nearly half of patients diagnosed with grade ≥2 brachial plexopathy (11/22, 50 %). CONCLUSIONS: This study establishes dosimetric constraints ranging from 20.7 to 42.7 Gy across 1-5 fractions, aimed at mitigating the risk of developing grade ≥2 brachial plexopathy following SBRT. These findings provide valuable guidance for future ablative SBRT in apical lung malignancies.

HBV promotes its replication by up-regulating RAD51C gene expression.

Chronic hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC), pegylated-interferon-α(PEG-IFNα) and long-term nucleos(t)ide analogs (NUCs) are mainly drugs used to treat HBV infection, but the effectiveness is unsatisfactory in different populations, the exploration of novel therapeutic approaches is necessary. RAD51C is associated with DNA damage repair and plays an important role in the development and progression of tumors. Early cDNA microarray results showed that RAD51C expression was significantly increased in HBV-infected HCC cells, however, the relationship between HBV infection and abnormal expression of RAD51C has not been reported. Therefore, we conducted RT-PCR, western blot, Co-immunoprecipitation(Co-IP), and immunofluorescence(IF) to detect HBV-RAD51C interaction in RAD51C overexpression or interfering HCC cells. Our results showed that RAD51C and HBV X protein(HBX) produced a direct interaction in the nucleus, the HBV infection of HCC cells promoted RAD51C expression, and the increased expression of RAD51C promoted HBV replication. This indicated that RAD51C is closely related to the occurrence and development of HCC caused by HBV infection, and may bring a breakthrough in the the prevention and treatment study of HCC.

YuPingFeng (YPF) upregulates caveolin-1 (CAV1) to alleviate pulmonary fibrosis through the TGF-ß1/Smad2 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) is considered a valuable asset in China's medical tradition. YPF is a classic prescription that has been derived from the "Jiu Yuan Fang" formula and consists of three herbs: Huangqi (Astragalus membranaceus Bunge), Baizhu (Atractylodes rubra Dekker), and Fangfeng (Saposhnikovia divaricata (Turcz.) Schischk). This prescription is widely acclaimed for its exceptional pharmacological properties, including potent antioxidant effects, hormone regulation, and immune modulation effects. AIM OF THE STUDY: Previous research provides evidence suggesting that YPF may have therapeutic effects on pulmonary fibrosis. Further exploration is essential to confirm its effectiveness and elucidate the fundamental processes. MATERIALS AND METHODS: First, the active components and target genes of YPF were extracted from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Next, the GSE53845 dataset, which contains information on pulmonary fibrosis, was downloaded from the GEO database. Network informatics methods was then be utilized to identify target genes associated with pulmonary fibrosis. A YPF-based network of protein-protein interactions was constructed to pinpoint possible target genes for pulmonary fibrosis treatment. Additionally, an in vitro model of pulmonary fibrosis induced by bleomycin (BLM) was established to further investigate and validate the possible mechanisms underlying the effectiveness of YPF. RESULTS: In this study, a total of 24 active ingredients of YPF, along with 178 target genes associated with the treatment, were identified. Additionally, 615 target genes related to pulmonary fibrosis were identified. Functional enrichment analysis revealed that 18 candidate genes (CGs) exhibited significant responses to tumor necrosis factor, NF-kB survival signaling, and positive regulation of apoptosis processes. Among these CGs, CAV1, VCAM1, and TP63 were identified as key target genes. Furthermore, cell experiments confirmed that the expression of CAV1 protein and RNA expression was increased in pulmonary fibrosis, but significantly decreased after treatment with YPF. Additionally, the expression of pSmad2, α-SMA, TGF-ß1, and TNF-α was also decreased following YPF treatment. CONCLUSIONS: Network pharmacology analysis revealed that YPF exhibits significant potential as a therapeutic intervention for pulmonary fibrosis by targeting various compounds and pathways. This study emphasizes that the efficacy of YPF in treating pulmonary fibrosis may be attributed to its ability to up-regulate CAV1 expression and inhibiting pulmonary fibrosis via modulation of the TGF-ß1/Smad2 signaling pathway. These findings underscore the promising role of YPF and its ability to potentially alleviate pulmonary fibrosis.

Lysosomal control of dendritic cell function.

Lysosomal compartments undergo extensive remodeling during dendritic cell (DC) activation to meet the dynamic functional requirements of DCs. Instead of being regarded as stationary and digestive organelles, recent studies have increasingly appreciated the versatile roles of lysosomes in regulating key aspects of DC biology. Lysosomes actively control DC motility by linking calcium efflux to the actomyosin contraction, while enhanced DC lysosomal membrane permeability contributes to the inflammasome activation. Besides, lysosomes provide a platform for the transduction of innate immune signaling and the intricate host-pathogen interplay. Lysosomes and lysosome-associated structures are also critically engaged in antigen presentation and cross-presentation processes, which are pivotal for the induction of antigen-specific adaptive immune response. Through the current review, we emphasize that lysosome targeting strategies serve as vital DC-based immunotherapies in fighting against tumor, infectious diseases, and autoinflammatory disorders.

Quercetin serves as the major component of Xiang-lian Pill to ameliorate ulcerative colitis via tipping the balance of STAT1/PPARγ and dictating the alternative activation of macrophage.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese herbal formula, Xiang-lian Pill (XLP), is commonly prescribed for ulcerative colitis (UC) patients to relieve their clinical symptom. Nonetheless, the underlying cellular and molecular mechanisms of XLP's anti-UC effect remain incompletely understood. AIM OF THE STUDY: To evaluate the therapeutic effect and elucidate the possible working mechanisms of XLP in UC treatment. The major active component of XLP was also characterized. MATERIALS AND METHODS: Colitis was induced in C57BL/6 mice with 3% dextran sulfate sodium (DSS) dissolved in drinking water for 7 consecutive days. The UC mice were grouped and treated with XLP (3640 mg/kg) or vehicle orally during the procedure of DSS induction. Mouse body weight, disease activity index (DAI) score and colon length were recorded. Histopathological changes and inflammatory cell infiltration were evaluated by pathological staining and flow cytometric analysis (FACS). Network pharmacology, bioinformatic analysis, widely targeted and targeted metabolomics analysis were performed to screen the potential effective ingredients and key targets. Bone marrow derived macrophages (BMDMs), peripheral blood mononuclear cells (PBMCs), RAW264.7 and THP-1 cells were used to dissect the anti-inflammatory effect of XLP. RESULTS: Oral administration of XLP ameliorated DSS induced mouse colitis, as evidenced by reduced DAI and colonic inflammatory destruction. FACS results demonstrated that XLP treatment effectively restored immune tolerance in colon, inhibited the generation of monocyte derived macrophages and skewed macrophage polarization into M2 phenotype. Network pharmacology analysis suggested that innate effector modules related to macrophage activation comprise the major targets of XLP, and the counter-regulatory STAT1/PPARγ signaling possibly serves as the critical downstream pathway. Subsequent experiments unveiled an imbalance of STAT1/PPARγ signaling in monocytes derived from UC patients, and validated that XLP suppressed LPS/IFN-γ induced macrophage activation (STAT1 mediated) but facilitated IL-4 induced macrophage M2 polarization (PPARγ dependent). Meanwhile, our data showed that quercetin served as the major component of XLP to recapitulate the regulatory effect on macrophages. CONCLUSION: Our findings revealed that quercetin serves as the major component of XLP that regulates macrophage alternative activation via tipping the balance of STAT1/PPARγ, which provides a mechanistic explanation for the therapeutic effect of XLP in UC treatment.

Duloxetine for rehabilitation after total knee arthroplasty: a systematic review and meta-analysis.

OBJECTIVE: The aim was to evaluate the efficacy and safety of duloxetine for postoperative recovery after total knee arthroplasty. METHODS: The following electronic databases were searched for eligible trials: PubMed, EMBASE, Web of Science, Cochrane Library, VIP, Wanfang Data, and China National Knowledge Infrastructure (CNKI). The search was performed from the inception dates to 10 August 2022. Data extraction and quality assessment were performed by two independent reviewers. Standard mean differences or mean differences with 95% CIs for pooled data were calculated. The primary outcomes were pain, physical function, and analgesic consumption. Secondary outcomes included range of motion (ROM) of the knee, depression, and mental health. RESULTS: This meta-analysis included 11 studies, reporting on a total of 1019 patients. Results of analyses indicated that duloxetine showed a statistically significant reduction in pain at rest at 3 days, 1 week, 2, and 6 weeks and pain on movement at 5 days, 1 week, 2, 4, 6, and 8 weeks. However, there was no statistical significance in pain at rest and on movement at 24 h, 12 weeks, 6 months, and 12 months. Additionally, duloxetine had a significant improvement in physical function, ROM of the knee at 6 weeks, and emotional function (depression and mental health). Moreover, the cumulative opioid consumption at 24 h in the duloxetine groups was lower than in the control groups. But there was no statistical significance for the cumulative opioid consumption over 7 days between the duloxetine groups and controls. CONCLUSIONS: In conclusion, duloxetine might reduce pain mainly over a time span of 3 days-8 weeks and lower cumulative opioid consumption within 24 h. In addition, it improved physical function, ROM of the knee with a time span of 1-6 weeks and emotional function (depression and mental health).

Comparative analysis of pre- and postmenopausal endometrial cancer in 216 patients.

Background: Endometrial carcinoma (EC) is one of the most common gynecological malignancies and has become more prevalent in recent decades. The clinical manifestations and characteristics of EC in premenopausal and postmenopausal women differ and present with distinct pathological stages and subtypes of EC. Surgery remains the principal therapeutic approach, but the postoperative prognosis is largely affected by the pathological state. Methods: A retrospective study was conducted on 216 patients with EC who were hospitalized from August 2008 to August 2019 in Wuhan Union Hospital. The patients were divided into 2 groups based on the pre- or postmenopausal occurrence of EC. The general clinical characteristics, intraoperative situation, clinicopathological data, and postoperative outcomes of the 2 groups were compared. Results: Patients with premenopausal EC had earlier menarche, a higher incidence of primary infertility and anemia, and fewer pregnancies and deliveries. Patients with postmenopausal EC were older and often had hyperlipidemia and diabetes. Additionally, patients who were postmenopausal had worse tumor pathological gradings, more severe muscular invasion, and a higher rate of lymphatic metastasis. These factors led to a higher demand for postoperative radiotherapy in patients but a lower survival rate. Conclusions: Generally, premenopausal EC differs from postmenopausal EC: the latter is more malignant and has a worse prognosis.

A novel ATPase gene, Ab-atps, plays an important role in the interaction of rice and white tip nematode, Aphelenchoides besseyi.

Plant kinases containing the LysM domain play important roles in pathogen recognition and self-defense reactions. And it could recognize microbe-associated molecules including chitin and other polypeptides. The white tip nematode Aphelenchoides besseyi is a migratory parasitic nematode that infects plant shoots. It is distributed over almost all rice-producing areas and causes up to 50% economic losses. The rice OsRLK3 gene was a defense-related LysM kinase gene of rice. This study showed that the rice LysM kinase OsRLK3 could be induced by flg22, jasmonic acid, salicylic acid, and chitin. An interaction gene, Ab-atps from A. besseyi, was identified by screening the interaction between the rice gene OsRLK3 and an A. besseyi cDNA library using yeast two-hybrid screening. Ab-atps is a novel ATP synthase gene with a full length of 1341 bp, coding for 183 amino acids. The mRNA of Ab-atps was located in the esophagus and reproductive system of A. besseyi. The expression of Ab-atps was assessed at different developmental stages of the nematode and found to be the highest in the juvenile, followed by the egg, female, and male. Reproduction was significantly decreased in nematodes treated with Ab-atps double-stranded RNA (dsRNA) (p < 0.05). Transient expression experiments showed that Ab-ATPS-GFP was distributed in the nucleus, cytoplasm, and cell membrane, and Ab-ATPS-GFP triggered plant cell death. OsRLK3 was expressed significantly higher at 0.5 day and 1 day (p < 0.05) in rice plants inoculated with nematodes treated with Ab-atps dsRNA and gfp dsRNA for 0.5-7 days, respectively. Further, OsRLK3 expression under Ab-atps dsRNA treatment was significantly lower than with gfp dsRNA treatment at 0.5 day (p < 0.05) and significantly higher than with gfp dsRNA treatment at 1 day (p < 0.05). These results suggest that rice OsRLK3 could interact with A. besseyi Ab-atps, which plays an important role in growth, reproduction, and infection of the nematode. Our findings provide a theoretical basis to further understand the parasitic strategy of A. besseyi and its interaction mechanism with host plants, suggesting new ideas and targets for controlling A. besseyi.

GEO data mining and TCGA analysis reveal altered branched chain amino acid metabolism in pancreatic cancer patients.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor of the digestive system which has a less than 1% 5-year survival rate. The pathogenesis of PDAC development is incompletely understood. Genetic predisposition, disease history of chronic pancreatitis and diabetes elevate the risk of PDAC while environmental and dietary factors including smoking, alcohol abuse, high fat/protein intake as well as air pollution exacerbate PDAC progression. BCAAs, consisting of leucine, isoleucine and valine are essential amino acids that are obtained from food and play versatile roles in carcinogenesis. Recent studies have demonstrated that BCAA metabolism affects PDAC development but the results are controversial. To explore the possible engagement of BCAA metabolism in PDAC, we took advantage of the GEO and TCGA database and discovered that BCAA uptake is closely related to PDAC development while BCAA catabolism is down-regulated in PDAC tissue. Besides, NOTCH and MYC are differentially involved in BCAA metabolism in tumor and muscle, and enhanced lipid synthesis is independent of BCAA catabolism. Altogether, we highlight BCAA uptake as a promising target for PDAC treatment.

Resistin: Potential biomarker and therapeutic target in atherosclerosis.

Resistin, a cysteine-rich secretory protein, has a pleiotropic role in humans. Resistin usually presents as trimer or hexamer in plasma, and targets specific receptors Toll Like Receptor 4 (TLR4) or Adenylyl Cyclase-Associated Protein 1 (CAP1). Upon binding to TLR4 and CAP1, resistin can trigger various intracellular signal transduction pathways to induce vascular inflammation, lipid accumulation, and plaque vulnerability. These pro-atherosclerotic effects of resistin appear in various cell types, including endothelial cells, vessel smooth muscle cells and macrophages, which cause diverse damages to cardiovascular system from dyslipidemia, atherosclerosis rupture and ventricular remodeling. In this review, we gather recent evidence about the pro- atherosclerotic effects of resistin and highlight it as a candidate therapeutic or diagnostic target for cardiovascular disease.

Liraglutide Ameliorates Lipotoxicity-Induced Oxidative Stress by Activating the NRF2 Pathway in HepG2 Cells.

Although glucagon-like peptide-1 (GLP-1) analogue has been reported to suppress oxidative stress in non-alcoholic fatty liver disease (NAFLD), an effective therapeutic agent for NAFLD is currently unavailable. Therefore, in this study, we aimed to investigate the protective effects of the GLP-1 analogue liraglutide against lipotoxicity-induced oxidative stress in HepG2 cells and to elucidate the underlying mechanisms. HepG2 cells were cultured for 48 hours and treated with a free fatty acid (FFA) mixture: FFA mixture and liraglutide or FFA mixture, liraglutide, and exendin (9-39). Lipid accumulation was examined by oil red O staining. Oxidative stress was assessed by measuring the levels of intracellular reactive oxygen species using 2',7'-dichlorofluorescein diacetate and thiobarbituric acid-reactive substances, whereas antioxidant capacity was assessed by measuring the activity of superoxide dismutase and catalase. Expression of the nuclear factor erythroid-2-related factor 2 (NRF2) gene and the genes encoding antioxidant enzymes was analyzed using quantitative RT-PCR. Cellular and nuclear NRF2 expression levels were assessed using immunofluorescence cell staining and western blotting. Liraglutide treatment reduced high fat-induced lipid formation and the levels of oxidative stress markers and increased antioxidant enzyme activity in HepG2 cells. Liraglutide treatment increased the mRNA expression of NRF2 target genes, induced NRF2 nuclear translocation, and increased nuclear NRF2 levels without altering NRF2 mRNA expression. Collectively, these results indicate that liraglutide exhibits a protective effect against lipotoxicity-induced oxidative stress, possibly via modulation of NRF2 and expression of antioxidant enzymes in liver cells.

A Systematic Review Exploring the Anticancer Activity and Mechanisms of Glucomannan.

Glucomannan, long recognized as the active ingredient of the traditional Chinese medicinal herb Konjac glucomannan, is a naturally occurring polysaccharide existing in certain plant species and fungi. Due to its special property to also serve as a dietary supplement, glucomannan has been widely applied in clinic to lower body weight and circulation cholesterol level and to treat constipation, diabetes, and arterial sclerosis. Besides the regulatory role engaged with gastroenterological and metabolic syndrome, recently, its therapeutic effect and the underlying mechanisms in treating cancerous diseases have been appreciated by mounting researches. The present review aims to emphasize the multifaceted aspects of how glucomannan exerts its anti-tumor function.

BST1 rs4698412 allelic variant increases the risk of gait or balance deficits in patients with Parkinson's disease.

AIMS: We aimed to explore effects of bone marrow stromal cell antigen-1 (BST1) rs4698412 allelic variant on brain activation and associative clinical symptoms in Parkinson's disease (PD). METHODS: A total of 49 PD patients and 47 healthy control (HC) subjects were recruited for clinical evaluations, blood samples collection for genotypes, and resting-state functional MRI (rs-fMRI) scans. Based on BST1 rs4698412 allelic variant (G â†’ A), participants were further divided into 18 PD-GG, 31 PD-GA/AA, 20 HC-GG, and 27 HC-GA/AA carriers, which respectively indicated subjects carrying ancestral or risk allele in that locus in PD or HC. Two-way analysis of covariance (ANCOVA) was applied to investigate main effects and interactions between PD and BST1 rs4698412 allelic variant on brain function via amplitude of low-frequency fluctuations (ALFF). Spearman's correlations were then utilized to detect associations between interactive brain regions and clinical symptoms. RESULTS: Compared to HC subjects, PD patients exhibited increased ALFF values in left cerebellum_8 and cerebellum_9. Significant interaction was in right lingual gyrus, where there were the lowest ALFF values and ALFF values were only negatively associated with Timed Up and Go (TUG) test time in PD-GA/AA subgroup. CONCLUSION: BST1 rs4698412-modulated lingual gyrus functional alterations could be related to gait and balance dysfunction in PD.

Comparisons of antithrombosis, hematopoietic effects and chemical profiles of dried and rice wine-processed Rehmanniae Radix extracts.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine (TCM), Rehmanniae Radix (RR, derived from the root of Rehmannia glutinosa (Gaertn.) DC.) is commonly used as natural medicine for thousands of years, two types including the dried and rice-wine processed RR were used for different clinical purposes respectively, which were the typical case that pharmaceutical effect changed by processing in TCM. AIM OF STUDY: The goal of this study was to investigate the differences in the antithrombosis and hematopoietic effects of extracts of dried and processed RR (DRR and PRR) in vivo, and to explore the chemical basis underlying changes of medicinal properties caused by processing. MATERIALS AND METHODS: The aqueous extracts of DRR and PRR were prepared. Protective effect of varying doses of different extracts were investigated in type-I carrageenan induced mice tail thrombosis and cyclophosphamide induced myelosuppression model. The chemical composition of DRR and PRR extracts were determined by High Performance Liquid Chromatography coupled with tandem quadrupole time-of-flight Mass Spectrometry (HPLC/Q-TOF-MS). RESULTS: In antithrombosis activity tests, PRR possessed less ameliorated effects than DRR in the model mouse on body temperature, tail thrombus length and blood flow. Both DRR and PRR had no significant influence on prothrombin time (PT) and activated partial thromboplastin time (APTT), only high dose DRR could decrease the content of fibrinogen (FIB) in plasma. Histological examination of lung tissue suggested that thrombosis was significantly improved in DRR-H group. For myelosuppression model, only PRR could improve peripheral hemogram, both DRR and PRR had hematopoietic effects as demonstrated by their abilities to ameliorate the bone marrow nucleated cells (BMNC) and pathology of bone marrow tissue. The hematopoietic effects of PRR were significantly more potent than that of DRR at the concentration of 9 g/kg. By comparing the chemical composition, we found that iridoid glycosides were decreased and furfural derivatives increased in DRR after processing which may be the chemical mechanism contribute to the differences in efficacy. CONCLUSIONS: According to the results of this research, processing with rice wine for nine cycles significantly reduced antithrombotic effects and enhanced the hematopoietic effects of DRR as demonstrated in model mice. It can scientifically explain the different effect among two types of RR in clinical through the diverse method of processing and usage. Meanwhile, the predicted activity compounds from two types of RR can be potential candidates for the treatment of thrombosis and anemia.

Pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction in the liver of rats with severe acute pancreatitis.

AIM: To explore the pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction (DCQD) in the liver of rats with severe acute pancreatitis (SAP) based on an herbal recipe tissue pharmacology hypothesis. METHODS: Healthy male Sprague-Dawley rats were randomly divided into a sham operation group (SOG); a model group (MG); and low-, median- and high-dose treatment groups (LDG, MDG, and HDG, respectively). Different dosages (6, 12 and 24 g/kg for the LDG, MDG, and HDG, respectively) of DCQD were administered to the rats with SAP. The tissue concentrations of aloe-emodin, rhein, emodin, chrysophanol, honokiol, rheo chrysophanol, magnolol, hesperidin, naringenin and naringin in the liver of the treated rats were detected by high-performance liquid chromatography tandem mass spectrometry. Alanine transaminase (ALT) and aspartate transaminase (AST) in serum, inflammatory mediators in the liver and pathological scores were evaluated. RESULTS: The major components of DCQD were detected in the liver, and their concentrations increased dose-dependently. The high dose of DCQD showed a maximal effect in ameliorating the pathological damages, decreasing the pro-inflammatory mediators tumor necrosis factor-α and interleukin (IL)-6 and increasing anti-inflammatory mediators IL-4 and IL-10 in the liver. The pathological scores in the pancreas for the MG were significantly higher than those for the SOG (P < 0.05). DCQD could reduce the pathological scores in the pancreas and liver of the rats with SAP, especially in the HDG. Compared to the SOG, the ALT and AST levels in serum were higher in the MG (P < 0.05), while there was no statistical difference in the MG and HDG. CONCLUSION: DCQD could alleviate liver damage by altering the inflammatory response in rats with SAP based on the liver distribution of its components.

Pharmacokinetics and pharmacodynamics of Shengjiang decoction in rats with acute pancreatitis for protecting against multiple organ injury.

AIM: To explore the pharmacokinetics and pharmacodynamics of Shengjiang decoction (SJD) in rats with acute pancreatitis (AP) for protecting against multiple organ injury. METHODS: An AP model was established by retrograde perfusion of 3.5% sodium taurocholate into the biliopancreatic duct, and a control group (CG) received 0.9% sodium chloride instead. Twelve male Sprague-Dawley rats were randomly divided into a CG treated with SJD (CG + SJD) and a model group treated with SJD (MG + SJD), both of which were orally administered with SJD (5 g/kg) 2 h after surgery. Blood samples were collected via the tail vein at 10, 20, and 40 min and 1, 2, 3, 4, 6, 8, and 12 h after a single dose of SJD to detect its main components using high-performance liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters were compared. In the pharmacodynamic experiment, 18 male Sprague-Dawley rats were randomly divided into a CG, an AP model group (MG), and an SJD treated AP group (SJDG). Serum amylase, lipase, and inflammatory cytokines were measured, and heart, lung, liver, spleen, pancreas, kidney, and intestine tissues were collected for pathological examination. RESULTS: The MG + SJD displayed significantly shorter mean residence time (MRT) and higher clearance (CL) for emodin and aloe-emodin; significantly shorter time of maximum concentration and T1/2 and a lower area under curve (AUC) for aloe-emodin; a significantly higher AUC and lower CL for rhein; and longer MRT and lower CL for chrysophanol than the CG + SJD. In the pharmacodynamic experiment, the amylase, interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α levels in the MG were higher than those in the CG (P < 0.05). After the herbal decoction treatment, the SJDG had higher IL-10 and lower TNF-α levels than the MG (P < 0.05). The MG had the highest pathological scores, and the pathological scores of the lung, pancreas, kidney, and intestine in the SJDG were significantly lower than those in the MG (P < 0.05). CONCLUSION: AP may have varying effects on the pharmacokinetics of the major SJD components in rats. SJD might alleviate pathological injuries of the lung, pancreas, kidney, and intestine in rats with AP via regulating pro- and anti- inflammatory responses, which might guide the clinical application of SJD for AP treatment.

Effects of dietary fructooligosaccharide levels and feeding modes on growth, immune responses, antioxidant capability and disease resistance of blunt snout bream (Megalobrama amblycephala).

This study aimed to determine the effects of fructooligosaccharide (FOS) levels and its feeding modes on growth, immune response, antioxidant capability and disease resistance of blunt snout bream (Megalobrama amblycephala). Fish (12.5 ± 0.5 g) were subjected to three FOS levels (0, 0.4% and 0.8%) and two feeding modes (supplementing FOS continuously and supplementing FOS two days interval 5 days) according to a 3 × 2 factorial design. At the end of 8-week feeding trial, fish were challenged by Aeromonas hydrophila with concentration of 1 × 10(5) CFU mL(-1) and mortality was recorded for the next 96 h. Fish fed 0.4% FOS continuously (D2) and fish fed the basal diet for 5 days followed by 0.8% FOS for 2 days (D5) showed admirable growth performance. The highest plasma lysozyme, acid phosphatase and myeloperoxidase activities as well as complement component 3, total protein and immunoglobulin M (IgM) levels were all observed in fish fed D5. They were significantly higher (P < 0.05) than those of the control group and/or fish fed 0.8% FOS continuously, but exhibited no statistical difference (P > 0.05) with that of fish fed D2. A similar trend was also observed in antioxidant capability as well as the expression of Leap-I and Leap-Ⅱ. Mortality showed an opposite trend with the immune response with the lowest rate observed in fish fed D5. The results indicated that diet supplementing FOS in appropriate levels and feeding modes could improve the growth, immune response and antioxidant capability of fish, as might consequently lead to enhanced disease resistance. It can be speculated that the basal diet for 5 days followed by 0.8% FOS for 2 days was most suitable for blunt snout bream.